1 00:00:04,912 --> 00:00:09,349 SO GOOD MORNING AND WELCOME TO 2 00:00:09,349 --> 00:00:10,718 THE 2024 ANNUAL SICKLE CELL 3 00:00:10,718 --> 00:00:11,552 DISEASE RESEARCH MEETING. 4 00:00:11,552 --> 00:00:12,853 I'M JULIE PANEPINTO, DIRECTOR OF 5 00:00:12,853 --> 00:00:14,354 THE BLOOD DIVISION AT THE 6 00:00:14,354 --> 00:00:15,823 NATIONAL HEART, LUNG AND BLOOD 7 00:00:15,823 --> 00:00:16,824 INSTITUTE HERE AT THE NIH. 8 00:00:16,824 --> 00:00:18,358 I'M EXCITED TO KICK OFF THIS 9 00:00:18,358 --> 00:00:22,930 THREE-DAY MEETING AND WANT TO 10 00:00:22,930 --> 00:00:24,531 RECOGNIZE THE BEHIND THE SCENES 11 00:00:24,531 --> 00:00:35,542 WORK THAT.THIS TAKES A LOT OF PS 12 00:00:36,977 --> 00:00:37,978 YOU MIGHT IMAGINE. 13 00:00:37,978 --> 00:00:39,179 SO I THANK THEM FOR THEIR 14 00:00:39,179 --> 00:00:39,747 EFFORTS. 15 00:00:39,747 --> 00:00:41,849 SO THE NEXT FEW DAYS, WE'LL HEAR 16 00:00:41,849 --> 00:00:43,350 RESEARCH PRESENTED THAT FOCUSES 17 00:00:43,350 --> 00:00:46,420 ON KEY THINGS SHAPING THE 18 00:00:46,420 --> 00:00:47,554 LANDSCAPE OF SICKLE CELL 19 00:00:47,554 --> 00:00:47,955 DISEASE. 20 00:00:47,955 --> 00:00:50,891 TODAY WE'RE STARTING WITH A 21 00:00:50,891 --> 00:00:52,126 SYMPOSIUM ON CELL AND GENE 22 00:00:52,126 --> 00:00:53,961 THERAPIES AND OTHER THERAPEUTICS 23 00:00:53,961 --> 00:00:55,529 FOR SICKLE CELL DISEASE, WE'LL 24 00:00:55,529 --> 00:00:57,364 EXPLORE LATEST DEVELOPMENTS AND 25 00:00:57,364 --> 00:00:59,466 ALSO LEARNING HOW THESE 26 00:00:59,466 --> 00:01:00,434 THERAPIES IMPACT QUALITY OF LIFE 27 00:01:00,434 --> 00:01:02,002 AND PATIENT OUTCOMES. 28 00:01:02,002 --> 00:01:05,239 TOMORROW WE WILL EXAMINE AND 29 00:01:05,239 --> 00:01:07,207 HEAR ABOUT RESEARCH HAPPENING 30 00:01:07,207 --> 00:01:09,376 GLOBALLY IN SICKLE CELL DISEASE, 31 00:01:09,376 --> 00:01:11,478 SPECIFICALLY INDIA, AFRICA AND 32 00:01:11,478 --> 00:01:11,812 BRAZIL. 33 00:01:11,812 --> 00:01:13,447 WE'LL ALSO HEAR PRESENTATIONS 34 00:01:13,447 --> 00:01:15,182 THAT INCLUDE GENOMICS, PUBLIC 35 00:01:15,182 --> 00:01:16,717 HEALTH, AND CLINICAL DATA 36 00:01:16,717 --> 00:01:19,453 RESOURCES TO UNDERSTAND OUTCOMES 37 00:01:19,453 --> 00:01:20,420 IN SICKLE CELL DISEASE, 38 00:01:20,420 --> 00:01:21,855 HIGHLIGHTING THE IMPORTANCE OF 39 00:01:21,855 --> 00:01:23,824 DATA-DRIVEN APPROACHES AND 40 00:01:23,824 --> 00:01:25,159 ENHANCING PATIENT CARE. 41 00:01:25,159 --> 00:01:26,660 ON THE LAST AND THIRD DAY OF THE 42 00:01:26,660 --> 00:01:28,729 WORKSHOP, WE WILL EXPLORE TOPICS 43 00:01:28,729 --> 00:01:29,930 THAT INCLUDE SICKLE CELL DISEASE 44 00:01:29,930 --> 00:01:31,598 PAIN MANAGEMENT, WOMEN'S HEALTH 45 00:01:31,598 --> 00:01:33,534 IN SICKLE CELL DISEASE, AND 46 00:01:33,534 --> 00:01:34,535 EMERGING DISEASE MODIFYING 47 00:01:34,535 --> 00:01:35,402 THERAPIES. 48 00:01:35,402 --> 00:01:37,704 WE WILL ALSO DISCUSS THE ROLE OF 49 00:01:37,704 --> 00:01:40,440 RESEARCH COLLABORATIVES AND 50 00:01:40,440 --> 00:01:42,309 ALLIANCE -- NATIONAL ALLY ANSES 51 00:01:42,309 --> 00:01:43,811 IN ADVANCING SICKLE CELL DISEASE 52 00:01:43,811 --> 00:01:44,378 CARE AND TREATMENT. 53 00:01:44,378 --> 00:01:45,913 SO I HOPE THE MEETING HELPS 54 00:01:45,913 --> 00:01:48,115 FOSTER COLLABORATION AND 55 00:01:48,115 --> 00:01:49,316 ADVANCES OUR SCIENTIFIC 56 00:01:49,316 --> 00:01:49,983 DISCOVERIES IN SICKLE CELL 57 00:01:49,983 --> 00:01:51,518 DISEASE AS WE WORK TO IMPROVE 58 00:01:51,518 --> 00:01:52,986 THE LIVES OF THOSE LIVING WITH 59 00:01:52,986 --> 00:01:54,555 SICKLE CELL DISEASE. 60 00:01:54,555 --> 00:01:55,889 SO THANK YOU ALL FOR JOINING US 61 00:01:55,889 --> 00:02:02,629 AND I'LL TURN THIS OVER TO 62 00:02:02,629 --> 00:02:08,268 DR. QASBA. 63 00:02:08,268 --> 00:02:10,337 >> THANK YOU, JULIE, AND GOOD 64 00:02:10,337 --> 00:02:12,606 MORNING AGAIN TO EVERYBODY, AND 65 00:02:12,606 --> 00:02:17,277 WELCOME TO OUR 2024 MEETING. 66 00:02:17,277 --> 00:02:22,216 SO BEFORE I INTRODUCE OUR FIRST 67 00:02:22,216 --> 00:02:24,284 SYMPOSIUM TO GET STARTED ON, I 68 00:02:24,284 --> 00:02:27,888 JUST HAVE SOME MINOR LOGISTICS 69 00:02:27,888 --> 00:02:30,190 THAT YOU MAY OR MAY NOT BE 70 00:02:30,190 --> 00:02:30,624 AWARE. 71 00:02:30,624 --> 00:02:36,763 IN TERMS OF THE CAFETERIA, THE 72 00:02:36,763 --> 00:02:38,298 NATCHER CAFETERIA IS CLOSED ON 73 00:02:38,298 --> 00:02:39,633 MONDAYS, BUT IT WILL BE OPEN 74 00:02:39,633 --> 00:02:42,502 TUESDAY AND WEDNESDAY. 75 00:02:42,502 --> 00:02:44,304 SO FOR FOLKS WHO HAVE ORDERED 76 00:02:44,304 --> 00:02:46,039 THEIR FOOD AND ALL THAT STUFF 77 00:02:46,039 --> 00:02:48,709 WITH THE CONTRACTS PEOPLE, YOU 78 00:02:48,709 --> 00:02:51,645 CAN COLLECT THAT AT THE TIME OF 79 00:02:51,645 --> 00:02:53,180 LUNCH. 80 00:02:53,180 --> 00:02:57,084 AND EVERYBODY ELSE IS FAMILIAR 81 00:02:57,084 --> 00:02:59,519 WITH THE RESTROOMS ON YOUR RIGHT 82 00:02:59,519 --> 00:03:02,489 AND LEFT, ET CETERA. 83 00:03:02,489 --> 00:03:07,261 AND I WOULD URGE ALL THE 84 00:03:07,261 --> 00:03:09,563 SPEAKERS TO PLEASE STAY ON TIME. 85 00:03:09,563 --> 00:03:13,400 WE HAVE A VERY ASTUTE TIMEKEEPER 86 00:03:13,400 --> 00:03:15,035 HERE, AND WE'LL HOPEFULLY KEEP 87 00:03:15,035 --> 00:03:17,771 YOU ON TIME. 88 00:03:17,771 --> 00:03:19,072 AND OTHER THAN THAT, I REALLY 89 00:03:19,072 --> 00:03:21,275 DON'T HAVE MUCH TO SAY, AGAIN, 90 00:03:21,275 --> 00:03:23,377 WELCOME AGAIN TO THIS WONDERFUL 91 00:03:23,377 --> 00:03:24,011 MEETING. 92 00:03:24,011 --> 00:03:25,646 AND JULIE HAS ALREADY SUMMARIZED 93 00:03:25,646 --> 00:03:26,847 THE DIFFERENT AREAS THAT WE'LL 94 00:03:26,847 --> 00:03:33,820 BE TALKING ABOUT. 95 00:03:33,820 --> 00:03:36,290 SO WITHOUT ANY FURTHER DELAYS, I 96 00:03:36,290 --> 00:03:40,360 THINK I'LL GET STARTED. 97 00:03:40,360 --> 00:03:44,164 AND WELCOME THE CO-CHAIRS, 98 00:03:44,164 --> 00:03:45,399 DR. LAKSHMANAN KRISHNAMURTI AND 99 00:03:45,399 --> 00:03:47,768 BETH STENGER FOR GETTING STARTED 100 00:03:47,768 --> 00:03:50,003 WITH THE SYMPOSIUM 1, WHICH IS 101 00:03:50,003 --> 00:03:52,105 UPDATES ON GENE AND CELL THERAPY 102 00:03:52,105 --> 00:03:53,774 AND OTHER THERAPEUTICS FOR 103 00:03:53,774 --> 00:04:03,216 SICKLE CELL DISEASE. 104 00:04:03,216 --> 00:04:13,560 KRISH, DR. STENGER? 105 00:04:22,869 --> 00:04:24,004 >> GOOD MORNING. 106 00:04:24,004 --> 00:04:31,778 WELCOME TO THE KICKOFF SESSION. 107 00:04:31,778 --> 00:04:34,514 [SPEAKER NOT ON MIC] 108 00:04:34,514 --> 00:04:36,016 >> THIS WOULD WORK A LOT BETTER 109 00:04:36,016 --> 00:04:38,552 IF THE MIC WAS ON. 110 00:04:38,552 --> 00:04:41,154 SO IT'S MY PLEASURE TO INTRODUCE 111 00:04:41,154 --> 00:04:43,156 MYCO-CHAIR, DR. BETH STENGER. 112 00:04:43,156 --> 00:04:46,660 DR. STENGER, TAKE IT AWAY. 113 00:04:46,660 --> 00:04:56,703 >> I THINK WE HAVE SOME SLIDES. 114 00:04:56,703 --> 00:05:01,541 SO OUR SESSION IS ENTITLED 115 00:05:01,541 --> 00:05:02,676 HEMATOPOIETIC CELL 116 00:05:02,676 --> 00:05:04,044 TRANSPLANTATION, AND WE WILL 117 00:05:04,044 --> 00:05:05,379 BE -- IF YOU CAN GO TO THE NEXT 118 00:05:05,379 --> 00:05:08,548 SLIDE, WE'LL BE -- HAVE EIGHT 119 00:05:08,548 --> 00:05:09,850 SPEAKERS IN OUR SESSION WHO WILL 120 00:05:09,850 --> 00:05:13,820 BE PRESENTING DATA FROM 121 00:05:13,820 --> 00:05:16,523 PUBLICATIONS FROM THIS PAST 122 00:05:16,523 --> 00:05:18,392 YEAR, AND EACH SPEAKER WILL HAVE 123 00:05:18,392 --> 00:05:19,059 ABOUT 10 MINUTES FOR 124 00:05:19,059 --> 00:05:19,793 PRESENTATION AND QUESTIONS AND 125 00:05:19,793 --> 00:05:23,096 HOPEFULLY WE CAN STAY ON 126 00:05:23,096 --> 00:05:24,264 SCHEDULE. 127 00:05:24,264 --> 00:05:26,066 JUST TO NOTE, THE ORDER OF 128 00:05:26,066 --> 00:05:27,334 SPEAKERS LISTED ON THIS SLIDE IS 129 00:05:27,334 --> 00:05:28,335 DIFFERENT THAN WHAT IS IN THE 130 00:05:28,335 --> 00:05:30,270 PROGRAM NOTES AND I'LL PUT THAT 131 00:05:30,270 --> 00:05:34,674 IN THE CHAT FOR FOLKS WHO ARE 132 00:05:34,674 --> 00:05:36,209 ONLINE AS WELL AND PLEASE DO PUT 133 00:05:36,209 --> 00:05:37,310 QUESTIONS IN THE CHAT. 134 00:05:37,310 --> 00:05:38,812 WE'LL BE MONITORING THOSE AND 135 00:05:38,812 --> 00:05:43,450 CAN READ THEM ALOUD FOR THE 136 00:05:43,450 --> 00:05:44,084 AUDIENCE AS WELL. 137 00:05:44,084 --> 00:05:46,720 SO WITH THAT, I'LL TURN OVER TO 138 00:05:46,720 --> 00:05:50,357 DR. KRISH TO INTRODUCE OUR FIRST 139 00:05:50,357 --> 00:05:50,590 SPEAKER. 140 00:05:50,590 --> 00:05:53,026 >> IT QUITE LOVELY THAT WE'RE 141 00:05:53,026 --> 00:05:54,161 STARTING TO THE NOD WITH THE 142 00:05:54,161 --> 00:05:55,595 USUAL OUTCOMES OF TRANSPLANT THE 143 00:05:55,595 --> 00:05:56,763 WAY WE'RE USED TO, BUT ABOUT 144 00:05:56,763 --> 00:05:58,932 SOMETHING THAT'S REALLY 145 00:05:58,932 --> 00:06:00,834 IMPORTANT THAT HAPPENS AFTER 146 00:06:00,834 --> 00:06:01,134 TRANSPLANT. 147 00:06:01,134 --> 00:06:02,803 AND WHAT WE CAN DO ABOUT IT 148 00:06:02,803 --> 00:06:04,671 BEFORE TRANSPLANT. 149 00:06:04,671 --> 00:06:06,306 THIS IS THE WHOLE FERTILITY 150 00:06:06,306 --> 00:06:09,009 QUESTION AND FERTILITY 151 00:06:09,009 --> 00:06:09,676 PRESERVATION. 152 00:06:09,676 --> 00:06:11,878 SO TO START OFF OUR CONVERSATION 153 00:06:11,878 --> 00:06:14,915 TODAY, DR. TAMARA 154 00:06:14,915 --> 00:06:15,782 DIESCH-FURLANETTO FROM THE 155 00:06:15,782 --> 00:06:16,383 UNIVERSITY CHILDREN'S HOSPITAL 156 00:06:16,383 --> 00:06:19,519 IN BASEL, SWITZERLAND WILL BE 157 00:06:19,519 --> 00:06:21,855 TALKING TO US ABOUT 158 00:06:21,855 --> 00:06:22,689 CRYOPRESERVATION OF OVARIAN 159 00:06:22,689 --> 00:06:25,659 TISSUE IN SICKLE CELL PATIENTS 160 00:06:25,659 --> 00:06:27,461 PRIOR TO STEM CELL 161 00:06:27,461 --> 00:06:28,562 TRANSPLANTATION, SAFETY, 162 00:06:28,562 --> 00:06:30,030 FOLLOW-UP AND OUTCOMES OF 163 00:06:30,030 --> 00:06:31,965 OVARIAN TISSUE TRANSPLANTATION. 164 00:06:31,965 --> 00:06:35,035 AND THIS IS A RECORDED 165 00:06:35,035 --> 00:06:36,136 PRESENTATION, AND DR. TAMARA 166 00:06:36,136 --> 00:06:44,010 SAID SHE WILL BE ON. 167 00:06:44,010 --> 00:06:44,778 WELCOME, DR. TAMARA. 168 00:06:44,778 --> 00:06:46,413 >> GOOD MORNING. 169 00:06:46,413 --> 00:06:48,281 FIRST OF ALL, I WANT TO THANK 170 00:06:48,281 --> 00:06:51,551 THE ORGANIZER FOR GIVING ME THE 171 00:06:51,551 --> 00:06:52,752 OPPORTUNITY TO PRESENT OUR 172 00:06:52,752 --> 00:06:54,421 STUDY. 173 00:06:54,421 --> 00:07:01,094 ON BEHALF OF ALL OF US, I WILL 174 00:07:01,094 --> 00:07:03,363 PRESENT OUR STUDY ON 175 00:07:03,363 --> 00:07:05,232 CRYOPRESERVATION OF OVARIAN 176 00:07:05,232 --> 00:07:07,868 TISSUE IN SICKLE CELL PATIENTS 177 00:07:07,868 --> 00:07:09,936 PRIOR TO STEM CELL 178 00:07:09,936 --> 00:07:12,105 TRANSPLANTATION. 179 00:07:12,105 --> 00:07:14,441 SAFETY, FOLLOW-UP AND OUTCOMES 180 00:07:14,441 --> 00:07:17,711 OF OVARIAN TISSUE 181 00:07:17,711 --> 00:07:20,647 TRANSPLANTATIONS. 182 00:07:20,647 --> 00:07:26,820 I HAVE NOTHING TO DISCLOSE. 183 00:07:26,820 --> 00:07:30,590 AS YOU KNOW, STEM CELL 184 00:07:30,590 --> 00:07:32,159 TRANSPLANTATION IS A CURATIVE 185 00:07:32,159 --> 00:07:33,760 OPTION FOR PATIENTS WITH SICKLE 186 00:07:33,760 --> 00:07:35,896 CELL DISEASE. 187 00:07:35,896 --> 00:07:37,831 THE ADVANTAGE IS A VERY GOOD 188 00:07:37,831 --> 00:07:44,271 OVERALL SURVIVAL OF ABOUT 98%, 189 00:07:44,271 --> 00:07:45,739 ESPECIALLY IN MATCHED SIBLING 190 00:07:45,739 --> 00:07:47,774 DONOR. 191 00:07:47,774 --> 00:07:53,346 THE DISADVANTAGE IS THAT AFTER 192 00:07:53,346 --> 00:07:55,115 ABLATIVE CONDITIONING REGIMEN, 193 00:07:55,115 --> 00:07:57,184 MOST OF THE PATIENTS HAVE A 194 00:07:57,184 --> 00:08:00,020 PREMATURE OVARIAN INSUFFICIENCY, 195 00:08:00,020 --> 00:08:04,858 AND PREGNANCY RATE IS REALLY 196 00:08:04,858 --> 00:08:07,027 LOW, ABOUT 2%. 197 00:08:07,027 --> 00:08:10,430 SO FERTILITY PRESERVATION IS A 198 00:08:10,430 --> 00:08:13,500 MAJOR ISSUE IN SICKLE CELL 199 00:08:13,500 --> 00:08:19,039 DISEASE CARE. 200 00:08:19,039 --> 00:08:20,473 WHICH OPTIONS CONCERNING 201 00:08:20,473 --> 00:08:22,008 FERTILITY PRESERVATION CAN BE 202 00:08:22,008 --> 00:08:22,642 OFFERED? 203 00:08:22,642 --> 00:08:28,515 ONE, WE HAVE ALL -- 204 00:08:28,515 --> 00:08:29,649 CRYOPRESERVATION, AND ON THE 205 00:08:29,649 --> 00:08:31,851 OTHER HAND OVARIAN TISSUE 206 00:08:31,851 --> 00:08:36,590 CRYOPRESERVATION. 207 00:08:36,590 --> 00:08:39,926 -- CRYOPRESERVATION CAN BE 208 00:08:39,926 --> 00:08:41,394 PERFORMED IN POST PUBERTAL 209 00:08:41,394 --> 00:08:41,895 PATIENTS. 210 00:08:41,895 --> 00:08:45,532 THEY NEED HORMONAL STIMULATION 211 00:08:45,532 --> 00:08:50,470 OF ABOUT 12 DAYS, AND THE OOCYTE 212 00:08:50,470 --> 00:08:52,105 WILL BE EXTRACTED BY VAGINAL 213 00:08:52,105 --> 00:08:56,476 ACCESS. 214 00:08:56,476 --> 00:08:59,846 OVARIAN STIMULATION HAS MANY 215 00:08:59,846 --> 00:09:04,451 RISKS, SUCH AS THROMBOGENIC 216 00:09:04,451 --> 00:09:08,054 INDUCED VASO-OCCLUSIVE CRISIS. 217 00:09:08,054 --> 00:09:10,123 THE FIRST CASE OF OOCYTE 218 00:09:10,123 --> 00:09:11,925 CRYOPRESERVATION WAS REPORTED IN 219 00:09:11,925 --> 00:09:14,094 2012 BY DOVEY. 220 00:09:14,094 --> 00:09:16,896 THE PATIENTS RECEIVED A MINIMAL 221 00:09:16,896 --> 00:09:21,601 STIMULATION PROTOCOL, THROMBOSIS 222 00:09:21,601 --> 00:09:23,703 PROPHYLAXIS AND INTRAVENOUS 223 00:09:23,703 --> 00:09:25,672 HYPERHYDRATION. 224 00:09:25,672 --> 00:09:27,641 WHEN WE LOOK TO THE LITERATURE, 225 00:09:27,641 --> 00:09:31,544 SO WE SEE THAT THE MAJORITY OF 226 00:09:31,544 --> 00:09:34,681 THE PATIENTS HAD AN ACUTE PAIN 227 00:09:34,681 --> 00:09:36,716 CRISIS AND THE NEEDED SUPPORTIVE 228 00:09:36,716 --> 00:09:40,987 CARE, SUCH AS INTRAVENOUS 229 00:09:40,987 --> 00:09:44,691 HYDRATION, BLOOD EXCHANGE, OR 230 00:09:44,691 --> 00:09:50,363 HOSPITALIZATION ON ICU. 231 00:09:50,363 --> 00:09:53,199 WHAT WE ALSO SEE IS THAT THE 232 00:09:53,199 --> 00:09:55,935 OOCYTE YIELD FOR PATIENTS WITH 233 00:09:55,935 --> 00:09:57,404 SICKLE CELL DISEASE COMPARED TO 234 00:09:57,404 --> 00:10:00,573 NORMAL POPULATION IS SUBOPTIMAL. 235 00:10:00,573 --> 00:10:04,644 UNTIL NOW, FEW CASES OF EMBRYO 236 00:10:04,644 --> 00:10:06,846 CRYOPRESERVATION HAVE BEEN 237 00:10:06,846 --> 00:10:09,115 REPORTED, AND WE HAVE NO REPORTS 238 00:10:09,115 --> 00:10:13,687 ON THE USE OF THE OOCYTES UNTIL 239 00:10:13,687 --> 00:10:15,455 NOW. 240 00:10:15,455 --> 00:10:16,956 OVARIAN TISSUE CRYOPRESERVATION 241 00:10:16,956 --> 00:10:21,461 CAN BE APPLIED IN PRE AND POST 242 00:10:21,461 --> 00:10:25,165 PUBERTAL PATIENTS. 243 00:10:25,165 --> 00:10:30,103 ONE OVER VEE WI OVARY WILL BE RD 244 00:10:30,103 --> 00:10:32,405 COMPLETELY SO WE HAVE ONE 245 00:10:32,405 --> 00:10:34,474 IMMATURE OOCYTE AND IT WILL BE 246 00:10:34,474 --> 00:10:36,343 CAPTURED IN SMALL SECTIONS, 247 00:10:36,343 --> 00:10:38,178 SO-CALLED FRAGMENTS, WHICH WILL 248 00:10:38,178 --> 00:10:41,715 BE CRYOPRESERVED. 249 00:10:41,715 --> 00:10:43,249 IT'S POSSIBLE TO COMBINE IT WITH 250 00:10:43,249 --> 00:10:46,753 OTHER SURGICAL PROCEDURES. 251 00:10:46,753 --> 00:10:49,823 AND AFTER YOU CAN PERFORM 252 00:10:49,823 --> 00:10:54,694 OVARIAN TISSUE TRANSPLANTATION. 253 00:10:54,694 --> 00:10:58,965 SO IN OUR STUDY, WE INCLUDED 75 254 00:10:58,965 --> 00:11:01,468 GIRLS AND WOMEN WITH SICKLE CELL 255 00:11:01,468 --> 00:11:04,104 DISEASE. 256 00:11:04,104 --> 00:11:05,972 ALL HAD AN INDICATION FOR STEM 257 00:11:05,972 --> 00:11:08,908 CELL TRANSPLANTATION. 258 00:11:08,908 --> 00:11:11,444 THEY HAD CEREBRAL VASCULOPATHY 259 00:11:11,444 --> 00:11:13,213 OR RECURRENT VASO-OCCLUSIVE 260 00:11:13,213 --> 00:11:18,451 CRISIS DESPITE HYDROXYYOU'RE YA 261 00:11:18,451 --> 00:11:18,885 TREATMENT. 262 00:11:18,885 --> 00:11:20,286 OVARIAN TISSUE CRYOPRESERVATION 263 00:11:20,286 --> 00:11:23,156 WAS PERFORMED BETWEEN APRIL 1998 264 00:11:23,156 --> 00:11:28,528 AND DECEMBER 2018, PRIOR TO STEM 265 00:11:28,528 --> 00:11:31,030 CELL TRANSPLANTATION. 266 00:11:31,030 --> 00:11:35,168 ALL PATIENTS RECEIVED A BLOOD 267 00:11:35,168 --> 00:11:37,570 EXCHANGE BEFORE OVARIAN TISSUE 268 00:11:37,570 --> 00:11:41,975 CRYOPRESERVATION TO ACHIEVE A 269 00:11:41,975 --> 00:11:44,744 HBS LEVEL BELOW 30%. 270 00:11:44,744 --> 00:11:48,381 HERE YOU CAN SEE PATIENTS' 271 00:11:48,381 --> 00:11:50,150 CHARACTERISTICS. 272 00:11:50,150 --> 00:11:51,584 MEDIAN AGE AT TIME POINT OF 273 00:11:51,584 --> 00:11:56,055 OVARIAN TISSUE CRYOPRESERVATION 274 00:11:56,055 --> 00:11:59,058 WAS 9.6 AND MEDIAN TIME BETWEEN 275 00:11:59,058 --> 00:12:01,227 OVARIAN TISSUE CRYOPRESERVATION 276 00:12:01,227 --> 00:12:06,065 AND STEM CELL TRANSPLANTATION 277 00:12:06,065 --> 00:12:09,302 WAS EIGHT MONTHS. 278 00:12:09,302 --> 00:12:13,039 AT FOLLOW-UP THE MEDIAN AGE WAS 279 00:12:13,039 --> 00:12:17,177 9.3 YEARS. 280 00:12:17,177 --> 00:12:23,283 FROM THE 75 PATIENTS, 56 OF THEM 281 00:12:23,283 --> 00:12:25,285 WERE PRE-PUBERTAL. 282 00:12:25,285 --> 00:12:32,492 ALL HAD A -- OWE BLAITIVE 283 00:12:32,492 --> 00:12:33,026 CONDITIONING REGIMEN. 284 00:12:33,026 --> 00:12:34,994 ONE RECEIVED OVARIAN TISSUE 285 00:12:34,994 --> 00:12:36,329 TRANSPLANTATION TO INDUCE 286 00:12:36,329 --> 00:12:38,598 PUBERTY. 287 00:12:38,598 --> 00:12:41,000 AT LAST FOLLOW-UP, WE HAD 288 00:12:41,000 --> 00:12:48,341 RECORDS FROM 49 PATIENTS. 289 00:12:48,341 --> 00:12:51,211 96% OF THEM HAD A PRIMARY 290 00:12:51,211 --> 00:12:55,215 OVARIAN INSUFFICIENCY. 291 00:12:55,215 --> 00:13:00,286 FROM THE 75 PATIENTS, 19 WERE 292 00:13:00,286 --> 00:13:06,826 POST PUBERTAL. 293 00:13:06,826 --> 00:13:08,261 TWO -- RELATED TO TRANSPLANT 294 00:13:08,261 --> 00:13:09,462 MORTALITY AND TWO WERE LOST 295 00:13:09,462 --> 00:13:12,298 DAWRNG FOLLOW-U -- 296 00:13:12,298 --> 00:13:13,266 DURING FOLLOW-UP. 297 00:13:13,266 --> 00:13:15,902 SO 15 OF THEM, SO ALL OF THEM 298 00:13:15,902 --> 00:13:19,005 HAD A PRIMARY OVARIAN 299 00:13:19,005 --> 00:13:20,173 INSUFFICIENCY AFTER STEM CELL 300 00:13:20,173 --> 00:13:25,745 TRANSPLANTATION. 301 00:13:25,745 --> 00:13:28,147 FOUR OF THEM HAD OVARIAN TISSUE 302 00:13:28,147 --> 00:13:29,249 TRANSPLANTATION TO RESTORE 303 00:13:29,249 --> 00:13:30,783 FERTILITY. 304 00:13:30,783 --> 00:13:35,922 HERE YOU CAN SEE THE PATIENTS' 305 00:13:35,922 --> 00:13:38,224 CHARACTERISTICS OF PATIENTS WHO 306 00:13:38,224 --> 00:13:40,727 UNDERWENT OVARIAN TISSUE 307 00:13:40,727 --> 00:13:42,595 TRANSPLANTATION. 308 00:13:42,595 --> 00:13:46,199 PATIENT 5 IS THE PREPUBERTAL 309 00:13:46,199 --> 00:13:50,036 PATIENT WHO HAD OVARIAN TISSUE 310 00:13:50,036 --> 00:13:52,272 TRANSPLANTATION TO INDUCE 311 00:13:52,272 --> 00:13:56,376 PUBERTY, AND PATIENT 1 TO 4 WERE 312 00:13:56,376 --> 00:13:57,677 POST PUBERTAL. 313 00:13:57,677 --> 00:13:59,879 ALL HAD THEIR RECOVERY OF 314 00:13:59,879 --> 00:14:05,118 OVARIAN FUNCTION. 315 00:14:05,118 --> 00:14:07,353 PATIENT 4 CAME FOR THE FIRST 316 00:14:07,353 --> 00:14:10,456 TIME NINE MONTHS AFTER STEM CELL 317 00:14:10,456 --> 00:14:11,958 TRANSPLANTATION, AND THE 318 00:14:11,958 --> 00:14:13,860 EXAMINATION REVEALED THAT SHE 319 00:14:13,860 --> 00:14:16,763 WAS PREGNANT. 320 00:14:16,763 --> 00:14:18,765 SHE BORNE A HEALTHY CHILD. 321 00:14:18,765 --> 00:14:20,633 MEDIAN TIME BETWEEN OVARIAN 322 00:14:20,633 --> 00:14:23,603 TISSUE TRANSPLANTATION AND 323 00:14:23,603 --> 00:14:28,074 OVARIAN FUNCTION RECOVERY WAS 324 00:14:28,074 --> 00:14:28,641 4 TO 6 MONTHS. 325 00:14:28,641 --> 00:14:32,345 NO SEVERE COMPLICATIONS WERE 326 00:14:32,345 --> 00:14:35,848 REPORTED. 327 00:14:35,848 --> 00:14:37,917 SO IN CONCLUSION, WE CAN SAY 328 00:14:37,917 --> 00:14:40,553 OVARIAN TISSUE CRYOPRESERVATION 329 00:14:40,553 --> 00:14:44,958 CAN BE PROPOSED INDEPENDENTLY OF 330 00:14:44,958 --> 00:14:47,794 THE AGE FOR PRE AND POST 331 00:14:47,794 --> 00:14:48,995 PUBERTAL UNDER THE AGE OF 35 332 00:14:48,995 --> 00:14:51,598 YEARS. 333 00:14:51,598 --> 00:14:52,765 IT'S SAFE. 334 00:14:52,765 --> 00:14:58,371 NO MAJOR COMPLICATION WERE 335 00:14:58,371 --> 00:15:00,239 REPORTED, IMPORTANT TO PERFORM 336 00:15:00,239 --> 00:15:02,976 BLOOD EXCHANGE BEFORE OVARIAN 337 00:15:02,976 --> 00:15:03,876 TISSUE CRYOPRESERVATION, AND 338 00:15:03,876 --> 00:15:06,312 OVARIAN TISSUE TRANSPLANTATION 339 00:15:06,312 --> 00:15:09,349 IS AN OPTION TO RESTORE OVARIAN 340 00:15:09,349 --> 00:15:13,820 FUNCTION AND FERTILITY. 341 00:15:13,820 --> 00:15:16,589 I WANT TO THANK ALL PATIENTS AND 342 00:15:16,589 --> 00:15:19,425 THEIR FAMILIES FOR THEIR 343 00:15:19,425 --> 00:15:20,426 PARTICIPATION AND YOU FOR YOUR 344 00:15:20,426 --> 00:15:21,628 ATTENTION. 345 00:15:21,628 --> 00:15:29,469 THANK YOU VERY MUCH. 346 00:15:29,469 --> 00:15:29,736 [APPLAUSE] 347 00:15:29,736 --> 00:15:30,069 >> THANK YOU. 348 00:15:30,069 --> 00:15:31,137 THAT WAS A WONDERFUL 349 00:15:31,137 --> 00:15:31,471 PRESENTATION. 350 00:15:31,471 --> 00:15:33,840 THANK YOU, DR. TAMARA. 351 00:15:33,840 --> 00:15:37,577 QUESTIONS FROM THE AUDIENCE? 352 00:15:37,577 --> 00:15:38,211 FOR 353 00:15:38,211 --> 00:15:43,916 DR. TAMARA? 354 00:15:43,916 --> 00:15:45,318 I'D LIKE TO START OFF IF I MAY, 355 00:15:45,318 --> 00:15:47,320 SO ONLY A SMALL MINORITY OF THE 356 00:15:47,320 --> 00:15:50,356 PATIENTS WHO HAD OVARIAN TISSUE 357 00:15:50,356 --> 00:15:52,592 CRYOPRESERVATION ACTUALLY WENT 358 00:15:52,592 --> 00:15:54,093 FORWARD WITH TRANSPLANTING THE 359 00:15:54,093 --> 00:15:55,495 TISSUE. 360 00:15:55,495 --> 00:15:56,596 COULD YOU TALK A LITTLE BIT 361 00:15:56,596 --> 00:16:00,667 ABOUT SOME OF THE REASONS WHY? 362 00:16:00,667 --> 00:16:03,469 >> YES, THANK YOU. 363 00:16:03,469 --> 00:16:05,004 I HAVE JUST A PROBLEM WITH MY 364 00:16:05,004 --> 00:16:05,338 CAMERA. 365 00:16:05,338 --> 00:16:08,074 SO MOST OF THEM DIDN'T REACH THE 366 00:16:08,074 --> 00:16:10,476 AGE TO THINK ABOUT THEIR OWN 367 00:16:10,476 --> 00:16:12,111 CHILD. 368 00:16:12,111 --> 00:16:13,546 THAT'S WHY IT WAS NOT USED 369 00:16:13,546 --> 00:16:15,748 OVARIAN TISSUE TRANSPLANTATION 370 00:16:15,748 --> 00:16:17,817 IN THESE PATIENTS. 371 00:16:17,817 --> 00:16:19,786 I THINK IN FIVE TO 10 YEARS, WE 372 00:16:19,786 --> 00:16:22,822 WILL HAVE MORE DETAILS, MORE 373 00:16:22,822 --> 00:16:23,723 INFORMATION. 374 00:16:23,723 --> 00:16:26,225 AND MORE PATIENTS COMING BACK TO 375 00:16:26,225 --> 00:16:27,660 ASKING THEIR TISSUE. 376 00:16:27,660 --> 00:16:30,396 >> SO IN EUROPE, COST MIGHT NOT 377 00:16:30,396 --> 00:16:32,432 HAVE BEEN A CONSIDERATION? 378 00:16:32,432 --> 00:16:35,435 >> WELL, IN FRANCE, IT'S COVERED 379 00:16:35,435 --> 00:16:38,071 BY HEALTH INSURANCE. 380 00:16:38,071 --> 00:16:40,106 IN SWITZERLAND, IT'S COVERED IN 381 00:16:40,106 --> 00:16:42,608 POST PUBERTAL PATIENTS. 382 00:16:42,608 --> 00:16:51,617 IN PREPREU PREPUBERTAL IT'S STN 383 00:16:51,617 --> 00:16:53,219 AS EXPERIMENTATION. 384 00:16:53,219 --> 00:16:54,353 >> OTHER QUESTIONS FOR 385 00:16:54,353 --> 00:17:03,096 DR. TAMARA? 386 00:17:03,096 --> 00:17:05,698 >> WE HAVE A QUESTION HERE ON 387 00:17:05,698 --> 00:17:12,105 THE EFFECT OF HYDROXYUREA. 388 00:17:12,105 --> 00:17:15,608 "I MISSED THE EFFECT OF 389 00:17:15,608 --> 00:17:15,942 HYDROXYUREA." 390 00:17:15,942 --> 00:17:17,343 >> SO IN THIS STUDY, WE JUST 391 00:17:17,343 --> 00:17:19,979 LOOKED TO SAFETY FOLLOW-UP AND 392 00:17:19,979 --> 00:17:21,547 OUTCOME OF OVARIAN TISSUE 393 00:17:21,547 --> 00:17:23,816 TRANSPLANTATION, BUT WE JUST 394 00:17:23,816 --> 00:17:27,587 PUBLISHED A PUBLICATION ON THE 395 00:17:27,587 --> 00:17:32,024 IMPACT OF HYDROXYUREA ON OVARIAN 396 00:17:32,024 --> 00:17:33,559 RESERVE AND WE DIDN'T SEE A 397 00:17:33,559 --> 00:17:34,861 SIGNIFICANT ALTERATION OF 398 00:17:34,861 --> 00:17:37,830 OVARIAN RESERVE IN PATIENTS 399 00:17:37,830 --> 00:17:38,698 UNDER HYDROXYUREA TREATMENT 400 00:17:38,698 --> 00:17:42,735 COMPARED TO THOSE WITHOUT HIGH 401 00:17:42,735 --> 00:17:43,035 HYDROXYUREA. 402 00:17:43,035 --> 00:17:45,371 >> WE HAVE ANOTHER EXCELLENT 403 00:17:45,371 --> 00:17:48,975 QUESTION ABOUT THE RELATIVE 404 00:17:48,975 --> 00:17:51,511 COMPLICATIONS OF -- IN SICKLE 405 00:17:51,511 --> 00:17:52,478 CELL DISEASE VERSUS OTHER 406 00:17:52,478 --> 00:17:53,880 PATIENTS IN TERMS OF THE 407 00:17:53,880 --> 00:17:57,283 PROCEDURES FOR OVARIAN 408 00:17:57,283 --> 00:17:58,484 CRYOPRESERVATION OR STEM CELL -- 409 00:17:58,484 --> 00:18:00,353 OR COLLECTION OF OOCYTES. 410 00:18:00,353 --> 00:18:05,491 >> WELL, THE INCIDENCE OF 411 00:18:05,491 --> 00:18:06,325 HYPERSTIMULATION SYNDROME IS 412 00:18:06,325 --> 00:18:09,262 HIGHER IN PATIENTS WITH SICKLE 413 00:18:09,262 --> 00:18:12,732 CELL DISEASE COMPARED TO NORMAL 414 00:18:12,732 --> 00:18:14,567 POPULATION, AND AS I SHOWED THE 415 00:18:14,567 --> 00:18:17,003 OOCYTE YIELD IS LOWER IN 416 00:18:17,003 --> 00:18:18,070 PATIENTS WITH SICKLE CELL 417 00:18:18,070 --> 00:18:20,807 DISEASE COMPARED TO NORMAL 418 00:18:20,807 --> 00:18:22,241 POPULATION. 419 00:18:22,241 --> 00:18:22,909 IT'S JUST IMPORTANT THAT THEY 420 00:18:22,909 --> 00:18:23,309 KNOW IT. 421 00:18:23,309 --> 00:18:24,977 >> EXCELLENT. 422 00:18:24,977 --> 00:18:26,612 SO TO PREVENT HYPERSTIMULATION 423 00:18:26,612 --> 00:18:28,447 SYNDROME, DID YOU DO HYDRATION, 424 00:18:28,447 --> 00:18:30,650 DID YOU DO ANTI-COAGULATION? 425 00:18:30,650 --> 00:18:31,951 CAN YOU EDUCATE US -- 426 00:18:31,951 --> 00:18:33,719 >> YES, EXACTLY. 427 00:18:33,719 --> 00:18:38,658 SO PATIENTS -- AS YOU SAW BY 428 00:18:38,658 --> 00:18:41,494 DOVEY AND ALL, WE PROPOSED 429 00:18:41,494 --> 00:18:46,732 THROMBOSIS PROPHYLAXIS, WE 430 00:18:46,732 --> 00:18:47,400 MAKE -- HYDRATION. 431 00:18:47,400 --> 00:18:47,834 IT'S IMPORTANT. 432 00:18:47,834 --> 00:18:50,002 AND YOU NEED A LOWER DOSE FOR 433 00:18:50,002 --> 00:18:52,972 HORMONAL STIMULATION. 434 00:18:52,972 --> 00:18:53,840 >> THANK YOU. 435 00:18:53,840 --> 00:18:56,142 PLEASE GIVE IT UP FOR DR. TAMARA 436 00:18:56,142 --> 00:18:56,576 DIESCH-FURLANETTO. 437 00:18:56,576 --> 00:18:57,043 THANK YOU VERY MUCH. 438 00:18:57,043 --> 00:18:58,110 [APPLAUSE] 439 00:18:58,110 --> 00:19:02,281 >> THANK YOU. 440 00:19:02,281 --> 00:19:04,217 >> SO WE'LL MOVE TO OUR NEXT 441 00:19:04,217 --> 00:19:10,590 SPEAKER, DR. KISS T CHRISTINA PS 442 00:19:10,590 --> 00:19:18,764 FROM VIENNA, AUSTRIA, LOOKING AT 443 00:19:18,764 --> 00:19:20,533 CONDITIONING BEFORE ALLOGENEIC 444 00:19:20,533 --> 00:19:22,368 TRANSPLANT FROM MATCH SIBLING 445 00:19:22,368 --> 00:19:23,502 DONORS IN PEDIATRIC PATIENTS 446 00:19:23,502 --> 00:19:27,974 WITH SICKLE CELL DISEASE. 447 00:19:27,974 --> 00:19:28,841 >> THANK YOU SO MUCH. 448 00:19:28,841 --> 00:19:31,677 IT IS WONDERFUL TO PARTICIPATE 449 00:19:31,677 --> 00:19:35,314 IN THIS GREAT WORKSHOP. 450 00:19:35,314 --> 00:19:39,018 I WANT TO HIGHLIGHT AND COMPARE 451 00:19:39,018 --> 00:19:40,953 TWO VERY POPULAR CONDITIONING 452 00:19:40,953 --> 00:19:44,257 REGIMEN HERE YOU SEE MY 453 00:19:44,257 --> 00:19:48,060 DISCLOSURES. 454 00:19:48,060 --> 00:19:49,362 BECAUSE AS WE LEARNED OVER THE 455 00:19:49,362 --> 00:19:52,431 YEARS, WE HAVE DEMONSTRATED AND 456 00:19:52,431 --> 00:19:54,834 LEARNED THAT MYELOABLATIVE 457 00:19:54,834 --> 00:19:57,670 CONDITIONING REGIMEN BEFORE 458 00:19:57,670 --> 00:19:58,337 ALLOGENIC STEM CELL 459 00:19:58,337 --> 00:20:00,172 TRANSPLANTATION PERHAPS IS MORE 460 00:20:00,172 --> 00:20:03,676 USEFUL THAN IN NON-MYELOABLATIVE 461 00:20:03,676 --> 00:20:06,746 CONDITIONING, ESPECIALLY IN 462 00:20:06,746 --> 00:20:14,086 PATIENTS WHO ARE -- 463 00:20:14,086 --> 00:20:14,420 PRETRANSFUSED. 464 00:20:14,420 --> 00:20:16,255 BECAUSE IF WE DESTROY OR 465 00:20:16,255 --> 00:20:17,523 ERADICATE PATIENTS' BONE MARROW, 466 00:20:17,523 --> 00:20:20,359 WE HAVE AN ELIMINATION OF THE 467 00:20:20,359 --> 00:20:22,228 DEFECTIVE RED BLOOD CELL. 468 00:20:22,228 --> 00:20:26,832 IT IS AN OLD HISTORY THAT WE 469 00:20:26,832 --> 00:20:28,134 PERHAPS NEED SPACE FOR THE DONOR 470 00:20:28,134 --> 00:20:31,504 STEM CELLS. 471 00:20:31,504 --> 00:20:33,272 AND WE ALSO HAVE SHOWN THAT 472 00:20:33,272 --> 00:20:35,775 ENGRAFTING OCCURS EARLIER AND 473 00:20:35,775 --> 00:20:41,414 BETTER IF WE HAVE EMPTY BONE 474 00:20:41,414 --> 00:20:42,348 MARROW IN THE PATIENT. 475 00:20:42,348 --> 00:20:44,283 OF COURSE WE HAVE TO SUPPRESS 476 00:20:44,283 --> 00:20:48,354 THE IMMUNE SYSTEM TO PREVENT 477 00:20:48,354 --> 00:20:51,023 REJECTION, AND ALSO AUTOIMMUNE 478 00:20:51,023 --> 00:20:51,991 PHENOMENON, AND OF COURSE WE 479 00:20:51,991 --> 00:20:57,596 WANT TO ENABLE A QUICK 480 00:20:57,596 --> 00:21:00,199 HEMATOPOIETIC RECONSTITUTION AND 481 00:21:00,199 --> 00:21:02,401 ENGRAFTMENT OF THE TRANSPLANTED 482 00:21:02,401 --> 00:21:04,136 NOT ONLY MARROW BUT ALSO OF 483 00:21:04,136 --> 00:21:13,212 THE -- OF ALL CELLS. 484 00:21:13,212 --> 00:21:14,981 SO IN THE PAST THE CLASSICAL 485 00:21:14,981 --> 00:21:16,716 CONDITIONING REGIMEN BEFORE AN 486 00:21:16,716 --> 00:21:17,683 ALLOGENIC STEM CELL 487 00:21:17,683 --> 00:21:19,352 TRANSPLANTATION USUALLY 488 00:21:19,352 --> 00:21:23,189 CONSISTED OF A COMBINATION OF 489 00:21:23,189 --> 00:21:26,993 BUSULFAN AND CYCLOPHOSPHAMIDE. 490 00:21:26,993 --> 00:21:34,033 BUSULFAN IS AN ALKYLATING AGENT, 491 00:21:34,033 --> 00:21:38,938 HAVING -- AS BACKBONE TOGETHER 492 00:21:38,938 --> 00:21:44,276 WITH -- WITHBUTANE, HIGHLY TOXIY 493 00:21:44,276 --> 00:21:45,878 FOR STEM CELL BUT OTHER BONE 494 00:21:45,878 --> 00:21:48,714 MARROW AND BLOOD CELLS. 495 00:21:48,714 --> 00:21:52,585 CYCLOPHOSPHAMIDE IS ALSO AN DNA 496 00:21:52,585 --> 00:21:56,822 REPLICATION AGENT, LEADING TO 497 00:21:56,822 --> 00:21:58,357 ALKYLATION OF THE CELLS. 498 00:21:58,357 --> 00:22:01,727 AND IN THE LAST LET'S SAY 10 TO 499 00:22:01,727 --> 00:22:06,799 15 YEARS, LESS TOXIC WITH LESS 500 00:22:06,799 --> 00:22:11,070 ACUTE AND CHRONIC LATE EFFECTS 501 00:22:11,070 --> 00:22:13,906 TURNED OUT TO BE VERY EFFICIENT 502 00:22:13,906 --> 00:22:18,077 THAT IS A COMBINATION OF 503 00:22:18,077 --> 00:22:25,484 BUSULFAN AND FLUDARABINE. 504 00:22:25,484 --> 00:22:26,685 NOW WE HAVE A THIRD PLAYER WHICH 505 00:22:26,685 --> 00:22:29,855 IS CALLED THE LITTLE SISTER OF 506 00:22:29,855 --> 00:22:30,856 BUSULFAN. 507 00:22:30,856 --> 00:22:34,860 IT IS TR IOS ULFAN, IT IS ALSO 508 00:22:34,860 --> 00:22:37,296 OF COURSE AN ALKYLATER AND IT 509 00:22:37,296 --> 00:22:39,265 HAS SIMILAR FUNCTION AS BUSULFAN 510 00:22:39,265 --> 00:22:44,804 BUT IS MORE STABLE IN ACTION AND 511 00:22:44,804 --> 00:22:51,377 IS NOT SO MUCH INTERACTING ALSO 512 00:22:51,377 --> 00:22:52,812 WITH OTHER DRUGS. 513 00:22:52,812 --> 00:22:56,649 AND THIOTEPA IS BASED ON A BIG 514 00:22:56,649 --> 00:23:01,454 PHOSPHOROUS ATOM WHICH ALSO 515 00:23:01,454 --> 00:23:03,522 LEADS TO DESTRUCTION OF BONE 516 00:23:03,522 --> 00:23:08,694 MARROW CELLS AND STEM CELLS BUT 517 00:23:08,694 --> 00:23:09,929 IS ALSO PENETRATING THE BRAIN, 518 00:23:09,929 --> 00:23:13,532 WHICH MIGHT BE A POSSIBILITY 519 00:23:13,532 --> 00:23:16,502 ESPECIALLY MALIGNANT DISEASES TO 520 00:23:16,502 --> 00:23:18,971 AUGMENT THE CYTOTOXICS EFFICACY 521 00:23:18,971 --> 00:23:29,248 OF THOSE DRUGS. 522 00:23:30,082 --> 00:23:30,516 SOME WORDS ABOUT 523 00:23:30,516 --> 00:23:31,984 THE DONOR ISSUE. 524 00:23:31,984 --> 00:23:33,652 THE GOLD STANDARD SO FAR AND 525 00:23:33,652 --> 00:23:37,223 PERHAPS IT MIGHT CHANGE IN 526 00:23:37,223 --> 00:23:38,958 FUTURE, IS A HEMATOPOIETIC 527 00:23:38,958 --> 00:23:39,758 TRANSPLANTATION FROM MATCHED 528 00:23:39,758 --> 00:23:43,596 SIBLING DONORS, AND HERE YOU CAN 529 00:23:43,596 --> 00:23:44,997 SEE THE OUTCOME OF PATIENTS WHO 530 00:23:44,997 --> 00:23:48,934 WERE TRANSPLANTED BETWEEN 531 00:23:48,934 --> 00:23:53,305 '86 AND 2013, WHERE WE HAD A 532 00:23:53,305 --> 00:23:57,810 5-YEAR EVENT -- OF 70%. 533 00:23:57,810 --> 00:24:00,212 AND OF COURSE STEM CELL SOURCE 534 00:24:00,212 --> 00:24:00,646 MATTERS. 535 00:24:00,646 --> 00:24:05,251 WE HAD BETTER RESULTS WITH 536 00:24:05,251 --> 00:24:06,785 PERIPHERAL -- WITH CORD BLOOD 537 00:24:06,785 --> 00:24:09,088 FROM SIBLING DONORS AND BONE 538 00:24:09,088 --> 00:24:13,225 MARROW COMPARED TO -- STEM 539 00:24:13,225 --> 00:24:13,659 CELLS. 540 00:24:13,659 --> 00:24:14,527 WHY? 541 00:24:14,527 --> 00:24:17,830 BECAUSE THIS RESULTS IN A HIGHER 542 00:24:17,830 --> 00:24:21,634 INCIDENCE OF ACUTE AND CHRONIC 543 00:24:21,634 --> 00:24:22,201 GRAFT-VERSUS-HOST DISEASE. 544 00:24:22,201 --> 00:24:23,736 AND THE SECOND IMPORTANT 545 00:24:23,736 --> 00:24:27,006 OBSERVATION OF THIS WORK IS THE 546 00:24:27,006 --> 00:24:29,074 OVERALL SURVIVAL ACCORDING TO 547 00:24:29,074 --> 00:24:31,510 AGE, WHERE WE CAN SEE IT IS 548 00:24:31,510 --> 00:24:34,213 BETTER TO TRANSPLANT PATIENTS 549 00:24:34,213 --> 00:24:36,949 BEFORE THE AGE OF 16, I WOULD 550 00:24:36,949 --> 00:24:40,019 SAY BEFORE PUBERTY, BECAUSE HERE 551 00:24:40,019 --> 00:24:44,290 WE HAVE LESS SEVERE TOXICITY, WE 552 00:24:44,290 --> 00:24:46,025 HAVE LESS SEVERE GRAFT VERSUS 553 00:24:46,025 --> 00:24:48,093 HOST DISEASE, AND PERHAPS WE 554 00:24:48,093 --> 00:24:52,765 MIGHT ALSO, AS WE HEARD BEFORE, 555 00:24:52,765 --> 00:24:53,599 SAVED FERTILITY IN SOME 556 00:24:53,599 --> 00:24:58,404 PATIENTS. 557 00:24:58,404 --> 00:24:59,872 THE OTHER PROBLEM, OF COURSE, IS 558 00:24:59,872 --> 00:25:02,141 THAT MATCHED SIBLING DONORS ARE 559 00:25:02,141 --> 00:25:04,310 ONLY AVAILABLE IN 20% OF 560 00:25:04,310 --> 00:25:06,579 PATIENTS, AND IN EUROPE IT'S NOW 561 00:25:06,579 --> 00:25:09,315 A PROSPECTIVE STUDY UNDERWAY 562 00:25:09,315 --> 00:25:13,052 WHERE WE COMPARE MATCHED SIBLING 563 00:25:13,052 --> 00:25:15,554 DONOR TRANSPLANTATION WITH 564 00:25:15,554 --> 00:25:18,290 ALTERNATIVE TRANSPLANTATION FROM 565 00:25:18,290 --> 00:25:19,592 HAPLOIDENTICAL DONOR. 566 00:25:19,592 --> 00:25:23,329 AS I HAD SAID BEFORE, AGE 567 00:25:23,329 --> 00:25:24,964 MATTERS, BECAUSE WE HAVE 568 00:25:24,964 --> 00:25:28,601 INCREASED TREATMENT-RELATED 569 00:25:28,601 --> 00:25:30,603 MOTILITY DUE TO MORE INFECTIOUS 570 00:25:30,603 --> 00:25:34,940 COMPLICATIONS IN OLDER PATIENTS, 571 00:25:34,940 --> 00:25:41,413 AND IMMUNIZATION GRAFT 572 00:25:41,413 --> 00:25:43,849 REJECTION, ENCEPHALOPATHY 573 00:25:43,849 --> 00:25:46,085 SYNDROME AND OTHER CEREBRAL 574 00:25:46,085 --> 00:25:48,420 VASCULAR COMPLICATIONS, THE IRON 575 00:25:48,420 --> 00:25:50,256 OVERLOAD INCREASES OVER TIME 576 00:25:50,256 --> 00:25:51,890 DESPITE CHELATION THERAPY. 577 00:25:51,890 --> 00:25:54,627 WE HAVE MORE RISK FOR 578 00:25:54,627 --> 00:25:55,527 VENOOCCLUSIVE DISEASE, 579 00:25:55,527 --> 00:25:58,964 ESPECIALLY IN PATIENTS WHO HAVE 580 00:25:58,964 --> 00:26:00,766 PRE-EXISTING LIVER 581 00:26:00,766 --> 00:26:04,803 COMPLICATIONS, AND ALSO 582 00:26:04,803 --> 00:26:07,473 NEPHROPATHY AND OTHER SICKLE 583 00:26:07,473 --> 00:26:08,874 CELL DISEASE-RELATED 584 00:26:08,874 --> 00:26:09,475 COMPLICATIONS INCREASE OVER 585 00:26:09,475 --> 00:26:10,175 TIME. 586 00:26:10,175 --> 00:26:16,081 SO FOR US, THE BEST AGE TO BE 587 00:26:16,081 --> 00:26:19,351 TRANSPLANTED IS, LET'S SAY, 588 00:26:19,351 --> 00:26:29,862 BETWEEN 3 YEARS AND 13 YEARS. 589 00:26:32,998 --> 00:26:35,000 WE NOW HAVE INVESTIGATED ON A 590 00:26:35,000 --> 00:26:39,838 EUROPEAN LEVEL THE INFLUENCE OF 591 00:26:39,838 --> 00:26:47,346 BUSULFAN FLUDARABINE OR 592 00:26:47,346 --> 00:26:49,548 TREOSULFAN-FLUDARABINE BASED 593 00:26:49,548 --> 00:26:50,849 CONDITIONING IN TRANS PLANTED 594 00:26:50,849 --> 00:26:53,986 PATIENTS BETWEEN 2010 AND 2020 595 00:26:53,986 --> 00:26:55,954 BELOW THE AGE OF 18 YEARS WHO 596 00:26:55,954 --> 00:26:59,892 HAD THE FIRST AALLO TRANSPLANT 597 00:26:59,892 --> 00:27:02,795 WITH A MATCHED SIBLING DONOR AND 598 00:27:02,795 --> 00:27:05,164 UNDERWENT A MYELOCONDITIONING 599 00:27:05,164 --> 00:27:07,800 REGIMEN WITH EITHER BUY SUL FAN 600 00:27:07,800 --> 00:27:08,667 OR TREOSULFAN. 601 00:27:08,667 --> 00:27:13,005 WE HAVE PUBLISHED THIS INCLUDING 602 00:27:13,005 --> 00:27:15,808 A COMMENTARY. 603 00:27:15,808 --> 00:27:20,446 THE PATIENT CHARACTERISTICS WERE 604 00:27:20,446 --> 00:27:22,715 COMPARABLE WITH HAVING LITTLE 605 00:27:22,715 --> 00:27:25,784 DIFFERENCE IN THE YEAR OF 606 00:27:25,784 --> 00:27:27,553 TRANSPLANT WITH HAVING YOUNG 607 00:27:27,553 --> 00:27:29,088 PATIENTS IN THE TREO GROUP AND 608 00:27:29,088 --> 00:27:31,757 WITH HAVING MORE FEMALE PATIENTS 609 00:27:31,757 --> 00:27:34,760 IN THE TREO GROUP AND WE HAD 610 00:27:34,760 --> 00:27:38,464 MORE FEMALE TO MALE PATIENT 611 00:27:38,464 --> 00:27:41,100 TRANSPLANTS ALSO IN THE TREO 612 00:27:41,100 --> 00:27:47,439 GROUP. 613 00:27:47,439 --> 00:27:49,408 ONE INTERESTING SITUATION WAS 614 00:27:49,408 --> 00:27:53,479 THAT IN THE TREOSULFAN GROUP, 615 00:27:53,479 --> 00:27:54,913 MORE PATIENTS RECEIVED -- 616 00:27:54,913 --> 00:28:03,188 COMPARED TO THE BUSULFAN GROUP, 617 00:28:03,188 --> 00:28:04,723 MATURITY WAS PERFORMED IN 618 00:28:04,723 --> 00:28:13,031 EUROPEAN COUNTRIES AND THE 619 00:28:13,031 --> 00:28:14,333 BUSULFAN FLUDARABINE GROUP HAD 620 00:28:14,333 --> 00:28:15,334 CONTRIBUTION FROM EUROPEAN 621 00:28:15,334 --> 00:28:18,837 COUNTRIES. 622 00:28:18,837 --> 00:28:20,472 ENGRAFTMENT, OF COURSE, IS 623 00:28:20,472 --> 00:28:21,540 IMPORTANT. 624 00:28:21,540 --> 00:28:24,309 WE HAD TWO YEARS INCIDENCE OF 625 00:28:24,309 --> 00:28:26,044 SECONDARY GRAFT FAILURE 626 00:28:26,044 --> 00:28:31,116 COMPARABLE IN TWO GROUPS. 627 00:28:31,116 --> 00:28:32,751 THE INCIDENCE OF SECOND 628 00:28:32,751 --> 00:28:34,686 TRANSPLANT, THE NECESSITY OF 629 00:28:34,686 --> 00:28:36,321 SECOND TRANSPLANT WAS LOW IN 630 00:28:36,321 --> 00:28:39,057 BOTH GROUPS. 631 00:28:39,057 --> 00:28:42,327 AND IN THE BU-FLU GROUP, WE HAD 632 00:28:42,327 --> 00:28:45,431 VERY FEW PATIENTS WHO DIED AFTER 633 00:28:45,431 --> 00:28:47,566 THE FIRST TRANSPLANTATION, ONLY 634 00:28:47,566 --> 00:28:50,202 ONE DUE TO AN INFECTION 635 00:28:50,202 --> 00:28:55,140 ASSOCIATED MULTIORGAN FAILURE 636 00:28:55,140 --> 00:28:56,742 AND WE HAD SOME PATIENTS WITH 637 00:28:56,742 --> 00:28:57,910 EARLY AND SOME PATIENTS WITH 638 00:28:57,910 --> 00:28:58,811 LATE GRAFT FAILURE. 639 00:28:58,811 --> 00:29:00,746 ALL IN ALL, THE ENGRAFTMENT WAS 640 00:29:00,746 --> 00:29:06,452 GOOD IN BOTH GROUPS. 641 00:29:06,452 --> 00:29:08,086 HERE ARE THE OUTCOME DETAILS. 642 00:29:08,086 --> 00:29:11,490 AS YOU CAN SEE HERE, ONLY VERY 643 00:29:11,490 --> 00:29:13,459 FEW SIGNIFICANT DIFFERENCES. 644 00:29:13,459 --> 00:29:20,098 FOR INSTANCE, THE OVERALL 645 00:29:20,098 --> 00:29:21,600 INCIDENCE OF GRAFT-VERSUS-HOST 646 00:29:21,600 --> 00:29:26,338 DISEASE WHICH WAS A LITTLE BIT 647 00:29:26,338 --> 00:29:28,974 INCREASED IN THE TREO GROUP BUT 648 00:29:28,974 --> 00:29:30,175 EXTENSIVE CHRONIC 649 00:29:30,175 --> 00:29:33,245 GRAFT-VERSUS-HOST DISEASE WAS 650 00:29:33,245 --> 00:29:35,414 NOT SO DIFFERENT AS COMPARED TO 651 00:29:35,414 --> 00:29:42,788 OTHER FACTORS. 652 00:29:42,788 --> 00:29:44,556 HERE YOU SEE THE OVERALL 653 00:29:44,556 --> 00:29:47,726 SURVIVAL WHAT IS REALLY 654 00:29:47,726 --> 00:29:49,561 EXCELLENT. 655 00:29:49,561 --> 00:29:53,532 IN BOTH MYELOABLATIVE 656 00:29:53,532 --> 00:29:54,266 CONDITIONING REGIMEN AND ALSO 657 00:29:54,266 --> 00:29:56,034 THE INCIDENCE OF SECOND 658 00:29:56,034 --> 00:30:02,541 TRANSPLANTS WAS QUITE LOW. 659 00:30:02,541 --> 00:30:08,080 HERE YOU HAVE AN OVERVIEW WITH A 660 00:30:08,080 --> 00:30:13,452 COMPARISON OF THE TWO DIFFERENT 661 00:30:13,452 --> 00:30:14,119 CONDITIONING REGIMENS. 662 00:30:14,119 --> 00:30:15,387 AS YOU CAN SEE THE TWO YEARS 663 00:30:15,387 --> 00:30:18,657 OVERALL SURVIVAL IS MORE THAN 664 00:30:18,657 --> 00:30:22,494 99% IN BOTH GROUPS, WITH A VERY 665 00:30:22,494 --> 00:30:26,365 LOW INCIDENCE OF SEVERE 666 00:30:26,365 --> 00:30:27,132 GRAFT-VERSUS-HOST DISEASE AND 667 00:30:27,132 --> 00:30:28,734 ALSO OF CHRONIC 668 00:30:28,734 --> 00:30:30,168 GRAFT-VERSUS-HOST DISEASE, AND 669 00:30:30,168 --> 00:30:33,438 THE INCIDENCE OF LATE SECONDARY 670 00:30:33,438 --> 00:30:37,276 GRAFT FAILURES IS BELOW 10%. 671 00:30:37,276 --> 00:30:40,445 SO WHAT WE CONCLUDE IN THIS 672 00:30:40,445 --> 00:30:43,615 PAPER IS THAT BOTH CONDITIONING 673 00:30:43,615 --> 00:30:45,284 REGIMENS ENDED IN EXCELLENT 674 00:30:45,284 --> 00:30:46,818 OVERALL SURVIVAL WITH LOW RATES 675 00:30:46,818 --> 00:30:49,755 OF ACUTE AND CHRONIC 676 00:30:49,755 --> 00:30:50,489 GRAFT-VERSUS-HOST DISEASE AND 677 00:30:50,489 --> 00:30:54,359 GRAFT FAILURE. 678 00:30:54,359 --> 00:30:55,994 SO WHAT CAN WE LEARN FROM THAT? 679 00:30:55,994 --> 00:30:59,498 UNFORTUNATELY WE HAVE NOT ENOUGH 680 00:30:59,498 --> 00:31:02,534 DETAILS ON THE INCIDENCE OF 681 00:31:02,534 --> 00:31:05,604 SEVERE AND CHRONIC 682 00:31:05,604 --> 00:31:09,007 GRAFT-VERSUS-HOST DISEASE IN 683 00:31:09,007 --> 00:31:12,377 COMPARISON WITH THE 684 00:31:12,377 --> 00:31:15,547 PRE-TREATPRE-TREATMENT OF GVHD S 685 00:31:15,547 --> 00:31:16,181 QUITE INTERESTING BECAUSE IT 686 00:31:16,181 --> 00:31:18,517 MIGHT HAVE ADDITIONAL SIDE 687 00:31:18,517 --> 00:31:21,720 EFFECTS ON ENGRAFTMENT, 688 00:31:21,720 --> 00:31:22,521 LYMPHOCYTE FUNCTION AND 689 00:31:22,521 --> 00:31:25,190 POSSIBILITIES TO GET AS QUICK AS 690 00:31:25,190 --> 00:31:28,360 POSSIBLE THE GRAFT IN. 691 00:31:28,360 --> 00:31:31,763 HOWEVER, IN EUROPE, I CAN SAY 692 00:31:31,763 --> 00:31:34,833 THAT THE FAVORABLE OVERALL 693 00:31:34,833 --> 00:31:36,335 SURVIVAL, A GOOD 694 00:31:36,335 --> 00:31:38,870 GRAFT-VERSUS-HOST DISEASE 695 00:31:38,870 --> 00:31:46,945 PROFILE IS IN THE TREO-FLU 696 00:31:46,945 --> 00:31:51,783 GROUP, IN MOST CASES THIOTEPA IS 697 00:31:51,783 --> 00:31:53,318 EXCELLENT AND LED TO THE USE OF 698 00:31:53,318 --> 00:31:57,689 THIS TRIPLE MYELOABLATIVE 699 00:31:57,689 --> 00:31:58,590 CONDITIONING REGIMEN, AND WE 700 00:31:58,590 --> 00:32:01,727 WILL BE HAPPY TO INVESTIGATE 701 00:32:01,727 --> 00:32:02,928 PROSPECTIVELY THE LONG TERM 702 00:32:02,928 --> 00:32:07,199 GRAFT FUNCTION, THE TOXICITY 703 00:32:07,199 --> 00:32:09,167 PROFILE OF COURSE INCLUDING 704 00:32:09,167 --> 00:32:11,570 FERTILITY QUESTIONS AND ALSO 705 00:32:11,570 --> 00:32:15,440 GROWTH RETARDATION AND PERHAPS 706 00:32:15,440 --> 00:32:17,042 SECONDARY MALIGNANCIES IF THEY 707 00:32:17,042 --> 00:32:23,482 OCCUR IN ANY CASE. 708 00:32:23,482 --> 00:32:24,583 IT'S NOW TIME TO SAY THANK YOU. 709 00:32:24,583 --> 00:32:34,993 OF COURSE MY COLLEAGUES AND MY 710 00:32:34,993 --> 00:32:37,295 CO-AUTHOR AND THE STATISTICIAN 711 00:32:37,295 --> 00:32:39,665 OF THE EBMT, THE PARTICIPATING 712 00:32:39,665 --> 00:32:40,565 CENTERS, AND PATIENTS AND 713 00:32:40,565 --> 00:32:40,832 FAMILIES. 714 00:32:40,832 --> 00:32:45,270 THANK YOU. 715 00:32:45,270 --> 00:32:47,305 >> THANK YOU, DR. PETERS. 716 00:32:47,305 --> 00:32:48,573 FOR THE SAKE OF TIME, WE'RE 717 00:32:48,573 --> 00:32:49,841 GOING TO ASK THAT QUESTIONS BE 718 00:32:49,841 --> 00:32:51,610 POSTED IN THE CHAT. 719 00:32:51,610 --> 00:32:53,345 AND DR. PETERS, IF YOU CAN 720 00:32:53,345 --> 00:32:54,646 RESPOND TO THEM THEN. 721 00:32:54,646 --> 00:32:57,816 SO THAT WE CAN KEEP MOVING 722 00:32:57,816 --> 00:33:01,453 THROUGH OUR TIGHT SCHEDULE. 723 00:33:01,453 --> 00:33:02,354 >> THANK YOU. 724 00:33:02,354 --> 00:33:03,855 CONTINUING ON THE THEME OF POST 725 00:33:03,855 --> 00:33:06,558 TRANSPLANT SEQUELAE IS THE 726 00:33:06,558 --> 00:33:08,994 IMPORTANT QUESTION OF WHAT 727 00:33:08,994 --> 00:33:12,464 HAPPENS TO PAIN AFTER 728 00:33:12,464 --> 00:33:13,331 TRANSPLANTATION FOR SICKLE CELL 729 00:33:13,331 --> 00:33:13,565 DISEASE. 730 00:33:13,565 --> 00:33:17,436 TO SPEAK TO US ABOUT INCIDENCE 731 00:33:17,436 --> 00:33:20,238 AND RISK FACTORS FOR VOC AFTER 732 00:33:20,238 --> 00:33:25,577 TRANSPLANTATION, PLEASE WELCOME 733 00:33:25,577 --> 00:33:29,548 DR. VINEETHA NALLAGA TLA. 734 00:33:29,548 --> 00:33:31,516 SHE STARTED HER INTERNSHIP ABOUT 735 00:33:31,516 --> 00:33:34,152 TWO WEEKS AGO SO THANK YOU FOR 736 00:33:34,152 --> 00:33:35,787 TAKING TIME OUT FROM YOUR 737 00:33:35,787 --> 00:33:36,521 ROTATION TO BE WITH US. 738 00:33:36,521 --> 00:33:37,656 >> THANK YOU FOR THAT, AND THANK 739 00:33:37,656 --> 00:33:41,026 YOU FOR THIS OPPORTUNITY TODAY. 740 00:33:41,026 --> 00:33:44,896 SO I AM HERE TO SPEAK ON OUR 741 00:33:44,896 --> 00:33:47,165 PAPER ON THE INCIDENCE AND RISK 742 00:33:47,165 --> 00:33:49,901 FACTORS OF PAIN CRISIS AFTER 743 00:33:49,901 --> 00:33:51,403 HEMATOPOIETIC CELL TRANSPLANT 744 00:33:51,403 --> 00:33:58,677 FOR SICKLE CELL DISEASE. 745 00:33:58,677 --> 00:34:00,746 RECURRENT VOC OR PAIN CRIES SEES 746 00:34:00,746 --> 00:34:03,115 HAVE EMERGED AS A PRIMARY REASON 747 00:34:03,115 --> 00:34:06,351 FOR PATIENTS UNDERGOING ECT FOR 748 00:34:06,351 --> 00:34:07,619 SICKLE CELL DISEASE. 749 00:34:07,619 --> 00:34:09,054 SEVERAL REPORT A DECREASE IN THE 750 00:34:09,054 --> 00:34:11,123 HEALTHCARE USE FOR PAIN CRISES 751 00:34:11,123 --> 00:34:12,991 AS WELL AS A DECREASE IN THE USE 752 00:34:12,991 --> 00:34:15,093 OF OPIOIDS AFTER A SUCCESSFUL 753 00:34:15,093 --> 00:34:18,029 TRANSPLANT. 754 00:34:18,029 --> 00:34:18,797 HOWEVER, SICKLE CELL DISEASE 755 00:34:18,797 --> 00:34:20,532 PATIENTS MAY CONTINUE TO SUFFER 756 00:34:20,532 --> 00:34:22,300 FROM OTHER CHRONIC PAIN 757 00:34:22,300 --> 00:34:24,703 SYNDROMES AS WELL. 758 00:34:24,703 --> 00:34:26,772 AS THUS ELIMINATION OF PAIN 759 00:34:26,772 --> 00:34:32,644 CRISES AFTER TRANSPLANT IS A 760 00:34:32,644 --> 00:34:33,311 CRUCIAL PATIENT-CENTERED OUTCOME 761 00:34:33,311 --> 00:34:34,946 AND HELPS BETTER UNDERSTAND THE 762 00:34:34,946 --> 00:34:36,381 NATURAL HISTORY OF OTHER CHRONIC 763 00:34:36,381 --> 00:34:38,016 PAIN SYNDROMES AS WELL. 764 00:34:38,016 --> 00:34:40,752 WITH THAT, THE AIM OF OUR STUDY 765 00:34:40,752 --> 00:34:43,054 WAS TO DETERMINE THE INCIDENCE 766 00:34:43,054 --> 00:34:46,091 AND PREDICTIVE FACTORS OF 767 00:34:46,091 --> 00:34:48,326 RECURRENT PAIN CRISIS AFTER HCT 768 00:34:48,326 --> 00:34:54,633 IN SICKLE CELL DISEASE. 769 00:34:54,633 --> 00:34:57,035 AS WAS A RETROSPECTIVE 770 00:34:57,035 --> 00:34:59,137 REGISTRY-BASED STUDY OF PATIENTS 771 00:34:59,137 --> 00:35:00,405 UNDERGOING HCT FOR SICKLE CELL 772 00:35:00,405 --> 00:35:05,477 DISEASE BETWEEN 1991 TO 2021, IN 773 00:35:05,477 --> 00:35:08,013 THE UNITED STATES WITH DATA 774 00:35:08,013 --> 00:35:09,948 SUBMITTED TO THE REGISTRY, THE 775 00:35:09,948 --> 00:35:10,816 DE-IDENTIFIED DATASET WAS 776 00:35:10,816 --> 00:35:17,722 OBTAINED THROUGH THE NHLBI BAY 777 00:35:17,722 --> 00:35:25,463 BIOLINCC HOSTED ON THE URL 778 00:35:25,463 --> 00:35:26,031 CURESICKLECELL.RTI.ORG. 779 00:35:26,031 --> 00:35:28,466 DATA WAS COLLECTED AT 3, 6, 12 780 00:35:28,466 --> 00:35:30,302 AND 24 MONTHS AFTER HCT AND 781 00:35:30,302 --> 00:35:31,369 EVERY TWO YEARS UNTIL DEATH, 782 00:35:31,369 --> 00:35:33,038 LOSS TO FOLLOW-UP. 783 00:35:33,038 --> 00:35:35,440 PATIENTS WERE ASSIGNED TO EITHER 784 00:35:35,440 --> 00:35:43,315 THE TED TRACK OR COMPREHENSIVE 785 00:35:43,315 --> 00:35:46,818 OR CRF TRACK WHICH COLLECTED 786 00:35:46,818 --> 00:35:50,222 DETAILED DISEASE, OR 787 00:35:50,222 --> 00:35:53,091 TREATMENT-RELATED DATA. 788 00:35:53,091 --> 00:35:55,360 FORM 2030, WHICH IS THE SICKLE 789 00:35:55,360 --> 00:35:57,229 CELL DISEASE PREINFUSION FORM, A 790 00:35:57,229 --> 00:36:01,166 TYPE OF CRF TRACK FORM, ASKED 791 00:36:01,166 --> 00:36:03,401 QUESTIONS ON WHETHER 792 00:36:03,401 --> 00:36:04,236 VASO-OCCLUSIVE PAIN REQUIRING 793 00:36:04,236 --> 00:36:05,537 HOSPITALIZATION OCCURRED WITHIN 794 00:36:05,537 --> 00:36:09,341 THE TWO YEARS PRIOR TO THE 795 00:36:09,341 --> 00:36:10,075 TRANSPLANT, AS WELL AS SPECIFIES 796 00:36:10,075 --> 00:36:12,544 THE FREQUENCIES. 797 00:36:12,544 --> 00:36:14,746 FORM 2130, WHICH IS THE SICKLE 798 00:36:14,746 --> 00:36:16,381 CELL DISEASE POST HCT FOLLOW-UP 799 00:36:16,381 --> 00:36:20,185 FORM, ASKED QUESTIONS ON THE 800 00:36:20,185 --> 00:36:22,153 OCCURRENCE OF VASO-OCCLUSIVE 801 00:36:22,153 --> 00:36:23,355 PAIN POST TRANSPLANT AND THE 802 00:36:23,355 --> 00:36:26,992 FREQUENCY. 803 00:36:26,992 --> 00:36:28,393 A VASO-OCCLUSIVE EPISODE WAS 804 00:36:28,393 --> 00:36:31,129 DEFINED AS ANY PAIN WHICH WAS 805 00:36:31,129 --> 00:36:32,764 REQUIRING HOSPITALIZATION OR 806 00:36:32,764 --> 00:36:36,368 TREATMENT, THAT IS IN THE 807 00:36:36,368 --> 00:36:37,402 EMERGENCY ROOM, A DAY HOSPITAL 808 00:36:37,402 --> 00:36:38,470 OR INPATIENT ADMISSION. 809 00:36:38,470 --> 00:36:42,073 THERE WAS NO CAPTURE OF ANY 810 00:36:42,073 --> 00:36:44,376 PATIENT-REPORTED VASO-OCCLUSIVE 811 00:36:44,376 --> 00:36:46,578 CRISES OUTSIDE THE HOSPITAL 812 00:36:46,578 --> 00:36:47,979 SETTING, NOR WAS THERE DATA 813 00:36:47,979 --> 00:36:50,815 REGARDING THE TREATMENT OR THE 814 00:36:50,815 --> 00:36:51,716 TIME POINT OF OCCURRENCE OF 815 00:36:51,716 --> 00:36:58,590 THESE EPISODES POST TRANSPLANT. 816 00:36:58,590 --> 00:37:01,559 THE DATA COLLECTED WAS ANALYZED 817 00:37:01,559 --> 00:37:04,396 BY UNIVARIABLE AND MULTIVARIABLE 818 00:37:04,396 --> 00:37:06,698 LOGISTIC REGRESSION MODELS USING 819 00:37:06,698 --> 00:37:09,067 BACKWARD SELECTION PROCEDURES. 820 00:37:09,067 --> 00:37:12,137 TWO MODELS WERE DEVELOPED, ONE 821 00:37:12,137 --> 00:37:13,772 FOCUSING ON ONLY THE 822 00:37:13,772 --> 00:37:17,008 PRETRANSPLANT FACTORS, AND THE 823 00:37:17,008 --> 00:37:18,376 SECOND INCLUDING ALSO THE POST 824 00:37:18,376 --> 00:37:20,245 TRANSPLANT FACTORS. 825 00:37:20,245 --> 00:37:23,315 A PREDICTIVE NORMALGRAM WAS 826 00:37:23,315 --> 00:37:25,150 CREATED TO VISUALLY EXAMINE THE 827 00:37:25,150 --> 00:37:26,251 RELATIONSHIP BETWEEN THE VARIOUS 828 00:37:26,251 --> 00:37:28,253 FACTORS AND THE OCCURRENCE OF 829 00:37:28,253 --> 00:37:35,593 PAIN CRISIS. 830 00:37:35,593 --> 00:37:38,663 OUT OF THE TOTAL 1,718 PATIENTS 831 00:37:38,663 --> 00:37:40,799 WHO UNDERWENT TRANSPLANT BETWEEN 832 00:37:40,799 --> 00:37:48,606 1991 TO 2021, 1453 PATIENTS 833 00:37:48,606 --> 00:37:50,308 UNDERWENT TRANS PLAIN FROM 2008 834 00:37:50,308 --> 00:37:53,611 TO 2021 WITH 763 ASSIGNED TO THE 835 00:37:53,611 --> 00:37:56,448 CRF TRACK WITH DATA REPORTED ON 836 00:37:56,448 --> 00:37:58,083 THE OCCURRENCE OF VASO-OCCLUSIVE 837 00:37:58,083 --> 00:37:59,617 CRISIS AS A YES OR A NO. 838 00:37:59,617 --> 00:38:03,455 THE REMAINDER OF THE PATIENTS 839 00:38:03,455 --> 00:38:04,956 HAD NO DATA AVAILABLE OR HAD A 840 00:38:04,956 --> 00:38:05,991 VALUE OF UNKNOWN. 841 00:38:05,991 --> 00:38:11,096 OUT OF THE TOTAL 763 PATIENT, 66 842 00:38:11,096 --> 00:38:13,498 PATIENTS HAD PAIN CRISIS POST 843 00:38:13,498 --> 00:38:15,367 TRANSPLANT, OF WHICH 41 HAD 844 00:38:15,367 --> 00:38:20,505 GRAFT FAILURE AND 25 HAD STABLE 845 00:38:20,505 --> 00:38:25,777 ENGRAFTMENT. 846 00:38:25,777 --> 00:38:28,013 IN OUR FIRST MODEL, WHICH 847 00:38:28,013 --> 00:38:31,583 INCLUDED ONLY THE PREHCT 848 00:38:31,583 --> 00:38:33,018 FACTORS, STATISTICALLY 849 00:38:33,018 --> 00:38:35,653 SIGNIFICANT PREDICTORS FOR THE 850 00:38:35,653 --> 00:38:39,924 OCCURRENCE OF VOC POST 851 00:38:39,924 --> 00:38:41,659 TRANSPLANT WERE INCREASING AGE 852 00:38:41,659 --> 00:38:44,596 AT HCT, PAIN CRISIS TWO YEARS 853 00:38:44,596 --> 00:38:47,899 PRIOR TO HCT AND A KPS SCORE AT 854 00:38:47,899 --> 00:38:48,767 LESS THAN 90. 855 00:38:48,767 --> 00:38:49,734 IN THE SECOND MODEL WHICH 856 00:38:49,734 --> 00:38:52,037 INCLUDED EVEN THE POST HCT 857 00:38:52,037 --> 00:38:53,705 FACTORS AND INCREASING AGE, A 858 00:38:53,705 --> 00:38:57,742 HISTORY OF PAIN CRISIS TWO YEARS 859 00:38:57,742 --> 00:38:59,711 PRETRANSPLANT, A KPS OF LESS 860 00:38:59,711 --> 00:39:01,012 THAN 90 AND GRAFT FAILURE TURNED 861 00:39:01,012 --> 00:39:10,488 OUT TO BE SIGNIFICANT. 862 00:39:10,488 --> 00:39:12,757 THIS IS THE FIRST NORMALGRAM 863 00:39:12,757 --> 00:39:15,427 THAT WE HAD WHICH PREDICTED THE 864 00:39:15,427 --> 00:39:18,430 PREHCT RISK OF VOC POST 865 00:39:18,430 --> 00:39:18,730 TRANSPLANT. 866 00:39:18,730 --> 00:39:21,433 SO IF WE TAKE A TEST PATIENT WHO 867 00:39:21,433 --> 00:39:26,771 IS 10 YEARS OLD WITH A WEIGHT OF 868 00:39:26,771 --> 00:39:29,307 25 KILOGRAMS WITH A HEMOGLOBIN 869 00:39:29,307 --> 00:39:31,476 OF 7 AND A KPS SCORE OF LESS 870 00:39:31,476 --> 00:39:34,746 THAN 90, WHO'S UNDERGOING A 871 00:39:34,746 --> 00:39:36,848 MISMATCHED RELATED BONE MARROW 872 00:39:36,848 --> 00:39:38,483 TRANSPLANT WITH A 873 00:39:38,483 --> 00:39:40,218 NON-MYELOABLATIVE CONDITIONING 874 00:39:40,218 --> 00:39:42,854 REGIMEN AND A HISTORY OF 875 00:39:42,854 --> 00:39:46,091 VASO-OCCLUSIVE CRISIS IN THE TWO 876 00:39:46,091 --> 00:39:47,025 YEARS PRETRANSPLANT WOULD HAVE A 877 00:39:47,025 --> 00:39:50,328 TOTAL SCORE OF 230, WHICH WOULD 878 00:39:50,328 --> 00:39:55,467 TRANSLATE TO AN APPROXIMATE POST 879 00:39:55,467 --> 00:39:58,937 TRANSPLANT VOC RISK OF 15%. 880 00:39:58,937 --> 00:40:02,974 IF THE SAME PATIENT WERE TO HAVE 881 00:40:02,974 --> 00:40:06,678 GRAFT FAILURE POST TRANSPLANT, 882 00:40:06,678 --> 00:40:09,547 HIS SCORE IN THE POST HCT 883 00:40:09,547 --> 00:40:13,384 PREDICTIVE RISK NOMOGRAM WOULD 884 00:40:13,384 --> 00:40:15,220 INCREASE TO A 259, WHICH WOULD 885 00:40:15,220 --> 00:40:23,895 TRANSLATE TO A RISK OF 34%. 886 00:40:23,895 --> 00:40:24,796 WE ACKNOWLEDGE THE LIMITATIONS 887 00:40:24,796 --> 00:40:27,732 OF A REGISTRY-BASED STUDY IN THE 888 00:40:27,732 --> 00:40:30,235 SENSE THAT THE ACCURACY OF THE 889 00:40:30,235 --> 00:40:32,103 DATA DEPENDS ON THE COMPLETENESS 890 00:40:32,103 --> 00:40:38,443 AND COLLECTION AND SUBMISSION 891 00:40:38,443 --> 00:40:41,846 DATA LACKED GRANULAR DETAILS OF 892 00:40:41,846 --> 00:40:43,448 CLINICALLY RELEVANT INFORMATION. 893 00:40:43,448 --> 00:40:45,350 THERE WAS NO DATA AVAILABLE ON 894 00:40:45,350 --> 00:40:47,285 THE PARTICULAR TIME POINT AFTER 895 00:40:47,285 --> 00:40:48,920 HCT THAT THE PAPER CRISIS 896 00:40:48,920 --> 00:40:50,021 OCCURRED, NOR WAS THERE ANY 897 00:40:50,021 --> 00:40:51,789 CAPTURE OF PAIN CRISIS OUTSIDE 898 00:40:51,789 --> 00:40:57,462 OF THE HOSPITAL SETTING. 899 00:40:57,462 --> 00:41:00,665 FURTHER THERE WERE NO DETAILS ON 900 00:41:00,665 --> 00:41:02,967 ANY NON-VASO-OCCLUSIVE PAIN 901 00:41:02,967 --> 00:41:03,935 EPISODES OR CHRONIC PAIN. 902 00:41:03,935 --> 00:41:04,969 FURTHER WE COULD NOT CROSS 903 00:41:04,969 --> 00:41:06,371 VALIDATE THE MODEL'S PERFORMANCE 904 00:41:06,371 --> 00:41:08,540 DUE TO THE SMALL NUMBER OF HCT 905 00:41:08,540 --> 00:41:09,407 PROCEDURES PERFORMED IN PATIENTS 906 00:41:09,407 --> 00:41:13,912 WITH SICKLE CELL DISEASE. 907 00:41:13,912 --> 00:41:15,647 IN CONCLUSION, OUR STUDY FOUND 908 00:41:15,647 --> 00:41:18,483 THE RECURRENCE OF PAIN CRISIS 909 00:41:18,483 --> 00:41:20,218 POST TRANSPLANT IN SICKLE CELL 910 00:41:20,218 --> 00:41:25,623 DISEASE TO BE 8-POI 8.65% WHICHS 911 00:41:25,623 --> 00:41:26,691 CORRELATED WITH THE AGE AT 912 00:41:26,691 --> 00:41:29,127 TRANSPLANT WITH THE PREHCT 913 00:41:29,127 --> 00:41:31,729 HEMOGLOBIN DONOR AND GRAFT TYPE 914 00:41:31,729 --> 00:41:33,498 CONDITIONING INTENSITY, PRIOR 915 00:41:33,498 --> 00:41:35,600 HISTORY OF PAIN CRISIS, AND THE 916 00:41:35,600 --> 00:41:38,303 OCCURRENCE OF GRAFT FAILURE. 917 00:41:38,303 --> 00:41:40,271 THERE IS A NEED FOR A MORE 918 00:41:40,271 --> 00:41:42,574 DETAILED CAPTURE OF THE 919 00:41:42,574 --> 00:41:44,876 FREQUENCY, TIMING, TREATMENT OF 920 00:41:44,876 --> 00:41:47,812 THESE EPISODES AND COLLECTION OF 921 00:41:47,812 --> 00:41:50,248 OTHER PATIENT-REPORTED OUTCOMES. 922 00:41:50,248 --> 00:41:51,749 THESE DATA CAN HELP US TO 923 00:41:51,749 --> 00:41:53,384 UNDERSTAND, PREVENT, AND REDUCE 924 00:41:53,384 --> 00:41:55,920 THE IMPACT OF HCT ON THE BURDEN 925 00:41:55,920 --> 00:41:58,356 OF THE ACUTE AND CHRONIC SICKLE 926 00:41:58,356 --> 00:42:04,829 CELL DISEASE-RELATED PAIN. 927 00:42:04,829 --> 00:42:05,263 THANK YOU. 928 00:42:05,263 --> 00:42:13,905 [APPLAUSE] 929 00:42:13,905 --> 00:42:14,539 >> THANK YOU. 930 00:42:14,539 --> 00:42:17,175 I'M SURE THERE WILL BE SOME 931 00:42:17,175 --> 00:42:18,276 INTERESTING QUESTIONS. 932 00:42:18,276 --> 00:42:24,315 PLEASE WALK UP TO THE MIC. 933 00:42:24,315 --> 00:42:25,683 >> COURTNEY FROM NIH. 934 00:42:25,683 --> 00:42:26,084 GREAT TALK. 935 00:42:26,084 --> 00:42:27,685 I JUST WANT TO KNOW HOW YOU USED 936 00:42:27,685 --> 00:42:28,886 THESE FINDINGS TO EDUCATE 937 00:42:28,886 --> 00:42:31,089 PATIENTS BEFORE THE TRANSPLANT. 938 00:42:31,089 --> 00:42:32,490 HOW TO TALK TO THEM ABOUT THE 939 00:42:32,490 --> 00:42:33,491 RISK ESPECIALLY WHEN YOU'RE 940 00:42:33,491 --> 00:42:34,592 TRYING TO TELL THEM ABOUT THE 941 00:42:34,592 --> 00:42:36,094 RISK OF PAIN AFTER THE 942 00:42:36,094 --> 00:42:40,298 SUCCESSFUL TRANSPLANT. 943 00:42:40,298 --> 00:42:45,069 >> WE HAVE NOT YET USED THE 944 00:42:45,069 --> 00:42:46,604 FINDINGS OF THE NOMOGRAM TO KIND 945 00:42:46,604 --> 00:42:50,008 OF EDUCATE THE PATIENTS, BUT 946 00:42:50,008 --> 00:42:51,309 DEFINITELY SOMETHING WE LOOK 947 00:42:51,309 --> 00:42:52,110 FORWARD TO DOING IT. 948 00:42:52,110 --> 00:42:53,044 >> THAT WAS AN EXCELLENT 949 00:42:53,044 --> 00:42:57,015 QUESTION, IF I MAY ADD, SO A 950 00:42:57,015 --> 00:42:57,849 NOMOGRAM WOULD GIVE YOU A 951 00:42:57,849 --> 00:42:59,517 GENERAL IDEA, AND I THINK THE 952 00:42:59,517 --> 00:43:01,386 GENERAL IDEA IS THAT OLDER 953 00:43:01,386 --> 00:43:02,887 PATIENTS AND PATIENTS WHO HAVE 954 00:43:02,887 --> 00:43:04,989 HAD A LOT OF VOCs MAY BE AT 955 00:43:04,989 --> 00:43:06,424 HIGHER RISK, AND PEOPLE WANT TO 956 00:43:06,424 --> 00:43:07,959 KNOW ACTUALLY WHAT THEIR OUT 957 00:43:07,959 --> 00:43:10,662 COME IS GOING TO BE. 958 00:43:10,662 --> 00:43:12,830 SO USING DATA LIKE THIS, YOU 959 00:43:12,830 --> 00:43:14,032 COULD MAKE A GENERAL PREDICTION 960 00:43:14,032 --> 00:43:15,900 THAT YOU HAVE SOME INCREASED 961 00:43:15,900 --> 00:43:19,304 CHANCE OF HAVING PERSISTENT 962 00:43:19,304 --> 00:43:20,505 PAIN. 963 00:43:20,505 --> 00:43:22,240 BUT AS YOU KNOW FROM YOUR WORK 964 00:43:22,240 --> 00:43:24,342 AND ALEXIS LEONARD'S WORK, THAT 965 00:43:24,342 --> 00:43:26,110 WITH MULTIDISCIPLINARY 966 00:43:26,110 --> 00:43:27,078 INTERVENTIONS, MOST OF THE 967 00:43:27,078 --> 00:43:30,048 PATIENTS EVENTUALLY BECOME 968 00:43:30,048 --> 00:43:32,116 PAIN-FREE. 969 00:43:32,116 --> 00:43:32,717 AGAIN, THIS INFORMATION WOULD 970 00:43:32,717 --> 00:43:33,851 HAVE TO BE PROVIDED IN THAT 971 00:43:33,851 --> 00:43:34,519 CONTEXT. 972 00:43:34,519 --> 00:43:35,386 I HOPE THAT ANSWERS YOUR 973 00:43:35,386 --> 00:43:35,953 QUESTION. 974 00:43:35,953 --> 00:43:40,425 THANK YOU. 975 00:43:40,425 --> 00:43:41,292 WE HAVE OTHER QUESTIONS. 976 00:43:41,292 --> 00:43:43,494 WAS THERE ANY WAY TO LOOK AT THE 977 00:43:43,494 --> 00:43:45,697 TIMING OF VOCs POST 978 00:43:45,697 --> 00:43:46,097 TRANSPLANT? 979 00:43:46,097 --> 00:43:48,399 DID THEY MOSTLY OCCUR SHORTLY 980 00:43:48,399 --> 00:43:49,367 AFTER TRANSPLANT OR TWO TO FIVE 981 00:43:49,367 --> 00:43:50,368 YEARS OR GREATER THAN FIVE 982 00:43:50,368 --> 00:43:50,568 YEARS? 983 00:43:50,568 --> 00:43:53,104 >> SO THE DATASET THAT WE HAD 984 00:43:53,104 --> 00:43:55,640 DID NOT TELL US THE TIMING, 985 00:43:55,640 --> 00:43:57,041 WHETHER IT WAS IN THE SHORT 986 00:43:57,041 --> 00:43:59,310 TERM, LESS THAN ONE YEAR, ONE TO 987 00:43:59,310 --> 00:44:01,312 TWO YEARS, TWO TO FIVE YEARS, SO 988 00:44:01,312 --> 00:44:02,613 THAT'S A LIMITATION THAT WE 989 00:44:02,613 --> 00:44:02,914 ACKNOWLEDGE. 990 00:44:02,914 --> 00:44:03,715 >> DR. HORWITZ. 991 00:44:03,715 --> 00:44:05,516 >> YOU ACTUALLY COULD ESTIMATE 992 00:44:05,516 --> 00:44:08,186 IT BY LOOKING AT THE DATE OF THE 993 00:44:08,186 --> 00:44:11,823 REPORTS, BECAUSE THE QUESTION 994 00:44:11,823 --> 00:44:14,592 IS, WAS THERE VOD SINCE THE LAST 995 00:44:14,592 --> 00:44:15,026 REPORT. 996 00:44:15,026 --> 00:44:17,762 SO IF YOU HAD THE DATE OF THE 997 00:44:17,762 --> 00:44:19,497 REPORTS AND THEY'RE GENERALLY 998 00:44:19,497 --> 00:44:20,932 REQUIRED EVERY YEAR AFTER A 999 00:44:20,932 --> 00:44:21,999 CERTAIN POINT, YOU COULD GET A 1000 00:44:21,999 --> 00:44:23,434 ROUGH IDEA OF WHETHER IT'S EARLY 1001 00:44:23,434 --> 00:44:25,536 OR LATE. 1002 00:44:25,536 --> 00:44:26,938 SO YOU MIGHT WANT TO LOOK AT THE 1003 00:44:26,938 --> 00:44:28,139 DATASET FOR THAT PARTICULAR 1004 00:44:28,139 --> 00:44:28,406 VARIABLE. 1005 00:44:28,406 --> 00:44:29,207 >> WE WILL, THANK YOU. 1006 00:44:29,207 --> 00:44:31,843 >> THIS IS A WONDERFUL -- WHO 1007 00:44:31,843 --> 00:44:33,311 BETTER TO ANSWER THAT QUESTION 1008 00:44:33,311 --> 00:44:38,416 THAN DR. HORWITZ HERSELF. 1009 00:44:38,416 --> 00:44:40,385 SO THE FORMS ARE ABSOLUTELY 1010 00:44:40,385 --> 00:44:42,687 TIMED, RIGHT? 1011 00:44:42,687 --> 00:44:45,423 THIS WAS A PUBLICLY AVAILABLE 1012 00:44:45,423 --> 00:44:47,725 DATASET THROUGH THE BIOLINCC, SO 1013 00:44:47,725 --> 00:44:52,663 WE'D ACTUALLY GO BACK TO THE 1014 00:44:52,663 --> 00:44:54,098 NON-MALIGNANT HEME COMMITTEE AND 1015 00:44:54,098 --> 00:44:55,600 SAY WE OUGHT TO TAKE A DEEPER 1016 00:44:55,600 --> 00:44:56,467 DIVE LOOKING AT THIS. 1017 00:44:56,467 --> 00:44:56,968 SO THANK YOU VERY MUCH. 1018 00:44:56,968 --> 00:44:59,637 WE HAVE MORE QUESTIONS. 1019 00:44:59,637 --> 00:45:03,007 >> I ALSO WANT TO POINT OUT 1020 00:45:03,007 --> 00:45:09,147 THAT -- [INAUDIBLE] 1021 00:45:09,147 --> 00:45:12,683 >> YES, THE -- THREE-POINT -- 1022 00:45:12,683 --> 00:45:14,619 ALSO COLLECTS INFORMATION ON THE 1023 00:45:14,619 --> 00:45:16,354 CHRONIC PAIN PRETRANSPLANT, SO 1024 00:45:16,354 --> 00:45:17,388 WE'RE REALLY LOOKING FORWARD TO 1025 00:45:17,388 --> 00:45:18,222 THAT. 1026 00:45:18,222 --> 00:45:22,393 >> SO MYCO-CH MY CO-CHAIR IS SAP 1027 00:45:22,393 --> 00:45:22,927 IT UP. 1028 00:45:22,927 --> 00:45:30,635 THANK YOU, DR. NALLAGATLA. 1029 00:45:30,635 --> 00:45:32,036 >> WE'LL MOVE TO OUR NEXT 1030 00:45:32,036 --> 00:45:34,205 SPEAKER, DR. ALEXIS LE IN ORDER. 1031 00:45:34,205 --> 00:45:35,840 NOW AT ST. JUDE'S CHILDREN'S 1032 00:45:35,840 --> 00:45:36,607 RESEARCH HOSPITAL WILL BE 1033 00:45:36,607 --> 00:45:38,676 PRESENTING ON IN VIVO 1034 00:45:38,676 --> 00:45:40,678 MEASUREMENT OF RBC SURVIVAL IN 1035 00:45:40,678 --> 00:45:41,846 PATIENTS WITH SICKLE CELL 1036 00:45:41,846 --> 00:45:42,980 DISEASE BEFORE AND AFTER 1037 00:45:42,980 --> 00:45:48,319 TRANSPLANT. 1038 00:45:48,319 --> 00:45:49,520 >> GOOD MORNING. 1039 00:45:49,520 --> 00:45:50,822 THANK YOU ALL FOR HAVING ME 1040 00:45:50,822 --> 00:45:51,789 TODAY. 1041 00:45:51,789 --> 00:45:53,024 AND I APOLOGIZE FOR NOT BEING 1042 00:45:53,024 --> 00:45:54,992 THERE IN PERSON. 1043 00:45:54,992 --> 00:45:56,194 I AM THRILLED TO TALK ABOUT THIS 1044 00:45:56,194 --> 00:45:58,362 WORK THAT I DID WHEN I WAS A 1045 00:45:58,362 --> 00:46:01,299 MEMBER OF THE TISDALE LAB, WHERE 1046 00:46:01,299 --> 00:46:02,967 WE LOOK AT MEASURING DIRECTLY 1047 00:46:02,967 --> 00:46:04,402 RED CELL SURVIVAL BEFORE AND 1048 00:46:04,402 --> 00:46:06,471 AFTER TRANSPLANT. 1049 00:46:06,471 --> 00:46:13,611 THESE ARE MY DISCLOSURES. 1050 00:46:13,611 --> 00:46:15,112 THANK YOU. 1051 00:46:15,112 --> 00:46:16,447 SO AS THIS AUDIENCE IS WELL 1052 00:46:16,447 --> 00:46:18,616 FAMILIAR, THE IDEA BEHIND A 1053 00:46:18,616 --> 00:46:20,384 CURATIVE STRATEGY IS TO RESTORE 1054 00:46:20,384 --> 00:46:22,453 RED CELL FUNCTION EITHER BY 1055 00:46:22,453 --> 00:46:24,322 REPLACING THE SICKLE RBCs WITH 1056 00:46:24,322 --> 00:46:25,857 THAT OF A DONOR OR IN THE CASE 1057 00:46:25,857 --> 00:46:28,259 OF GENE THERAPY, INCREASING 1058 00:46:28,259 --> 00:46:30,127 ANTISICKLING GLOBIN ENOUGH TO 1059 00:46:30,127 --> 00:46:31,896 CORRECT THE ANEMIA AND PROLONG 1060 00:46:31,896 --> 00:46:33,397 THE RED CELL SURVIVAL. 1061 00:46:33,397 --> 00:46:36,767 AND WE'VE KNOWN FOR A LONG TIME 1062 00:46:36,767 --> 00:46:37,869 THAT STABLE MIXED CHIMERISM IS 1063 00:46:37,869 --> 00:46:39,303 SUFFICIENT TO REVERSE THE 1064 00:46:39,303 --> 00:46:41,072 PHENOTYPE BASED SOLELY OF THE 1065 00:46:41,072 --> 00:46:43,140 NATURAL SURVIVAL ADVANTAGE AND 1066 00:46:43,140 --> 00:46:44,675 ENRICHMENT OF THE DONOR RED 1067 00:46:44,675 --> 00:46:47,178 CELLS. 1068 00:46:47,178 --> 00:46:48,513 SO WHEN YOU LOOK AT THE 1069 00:46:48,513 --> 00:46:51,215 RELATIONSHIP BETWEEN THE 1070 00:46:51,215 --> 00:46:52,884 CHIMERISM THAT YOU SEE IN THE 1071 00:46:52,884 --> 00:46:54,185 PERIPHERAL BLOOD, YOU SEE A TWO 1072 00:46:54,185 --> 00:46:56,153 TO FIVE FOLD ENRICHMENT OF THE 1073 00:46:56,153 --> 00:46:57,588 DONOR RED CELLS IN PATIENTS WITH 1074 00:46:57,588 --> 00:47:02,527 MIXED CHIMERISM. 1075 00:47:02,527 --> 00:47:04,695 THERE'S NEARLY FULL REPLACEMENT 1076 00:47:04,695 --> 00:47:06,130 IN THE PERIPHERAL BLOOD BY THESE 1077 00:47:06,130 --> 00:47:07,999 DONOR DERIVED MATURE RED CELLS 1078 00:47:07,999 --> 00:47:09,634 EVEN IN THE SETTING OF MIXED 1079 00:47:09,634 --> 00:47:10,935 CHIMERISM, WHICH EXPLAINS THE 1080 00:47:10,935 --> 00:47:12,904 CLINICAL AND FUNCTIONAL 1081 00:47:12,904 --> 00:47:14,438 IMPROVEMENTS, BUT AS THIS FIGURE 1082 00:47:14,438 --> 00:47:22,313 SHOWS, IT'S NOT ALWAYS 100%. 1083 00:47:22,313 --> 00:47:25,383 SO WE KNOW FROM DR. FITZHUGH'S 1084 00:47:25,383 --> 00:47:27,118 PUBLICATION ABOUT THE 20% 1085 00:47:27,118 --> 00:47:28,219 THRESHOLD THAT IN THEORY, A 1086 00:47:28,219 --> 00:47:30,087 PATIENT WHO HAS A SHORTER SICKLE 1087 00:47:30,087 --> 00:47:31,822 RED CELL LIFESPAN MAY TOLERATE A 1088 00:47:31,822 --> 00:47:36,861 LOWER DONOR MYELOID CHIMERISM TO 1089 00:47:36,861 --> 00:47:39,497 ACHIEVE EQUIVALENT FRACTION OF 1090 00:47:39,497 --> 00:47:40,731 DONOR RED BLOOD CELLS IN THE 1091 00:47:40,731 --> 00:47:41,165 PERIPHERAL BLOOD. 1092 00:47:41,165 --> 00:47:42,700 SO WE ASKED OURSELVES INSTEAD OF 1093 00:47:42,700 --> 00:47:44,268 USING AN EQUATION, COULD WE 1094 00:47:44,268 --> 00:47:45,436 ACTUALLY DIRECTLY MEASURE THE 1095 00:47:45,436 --> 00:47:47,972 RED CELL SURVIVAL, AND COULD WE 1096 00:47:47,972 --> 00:47:49,707 THEN USE VARIOUS FACTORS THAT 1097 00:47:49,707 --> 00:47:51,342 ARE MEASURABLE TO PREDICT A 1098 00:47:51,342 --> 00:47:52,543 PATIENT'S LIFESPAN AND, 1099 00:47:52,543 --> 00:47:57,148 THEREFORE, THEIR DONOR MYELOID 1100 00:47:57,148 --> 00:47:57,415 CHIMERISM. 1101 00:47:57,415 --> 00:47:59,450 CAN YOU MEASURE THIS EITHER BY 1102 00:47:59,450 --> 00:48:00,651 POPULATION STEADY WHERE YOU'RE 1103 00:48:00,651 --> 00:48:01,886 MEASURING A POPULATION OF RED 1104 00:48:01,886 --> 00:48:03,387 CELLS, NEW AND OLD, OR A COHORT 1105 00:48:03,387 --> 00:48:04,722 STUDY WHERE YOU'RE MEASURING ALL 1106 00:48:04,722 --> 00:48:07,224 RED CELLS AT THE SAME AGE. 1107 00:48:07,224 --> 00:48:08,559 AND THIS HAS BEEN DONE IN MANY 1108 00:48:08,559 --> 00:48:09,493 DIFFERENT DISORDERS. 1109 00:48:09,493 --> 00:48:11,963 BUT IT ACTUALLY HAS BEEN DONE IN 1110 00:48:11,963 --> 00:48:16,233 PATIENTS WITH SS DISEASE WITH 1111 00:48:16,233 --> 00:48:17,768 VARIOUS DIFFERENT METHODS, AND 1112 00:48:17,768 --> 00:48:21,505 YOU SEE A -- HEALTHY TRAIT. 1113 00:48:21,505 --> 00:48:25,443 AND YOU CAN SEE THESE FRACTIONAL 1114 00:48:25,443 --> 00:48:27,645 SURVIVAL CURVES COMPARED TO THE 1115 00:48:27,645 --> 00:48:30,915 NORMAL CONTROL. 1116 00:48:30,915 --> 00:48:32,316 SO THIS IS OUR STUDY. 1117 00:48:32,316 --> 00:48:34,185 YOU CAN SEE THE INCLUSION AND 1118 00:48:34,185 --> 00:48:36,253 EXCLUSION CRITERIA. 1119 00:48:36,253 --> 00:48:38,255 MEASURING THE RED CELL SURVIVAL 1120 00:48:38,255 --> 00:48:39,223 IN PATIENTS BEFORE AND AFTER 1121 00:48:39,223 --> 00:48:39,690 TRANSPLANT. 1122 00:48:39,690 --> 00:48:43,828 SO ANY ADULT WITH ANY GENOTYPE 1123 00:48:43,828 --> 00:48:45,596 OF SICKLE CELL DISEASE -- SORRY, 1124 00:48:45,596 --> 00:48:49,400 THERE'S AN ECHO -- WHO HAS 1125 00:48:49,400 --> 00:48:51,702 NORMAL RENAL FUNCTION BECAUSE 1126 00:48:51,702 --> 00:48:54,171 BIOTIN IS A WATER-SOLUBLE 1127 00:48:54,171 --> 00:48:54,805 VITAMIN. 1128 00:48:54,805 --> 00:48:58,075 AND THEN THE MAIN -- ONE OF THE 1129 00:48:58,075 --> 00:48:59,176 MAIN EXCLUSION CRITERIAS IS 1130 00:48:59,176 --> 00:49:00,378 BEING ON THE BIOTIN 1131 00:49:00,378 --> 00:49:01,345 SUPPLEMENTATION. 1132 00:49:01,345 --> 00:49:05,850 SO WE INCLUDED 20 PARTICIPANTS, 1133 00:49:05,850 --> 00:49:07,652 OF WHICH SIX WERE PRETRANSPLANT, 1134 00:49:07,652 --> 00:49:10,454 FIVE WERE POST TRANSPLANT, SIX 1135 00:49:10,454 --> 00:49:12,657 WERE AS AND THREE HAD AA. 1136 00:49:12,657 --> 00:49:15,726 HALF OF OUR COHORT HAD A SINGLE 1137 00:49:15,726 --> 00:49:17,261 ALPHA GLOBIN MUTATION. 1138 00:49:17,261 --> 00:49:18,896 IN OUR PRETRANSPLANT POPULATION, 1139 00:49:18,896 --> 00:49:23,401 WE HAD THREE SS, TWO SC AND ONE 1140 00:49:23,401 --> 00:49:25,136 S BETA PLUS, TWO THIRDS, ON 1141 00:49:25,136 --> 00:49:26,237 HYDROXYUREA AND OUR POST 1142 00:49:26,237 --> 00:49:28,773 TRANSPLANT GROUP, WE HAD THREE 1143 00:49:28,773 --> 00:49:30,508 MATCHED SIBLING DONORS, TWO 1144 00:49:30,508 --> 00:49:31,976 HAPLOAND ALL DONORS WERE AS 1145 00:49:31,976 --> 00:49:33,511 EXCEPT FOR ONE, WITH THREE 1146 00:49:33,511 --> 00:49:36,914 MIXED -- EXCUSE ME -- THREE FULL 1147 00:49:36,914 --> 00:49:38,516 CHIMERISM AND TWO MIXED 1148 00:49:38,516 --> 00:49:40,284 CHIMERISM. 1149 00:49:40,284 --> 00:49:42,787 SO IN OUR STUDY, WE INCLUDED 20 1150 00:49:42,787 --> 00:49:45,956 ADULTS WHERE WE WERE ABLE TO EX 1151 00:49:45,956 --> 00:49:48,092 VIVO LABEL THE PATIENTS' RED 1152 00:49:48,092 --> 00:49:52,430 CELLS WITH BIOTIN AND REINFUSE 1153 00:49:52,430 --> 00:49:55,166 THE BIOTIN RED BLOOD CELLS BACK 1154 00:49:55,166 --> 00:49:57,468 TO THE PATIENT AND DO PERIPHERAL 1155 00:49:57,468 --> 00:50:01,439 BLOOD SAMPLING UNTIL BIOTIN WAS 1156 00:50:01,439 --> 00:50:04,408 BELOW THE DETECTION LEVEL. 1157 00:50:04,408 --> 00:50:06,477 YOU CAN GET THESE SIMPLE BUT 1158 00:50:06,477 --> 00:50:08,112 ELEGANT FLOW PLOTS WHERE YOU CAN 1159 00:50:08,112 --> 00:50:09,847 SEE IN THE PATIENT PREBIOTIN YOU 1160 00:50:09,847 --> 00:50:11,615 MIGHT HAVE HAD SOME AUTO 1161 00:50:11,615 --> 00:50:12,717 FLUORESCENCE. 1162 00:50:12,717 --> 00:50:15,786 WE HAD IN THE BIOTIN PRODUCT 1163 00:50:15,786 --> 00:50:17,388 100% LABELED WITH BIOTIN, 20 1164 00:50:17,388 --> 00:50:19,356 MINUTES AFTER INFUSION WAS OUR 1165 00:50:19,356 --> 00:50:20,925 FIRST BLOOD SAMPLE WHERE YOU'D 1166 00:50:20,925 --> 00:50:21,892 GET A PROPORTION OF THE BLOOD 1167 00:50:21,892 --> 00:50:23,461 THAT WAS BIOTIN-POSITIVE AND 1168 00:50:23,461 --> 00:50:24,562 THEN YOU COULD TRACK THAT OVER 1169 00:50:24,562 --> 00:50:28,933 TIME. 1170 00:50:28,933 --> 00:50:31,936 SO WE COULD GENERATE THESE 1171 00:50:31,936 --> 00:50:33,537 SURVIVAL CURVES WHICH COULD SHOW 1172 00:50:33,537 --> 00:50:34,972 NORMALIZATION OF RED CELL 1173 00:50:34,972 --> 00:50:36,273 SURVIVAL AFTER TRANSPLANT 1174 00:50:36,273 --> 00:50:38,375 COMPARED TO PATIENTS BEFORE 1175 00:50:38,375 --> 00:50:39,677 TRANSPLANT, AND FOR FIGURE B ON 1176 00:50:39,677 --> 00:50:41,345 THE RIGHT, YOU CAN SEE THE 1177 00:50:41,345 --> 00:50:43,647 DIFFERENCES BETWEEN SS GENOTYPE 1178 00:50:43,647 --> 00:50:46,383 AND SCS BETA PLUS AND THE 1179 00:50:46,383 --> 00:50:47,618 DIFFERENCES BETWEEN FULL AND 1180 00:50:47,618 --> 00:50:49,253 DONOR MYELOID CHIMERISM, WHICH 1181 00:50:49,253 --> 00:50:51,088 BOTH OF THEM SHOW A NORMAL RED 1182 00:50:51,088 --> 00:50:55,025 CELL SURVIVAL CURVE. 1183 00:50:55,025 --> 00:50:57,228 TO GIVE YOU A LITTLE BIT OF 1184 00:50:57,228 --> 00:51:00,097 PERSPECTIVE ON THIS, THESE 1185 00:51:00,097 --> 00:51:03,601 FIGURES, THIS IS HPLC DATA. 1186 00:51:03,601 --> 00:51:05,770 WHAT WE COULD SHOW IS THAT ANY 1187 00:51:05,770 --> 00:51:08,205 TYPE OF NON-HEMOGLOBIN S 1188 00:51:08,205 --> 00:51:09,673 HEMOGLOBIN IS WHAT PROLONGS THE 1189 00:51:09,673 --> 00:51:11,375 RED CELLS IN THE PERIPHERAL 1190 00:51:11,375 --> 00:51:12,910 BLOOD. 1191 00:51:12,910 --> 00:51:15,212 SO FOR THIS COHORT, THIS IS OUR 1192 00:51:15,212 --> 00:51:16,680 PRETRANSPLANT COHORT, IT'S 1193 00:51:16,680 --> 00:51:19,450 EITHER FETAL HEMOGLOBIN OR 1194 00:51:19,450 --> 00:51:22,253 HEMOGLOBIN C THAT IS PERSISTENT 1195 00:51:22,253 --> 00:51:23,154 AT THE VERY END. 1196 00:51:23,154 --> 00:51:26,023 SO TO ORIENT YOU, FOR EXAMPLE, 1197 00:51:26,023 --> 00:51:29,527 FOR THE FIRST FIGURE ON THE TOP 1198 00:51:29,527 --> 00:51:32,830 LEFT, WE DID R RETICULOCYTE 1199 00:51:32,830 --> 00:51:34,899 ISOLATION WITH HPLC, WHICH YOU 1200 00:51:34,899 --> 00:51:36,767 CAN SEE ARE PRIMARILY SICKLE 1201 00:51:36,767 --> 00:51:37,301 GLOBIN. 1202 00:51:37,301 --> 00:51:40,538 WE DID HPLC ON WHOLE BLOOD WHICH 1203 00:51:40,538 --> 00:51:41,839 IS WHAT YOU WOULD MEASURE IN THE 1204 00:51:41,839 --> 00:51:45,342 CLINIC, WE DID HPLC ON THE 1205 00:51:45,342 --> 00:51:47,711 BIOTIN POSITIVE FRACTION AT THE 1206 00:51:47,711 --> 00:51:48,712 BEGINNING AND AT THE VERY END, 1207 00:51:48,712 --> 00:51:51,782 YOU CAN SEE ENRICHMENT FOR HBSS 1208 00:51:51,782 --> 00:51:54,185 IN HBF OVER TIME, AND FOR THE SC 1209 00:51:54,185 --> 00:51:55,219 PATIENTS INTERESTINGLY WE SAW A 1210 00:51:55,219 --> 00:51:57,388 HIGHER FRACTION OF HEMOGLOBIN C 1211 00:51:57,388 --> 00:51:59,590 COMPARED TO HEMOGLOBIN S AT THE 1212 00:51:59,590 --> 00:52:04,428 VERY END OF THE STUDY. 1213 00:52:04,428 --> 00:52:10,334 FOR OUR POST TRANSPLANT COHORT, 1214 00:52:10,334 --> 00:52:12,970 NOT SURPRISINGLY -- COMPLETE 1215 00:52:12,970 --> 00:52:15,239 DONOR A SDOH NORS, WHAT YOU GET 1216 00:52:15,239 --> 00:52:16,574 IN RETICULOCYTE IN THE WHOLE 1217 00:52:16,574 --> 00:52:19,109 BLOOD AND AT THE END OF STUDY IS 1218 00:52:19,109 --> 00:52:20,845 DONOR DERIVED AND STABLE AS 1219 00:52:20,845 --> 00:52:22,880 OPPOSED TO WHAT WE SEE WITH OUR 1220 00:52:22,880 --> 00:52:26,617 TWO MIXED CHIMERISM PATIENTS, 1221 00:52:26,617 --> 00:52:28,052 WHAT YOU SEE IS THAT THE 1222 00:52:28,052 --> 00:52:30,788 RETICULOCYTES ARE PRIMARILY 1223 00:52:30,788 --> 00:52:32,223 RECIPIENT DERIVED AND OVER TIME 1224 00:52:32,223 --> 00:52:33,324 OBVIOUSLY THE RED CELLS THAT ARE 1225 00:52:33,324 --> 00:52:34,758 LASTING THE LONGEST ARE 1226 00:52:34,758 --> 00:52:39,463 CONSISTENT WITH THE DONORS. 1227 00:52:39,463 --> 00:52:40,664 AND THIS WAS CONSISTENT WITH 1228 00:52:40,664 --> 00:52:44,401 WHAT WE SAW IN SINGLE CELL 1229 00:52:44,401 --> 00:52:45,502 WESTERN, SO THE CLOSED CIRCLES 1230 00:52:45,502 --> 00:52:47,905 ARE THE BIOTIN-POSITIVE 1231 00:52:47,905 --> 00:52:48,472 FRACTION. 1232 00:52:48,472 --> 00:52:50,341 IN BLUE IS THE DONOR DERIVED RED 1233 00:52:50,341 --> 00:52:53,711 CELLS THAT ENRICH OVER TIME, AND 1234 00:52:53,711 --> 00:52:56,614 IN RED ARE THE RECIPIENT DERIVED 1235 00:52:56,614 --> 00:53:01,619 THAT ARE MUCH LOWER OVER TIME. 1236 00:53:01,619 --> 00:53:02,820 AND WHEN WE CORRELATED THIS WITH 1237 00:53:02,820 --> 00:53:06,891 THE FINAL FRACTION OF SICKLED 1238 00:53:06,891 --> 00:53:08,759 RED CELLS AFTER DEOXYGENATION, 1239 00:53:08,759 --> 00:53:10,628 WE COULD STRONGLY CORRELATE THIS 1240 00:53:10,628 --> 00:53:11,729 WITH RED CELL LIFESPAN. 1241 00:53:11,729 --> 00:53:14,665 SO IT'S NOT SURPRISING THAT 1242 00:53:14,665 --> 00:53:16,233 PATIENTS' PRETRANSPLANT -- 1243 00:53:16,233 --> 00:53:21,138 HIGHER PERCENTAGE OF RED 1244 00:53:21,138 --> 00:53:22,373 CELLS -- FOR EXAMPLE IN GREEN, 1245 00:53:22,373 --> 00:53:26,410 THE SC PATIENTS. 1246 00:53:26,410 --> 00:53:28,379 WHEN WE BLOT THIS AGAINST THE 1247 00:53:28,379 --> 00:53:30,814 RED CELL SURVIVAL, WE SEE A VERY 1248 00:53:30,814 --> 00:53:31,582 STRONG CORRELATION TO WHAT 1249 00:53:31,582 --> 00:53:33,117 SICKLES TO HOW LONG YOUR RED 1250 00:53:33,117 --> 00:53:35,219 CELLS LAST IN THE PERIPHERAL 1251 00:53:35,219 --> 00:53:38,689 BLOOD. 1252 00:53:38,689 --> 00:53:39,723 AND WHAT'S INTERESTING IS THAT 1253 00:53:39,723 --> 00:53:42,092 YOU CAN SEE THAT AT A CERTAIN 1254 00:53:42,092 --> 00:53:44,194 THRESHOLD, WE SEE PATIENT THAT 1255 00:53:44,194 --> 00:53:50,234 ARE SYMPTOMATIC VERSUS 1256 00:53:50,234 --> 00:53:52,536 ASYMPTOMATIC PATIENTS, SO EVEN 1257 00:53:52,536 --> 00:53:54,171 OUR MIXED CHIMERISM PATIENTS 1258 00:53:54,171 --> 00:53:55,572 WERE ASYMPTOMATIC AT THE TIME, 1259 00:53:55,572 --> 00:53:58,108 AND THAT SC PATIENT 23 WAS A 1260 00:53:58,108 --> 00:54:00,978 PATIENT WITH SC DISEASE THAT HAD 1261 00:54:00,978 --> 00:54:02,279 NO SYMPTOMS, AND SO SOMEWHERE IN 1262 00:54:02,279 --> 00:54:04,715 THERE IS SOME THRESHOLD THAT 1263 00:54:04,715 --> 00:54:06,817 SHOWS US WHERE PATIENTS MIGHT 1264 00:54:06,817 --> 00:54:10,621 REMAIN ASYMPTOMATIC. 1265 00:54:10,621 --> 00:54:12,589 WHEN WE PLOTTED THIS WITH 1266 00:54:12,589 --> 00:54:14,391 HISTORICAL DATA FROM PATIENTS 1267 00:54:14,391 --> 00:54:16,794 THAT WERE TREATED WITH GENE 1268 00:54:16,794 --> 00:54:19,730 THERAPY T87Q GENE ADDITION, WE 1269 00:54:19,730 --> 00:54:21,832 COULD SHOW THAT A FRACTION OF 1270 00:54:21,832 --> 00:54:23,367 SICKLING THAT OCCURS OVER TIME 1271 00:54:23,367 --> 00:54:26,437 IS OBVIOUSLY HIGH IN OUR SS 1272 00:54:26,437 --> 00:54:27,972 PRETRANSPLANT, AND IS STABLE AND 1273 00:54:27,972 --> 00:54:29,740 LOW IN THE PATIENTS THAT HAD 1274 00:54:29,740 --> 00:54:32,042 100% DONOR CHIMERISM, BUT WE 1275 00:54:32,042 --> 00:54:33,711 COULD SEE AN EQUIVALENT FRACTION 1276 00:54:33,711 --> 00:54:35,679 BECAUSE WE COULD SEE SOME 1277 00:54:35,679 --> 00:54:37,648 RETICULOCYTES, FOR EXAMPLE, THAT 1278 00:54:37,648 --> 00:54:39,984 WERE RECIPIENT DERIVED IN THE 1279 00:54:39,984 --> 00:54:40,851 PERIPHERAL BLOOD SIMILAR TO WHAT 1280 00:54:40,851 --> 00:54:43,253 YOU SEE WITH PATIENTS WITH T87Q 1281 00:54:43,253 --> 00:54:44,588 ADDITION BECAUSE WE KNOW IT'S 1282 00:54:44,588 --> 00:54:49,159 NOT 100% REPLACEMENT. 1283 00:54:49,159 --> 00:54:51,228 IN GENERAL THIS WAS SAFE AND 1284 00:54:51,228 --> 00:54:53,964 FEASIBLE, THERE ARE NO ADVERSE 1285 00:54:53,964 --> 00:54:55,733 EVENTS ATTRIBUTABLE TO USING BUY 1286 00:54:55,733 --> 00:54:58,802 TIN, WE HAD NO EMERGENCY ROOM 1287 00:54:58,802 --> 00:55:01,238 VISITS AND NO ANTIBODIES WERE 1288 00:55:01,238 --> 00:55:04,074 DETECT TODAY BIOTIN. 1289 00:55:04,074 --> 00:55:06,276 DETECTED TO PI BUY TIN. 1290 00:55:06,276 --> 00:55:09,013 SO IN SUMMARY, BIOTIN LABEL IS 1291 00:55:09,013 --> 00:55:11,749 SAFE AND FEASIBLE TO EVALUATE 1292 00:55:11,749 --> 00:55:13,617 RED CELL SURVIVAL BEFORE AND 1293 00:55:13,617 --> 00:55:15,185 AFTER TRANSPLANT IN PATIENTS 1294 00:55:15,185 --> 00:55:17,821 WITH SICKLE CELL. 1295 00:55:17,821 --> 00:55:19,156 RBC LIFESPAN STRONGLY CORRELATES 1296 00:55:19,156 --> 00:55:20,557 TO THAT FINAL FRACTION OF 1297 00:55:20,557 --> 00:55:22,659 SICKLED RED CELLS AFTER 1298 00:55:22,659 --> 00:55:23,727 DEOXYGENATION AND SEPARATES 1299 00:55:23,727 --> 00:55:25,162 WHO'S SYMPTOMATIC FROM 1300 00:55:25,162 --> 00:55:26,363 ASYMPTOMATIC. 1301 00:55:26,363 --> 00:55:28,165 THE DIFFERENCES IN RED CELL 1302 00:55:28,165 --> 00:55:30,334 SURVIVAL MAY INFORM THE 1303 00:55:30,334 --> 00:55:30,801 HEMOGLOBIN COMPOSITION 1304 00:55:30,801 --> 00:55:31,869 THRESHOLDS THAT WE NEED TO 1305 00:55:31,869 --> 00:55:34,204 REVERSE THE PHENOTYPE AFTER GENE 1306 00:55:34,204 --> 00:55:37,608 THERAPY, FOR EXAMPLE. 1307 00:55:37,608 --> 00:55:38,909 WOOR USING ONGOING WORK AND HAVE 1308 00:55:38,909 --> 00:55:40,244 A NEW PROTOCOL THAT'S OPEN NOW 1309 00:55:40,244 --> 00:55:42,246 TO STUDY RED CELL SURVIVAL 1310 00:55:42,246 --> 00:55:43,947 BEFORE AND AFTER THINGS LIKE 1311 00:55:43,947 --> 00:55:45,716 DISEASE-MODIFYING THERAPIES AND 1312 00:55:45,716 --> 00:55:49,987 AFTER GENE THERAPY. 1313 00:55:49,987 --> 00:55:51,422 I WANT TO ACKNOWLEDGE ALL OF THE 1314 00:55:51,422 --> 00:55:53,257 STAFF AT THE NIH AND BECAUSE 1315 00:55:53,257 --> 00:55:57,761 THERE IS A NEW OPEN PROTOCOL 1316 00:55:57,761 --> 00:55:59,663 NOW, I INCLUDED CHRISTINA'S 1317 00:55:59,663 --> 00:56:00,964 EMAIL AT THE TOP IF YOU HAVE A 1318 00:56:00,964 --> 00:56:01,932 PATIENT WHO WOULD BE INTERESTING 1319 00:56:01,932 --> 00:56:03,300 TO STUDY THEIR RED CELL 1320 00:56:03,300 --> 00:56:03,600 SURVIVAL. 1321 00:56:03,600 --> 00:56:04,701 AND I THANK YOU ALL FOR YOUR 1322 00:56:04,701 --> 00:56:11,341 TIME AND ATTENTION. 1323 00:56:11,341 --> 00:56:11,608 [APPLAUSE] 1324 00:56:11,608 --> 00:56:15,179 >> THANK YOU, DR. LEONARD. 1325 00:56:15,179 --> 00:56:18,282 QUESTION FROM -- 1326 00:56:18,282 --> 00:56:28,792 >> PLEASE INTRODUCE YOURSELF. 1327 00:56:33,897 --> 00:56:35,232 >> MATT FROM STANFORD. 1328 00:56:35,232 --> 00:56:37,201 VERY NICE TALK. 1329 00:56:37,201 --> 00:56:40,304 SUPER INTERESTING, THE BIOTIN 1330 00:56:40,304 --> 00:56:43,674 LABELING OVER TIME LOOKING AT 1331 00:56:43,674 --> 00:56:45,642 RETICS OVER TIME. 1332 00:56:45,642 --> 00:56:46,877 HOW DOES THAT HELP US UNDERSTAND 1333 00:56:46,877 --> 00:56:49,713 WHEN WE LOOK AT A QUOTE 1334 00:56:49,713 --> 00:56:51,348 HETEROCELLULAR VERSUS 1335 00:56:51,348 --> 00:56:52,816 PANCELLULAR CHIMERISM? 1336 00:56:52,816 --> 00:56:54,218 IT MAY WELL BE THAT WHEN WE TAKE 1337 00:56:54,218 --> 00:56:56,520 A SNAPSHOT, IT APPEARS 1338 00:56:56,520 --> 00:56:58,222 PANCELLULAR BUT WHAT'S REALLY 1339 00:56:58,222 --> 00:56:59,823 HAPPENING IS IT'S A 1340 00:56:59,823 --> 00:57:01,158 HETEROCELLULAR PROCESS THAT 1341 00:57:01,158 --> 00:57:02,259 CONVERTS TO PANCELLULAR. 1342 00:57:02,259 --> 00:57:03,193 AM I THINKING ABOUT THAT THE 1343 00:57:03,193 --> 00:57:03,527 RIGHT WAY? 1344 00:57:03,527 --> 00:57:05,129 >> YEAH, I THINK -- I WAS JUST 1345 00:57:05,129 --> 00:57:06,230 THINKING ABOUT THIS THE OTHER 1346 00:57:06,230 --> 00:57:09,199 DAY, BUT THERE MUST BE -- YOU 1347 00:57:09,199 --> 00:57:10,300 KNOW, IT WAS SOMEWHAT SURPRISING 1348 00:57:10,300 --> 00:57:12,903 TO SEE POSITIVE FRACTION OF 1349 00:57:12,903 --> 00:57:15,572 DONOR -- EXCUSE ME -- RECIPIENT 1350 00:57:15,572 --> 00:57:16,773 RETICS IN THE PERIPHERAL BLOOD, 1351 00:57:16,773 --> 00:57:19,309 SO THERE MUST BE SOME THRESHOLD 1352 00:57:19,309 --> 00:57:22,846 WHERE THE RETICS AND THE ENTIRE 1353 00:57:22,846 --> 00:57:24,915 PERIPHERAL BLOOD IS THE DONOR OR 1354 00:57:24,915 --> 00:57:26,650 WHATEVER FRACTION OF 1355 00:57:26,650 --> 00:57:28,652 ANTISICKLING GLOBIN WAS INCLUDED 1356 00:57:28,652 --> 00:57:30,320 AFTER GENE THERAPY AND HOPEFULLY 1357 00:57:30,320 --> 00:57:33,023 WE'LL BE ABLE TO ELUCIDATE THAT 1358 00:57:33,023 --> 00:57:36,860 IN THIS LARGER STUDY WITH TWO -- 1359 00:57:36,860 --> 00:57:38,996 ONLY TWO MIXED CHIMERISM 1360 00:57:38,996 --> 00:57:40,264 PATIENTS, WE CAN'T QUITE SAY FOR 1361 00:57:40,264 --> 00:57:42,833 SURE WHERE THAT THRESHOLD IS, 1362 00:57:42,833 --> 00:57:48,205 BUT IT'S SOMEWHERE THAT WE CAN 1363 00:57:48,205 --> 00:57:48,772 HOPEFULLY FIGURE OUT BY 1364 00:57:48,772 --> 00:57:49,873 MEASURING THIS IN LARGER 1365 00:57:49,873 --> 00:57:52,309 COHORTS. 1366 00:57:52,309 --> 00:57:56,213 >> GREG FROM CSL AND KIM OF 1367 00:57:56,213 --> 00:57:56,580 PENNSYLVANIA. 1368 00:57:56,580 --> 00:57:59,049 THIS IS REALLY WONDERFUL SCIENCE 1369 00:57:59,049 --> 00:58:02,286 AND USING A GREAT TECHNIQUE FOR 1370 00:58:02,286 --> 00:58:08,525 MEASURING RED CELL SURVIVAL. 1371 00:58:08,525 --> 00:58:10,160 THE BIOTIN LABELING IS REALLY 1372 00:58:10,160 --> 00:58:11,595 EFFECTIVE OVER A WIDE RANGE OF 1373 00:58:11,595 --> 00:58:19,169 RED CELL SURVIVALS BUT I 1374 00:58:19,169 --> 00:58:20,270 WONDERED IF YOU WERE ABLE TO 1375 00:58:20,270 --> 00:58:26,176 CORRELATE SERUM HAPP HAP GLOBIN 1376 00:58:26,176 --> 00:58:29,813 LEVELS TO THE MILDER DEGREES OF 1377 00:58:29,813 --> 00:58:31,014 HEMOLYSIS POST TRANSPLANT. 1378 00:58:31,014 --> 00:58:32,382 >> THAT'S A GREAT POINT AND 1379 00:58:32,382 --> 00:58:33,450 ACTUALLY WE HAVE DISCUSSED THAT. 1380 00:58:33,450 --> 00:58:35,319 IT WASN'T IN THE ORIGINAL 1381 00:58:35,319 --> 00:58:38,488 PROTOCOL FOR US TO OBTAIN IT. 1382 00:58:38,488 --> 00:58:40,157 AND I CAN'T REMEMBER IF WE PUT 1383 00:58:40,157 --> 00:58:41,491 IT IN THE NEW ONE, BUT IF IT'S 1384 00:58:41,491 --> 00:58:43,126 NOT IN THE NEW ONE, WE WILL PUT 1385 00:58:43,126 --> 00:58:45,229 IT IN THERE BECAUSE I AGREE IT 1386 00:58:45,229 --> 00:58:45,996 AN IMPORTANT CORRELATIVE THAT 1387 00:58:45,996 --> 00:58:46,496 WILL HELP US. 1388 00:58:46,496 --> 00:58:46,797 >> GREAT. 1389 00:58:46,797 --> 00:58:49,099 THANK YOU. 1390 00:58:49,099 --> 00:58:50,968 >> THANK YOU, DR. LEONARD. 1391 00:58:50,968 --> 00:58:54,671 WE'RE GOING TO MOVE TO OUR NEXT 1392 00:58:54,671 --> 00:58:57,107 SPEAKER, WHO DR. KRISH WILL 1393 00:58:57,107 --> 00:58:57,374 INTRODUCE. 1394 00:58:57,374 --> 00:58:59,643 >> AS IS EVIDENT FROM THE 1395 00:58:59,643 --> 00:59:03,113 CONVERSATION THIS MORNING, A LOT 1396 00:59:03,113 --> 00:59:04,448 OF THE WORK ON CURATIVE 1397 00:59:04,448 --> 00:59:04,982 THERAPIES FOR SICKLE CELL 1398 00:59:04,982 --> 00:59:06,650 DISEASE IS OCCURRING ALL OVER 1399 00:59:06,650 --> 00:59:09,853 THE WORLD, NOT ONLY THE UNITED 1400 00:59:09,853 --> 00:59:12,055 STATES, AND TO TALK ABOUT ONE OF 1401 00:59:12,055 --> 00:59:14,992 THE CONSORTIA, THE VANDERBILT 1402 00:59:14,992 --> 00:59:16,193 CONSORTIA THAT'S PLAYED AN 1403 00:59:16,193 --> 00:59:18,729 IMPORTANT ROLE IN ADVANCING 1404 00:59:18,729 --> 00:59:20,230 HAPLOIDENTICAL TRANSPLANT, WE 1405 00:59:20,230 --> 00:59:23,934 HAVE DR. ERPHAN NUR. 1406 00:59:23,934 --> 00:59:25,469 DR. NUR WILL BE SPEAKING TO US 1407 00:59:25,469 --> 00:59:28,505 FROM THE AMSTERDAM UNIVERSITY 1408 00:59:28,505 --> 00:59:33,010 MEDICAL CENTER AND SANQUIN 1409 00:59:33,010 --> 00:59:36,513 RESEARCH AND LANDSTEINER 1410 00:59:36,513 --> 00:59:38,282 LABORATORY AMSTERDAM, THE 1411 00:59:38,282 --> 00:59:39,850 NETHERLANDS, AND HE WILL TALK TO 1412 00:59:39,850 --> 00:59:41,818 US ABOUT THE VANDERBILT GLOBAL 1413 00:59:41,818 --> 00:59:42,819 HAPLOIDENTICAL CONSORTIUM 1414 00:59:42,819 --> 00:59:43,687 PART 2, NEXT STEPS FROM 1415 00:59:43,687 --> 00:59:47,090 NASHVILLE TO AMSTERDAM. 1416 00:59:47,090 --> 00:59:47,324 DR. NUR. 1417 00:59:47,324 --> 00:59:49,326 >> THANK YOU VERY MUCH, KRISH. 1418 00:59:49,326 --> 00:59:50,394 THANKS FOR THIS OPPORTUNITY TO 1419 00:59:50,394 --> 00:59:52,062 PRESENT AT THIS GREAT MEETING ON 1420 00:59:52,062 --> 00:59:54,931 BEHALF OF OUR VANDERBILT GLOBAL 1421 00:59:54,931 --> 00:59:56,166 CONSORTIUM. 1422 00:59:56,166 --> 00:59:58,568 YOU EXPLAINED THE TITLE VERY 1423 00:59:58,568 --> 01:00:01,405 WELL. 1424 01:00:01,405 --> 01:00:04,041 SO IT'S SAFE TO SAY THAT 1425 01:00:04,041 --> 01:00:04,741 ALLOGENEIC STEM CELL 1426 01:00:04,741 --> 01:00:05,709 TRANSPLANTATION IS AN 1427 01:00:05,709 --> 01:00:08,211 ESTABLISHED CURATIVE THERAPY FOR 1428 01:00:08,211 --> 01:00:08,745 PATIENTS WITH SICKLE CELL 1429 01:00:08,745 --> 01:00:10,647 DISEASE. 1430 01:00:10,647 --> 01:00:13,283 BUT THERE ARE TWO MAIN 1431 01:00:13,283 --> 01:00:14,217 CHALLENGES PARTICULARLY FOR 1432 01:00:14,217 --> 01:00:16,453 ADULTS WITH SICKLE CELL DISEASE. 1433 01:00:16,453 --> 01:00:18,455 FIRST IS THE SIGNIFICANT 1434 01:00:18,455 --> 01:00:20,624 TOXICITY WHICH BRINGS WITH IT 1435 01:00:20,624 --> 01:00:23,527 MORTALITY WITH MYELOABLATIVE 1436 01:00:23,527 --> 01:00:24,461 CONDITIONING REGIMENS AND SECOND 1437 01:00:24,461 --> 01:00:26,563 IS THE LIMITED POOL OF HLA 1438 01:00:26,563 --> 01:00:31,068 IDENTICAL SIBLING DONORS. 1439 01:00:31,068 --> 01:00:32,636 SICKLE CELL DISEASE ASSOCIATED 1440 01:00:32,636 --> 01:00:34,271 WITH AN ACCELERATED BIOLOGICAL 1441 01:00:34,271 --> 01:00:36,573 AGING OF VITAL ORGANS, INCLUDING 1442 01:00:36,573 --> 01:00:39,009 THE LUNGS, HEART AND KIDNEYINGS, 1443 01:00:39,009 --> 01:00:43,313 AND THIS KIDNEYS,AND THIS IS ASH 1444 01:00:43,313 --> 01:00:46,049 INCREASED MORTALITY IN SICKLE 1445 01:00:46,049 --> 01:00:48,218 CELL DISEASE, AND TOXICITY BY 1446 01:00:48,218 --> 01:00:50,754 THE CONDITIONING REGIMEN 1447 01:00:50,754 --> 01:00:52,122 ESPECIALLY IF IT'S 1448 01:00:52,122 --> 01:00:54,057 MYELOABLATIVE, THESE ORGANS 1449 01:00:54,057 --> 01:00:55,058 MIGHT ALSO CONTRIBUTE TO THE 1450 01:00:55,058 --> 01:00:56,960 INCREASED MORTALITY, ESPECIALLY 1451 01:00:56,960 --> 01:00:58,362 IN ADULTS WITH SICKLE CELL 1452 01:00:58,362 --> 01:00:59,363 DISEASE. 1453 01:00:59,363 --> 01:01:00,797 SO THE SECOND CHALLENGE AS I 1454 01:01:00,797 --> 01:01:08,438 SAID IS THAT OF LACK OF HL 1455 01:01:08,438 --> 01:01:09,473 IDENTICAL DONORS. 1456 01:01:09,473 --> 01:01:11,375 IN THE LAST 10 TO 15 YEARS, 1457 01:01:11,375 --> 01:01:12,976 SEVERAL STUDYS HAVE BEEN 1458 01:01:12,976 --> 01:01:16,313 PERFORMED TO EVALUATE 1459 01:01:16,313 --> 01:01:16,980 HAPLOIDENTICAL STEM CELL 1460 01:01:16,980 --> 01:01:18,382 TRANSPLANTATION IN PATIENTS WITH 1461 01:01:18,382 --> 01:01:19,716 SICKLE CELL DISEASE, WHILE 1462 01:01:19,716 --> 01:01:21,017 PRELIMINARY RESULTS WERE POOR, 1463 01:01:21,017 --> 01:01:24,354 ESPECIALLY WITH HIGH RATES OF -- 1464 01:01:24,354 --> 01:01:27,457 FAILURE, OUTCOMES HAVE IMPROVED 1465 01:01:27,457 --> 01:01:28,625 GRADUALLY ESPECIALLY WITH THE 1466 01:01:28,625 --> 01:01:32,396 NON-MYELOOWE BLAITIVE OR REDUCED 1467 01:01:32,396 --> 01:01:36,099 INTENSITY REGIMENS AS IN VIVO -- 1468 01:01:36,099 --> 01:01:37,401 HOWEVER THESE STUDIES WERE 1469 01:01:37,401 --> 01:01:39,136 SMALL, MOSTLY SINGLE CENTER, AND 1470 01:01:39,136 --> 01:01:41,271 ALSO USING DIFFERENT 1471 01:01:41,271 --> 01:01:47,244 CONDITIONING REGIMENS. 1472 01:01:47,244 --> 01:01:48,545 SO TO IMPROVE ON THESE RESULTS 1473 01:01:48,545 --> 01:01:51,548 BUT ALSO TO FIND MORE DEFINITIVE 1474 01:01:51,548 --> 01:01:54,284 EVIDENCE, OUR VANDERBILT 1475 01:01:54,284 --> 01:01:57,020 CONSORTIUM SET UP A STUDY WHERE 1476 01:01:57,020 --> 01:02:05,162 WE ADDED THIOTEPA 10 MG TO THE 1477 01:02:05,162 --> 01:02:05,962 EXISTING JOHNS HOPKINS PLATFORM 1478 01:02:05,962 --> 01:02:07,130 THAT WAS DEVELOPED FOR 1479 01:02:07,130 --> 01:02:09,566 NON-MALIGNANT DISEASES. 1480 01:02:09,566 --> 01:02:13,637 SO THIS IS OUR SCREENING AND 1481 01:02:13,637 --> 01:02:14,971 INCLUSION FLOW CHART. 1482 01:02:14,971 --> 01:02:16,473 WE HAD AS YOU CAN SEE IN THE 1483 01:02:16,473 --> 01:02:20,210 LOWER PART HAD 70 PATIENTS WHO 1484 01:02:20,210 --> 01:02:22,379 WERE ASSESSABLE, 32 CHILDREN AND 1485 01:02:22,379 --> 01:02:25,282 38 ADULTS. 1486 01:02:25,282 --> 01:02:29,019 WE HAD 62 SUCCESSFUL 1487 01:02:29,019 --> 01:02:30,387 ENGRAFTMENTS, 8 GRAFT FAILURES, 1488 01:02:30,387 --> 01:02:32,088 INTERESTINGLY ALL OF THEM WERE 1489 01:02:32,088 --> 01:02:35,692 IN CHILDREN, AND WE HAVE 5 TRIAL 1490 01:02:35,692 --> 01:02:36,960 DEATHS TO WHICH I WILL COME IN A 1491 01:02:36,960 --> 01:02:39,262 BIT. 1492 01:02:39,262 --> 01:02:43,099 HERE YOU CAN SEE HOUR EVENT-FREE 1493 01:02:43,099 --> 01:02:46,503 SURVIVAL WHICH WAS -- EVENT WAS 1494 01:02:46,503 --> 01:02:48,371 DEFINED AS GRAFT FAILURE OR 1495 01:02:48,371 --> 01:02:49,673 DEATH DUE TO ANY CAUSE. 1496 01:02:49,673 --> 01:02:51,875 AS YOU CAN SEE EVENT FREE 1497 01:02:51,875 --> 01:02:53,343 SURVIVAL WAS EXCELLENT IN ADULTS 1498 01:02:53,343 --> 01:02:54,878 BUT RATHER POOR IN THE PEDIATRIC 1499 01:02:54,878 --> 01:02:56,713 PATIENTS WHICH WAS PRIMARILY DUE 1500 01:02:56,713 --> 01:02:58,615 TO THE HIGH RATE OF GRAFT 1501 01:02:58,615 --> 01:02:59,816 FAILURE. 1502 01:02:59,816 --> 01:03:02,452 FORTUNATELY ALL PATIENTS WITH 1503 01:03:02,452 --> 01:03:04,421 GRAFT FAILURE DID HAVE 1504 01:03:04,421 --> 01:03:05,422 AUTOLOGOUS REGENERATION AND 1505 01:03:05,422 --> 01:03:10,093 SURVIVED. 1506 01:03:10,093 --> 01:03:12,229 AND THAT RESULTED IN THIS VERY 1507 01:03:12,229 --> 01:03:15,832 GOOD SURVIVAL IN BOTH ADULTS AND 1508 01:03:15,832 --> 01:03:18,835 CHILDREN, WHICH WAS AT 2 YEARS 1509 01:03:18,835 --> 01:03:23,006 AROUND 94%. 1510 01:03:23,006 --> 01:03:26,943 HERE YOU CAN SEE THE CELLULAR 1511 01:03:26,943 --> 01:03:28,478 RECOVERY AND CHIMERISM LEVELS. 1512 01:03:28,478 --> 01:03:30,514 FOR THE SAKE OF CLARITY I'M ONLY 1513 01:03:30,514 --> 01:03:32,883 SHOWING MEDIANS AND HAVE LEFT 1514 01:03:32,883 --> 01:03:33,416 OUT RANGES. 1515 01:03:33,416 --> 01:03:35,619 AS YOU CAN SEE IN THE LOWER PART 1516 01:03:35,619 --> 01:03:39,890 OF THE TABLE, WHOLE BLOOD AND 1517 01:03:39,890 --> 01:03:42,025 CD3 CHIMERISM WERE 100% FOR ALL 1518 01:03:42,025 --> 01:03:48,164 ENGRAFTED PATIENTS. 1519 01:03:48,164 --> 01:03:51,101 97% OF ALL ENGRAFTED PATIENTS 1520 01:03:51,101 --> 01:03:52,802 WERE OFF IMMUNOSUPPRESSION AT 1521 01:03:52,802 --> 01:03:53,136 ONE YEAR. 1522 01:03:53,136 --> 01:03:55,171 AS I SAID, WE HAD FIVE DEATHS, 1523 01:03:55,171 --> 01:03:59,743 ALL PRIMARILY DUE TO INFECTIONS. 1524 01:03:59,743 --> 01:04:02,679 ONE-YEAR INCIDENCE OF GRADE 1525 01:04:02,679 --> 01:04:06,249 III-IV ACUTE GVHD IN ADULTS WAS 1526 01:04:06,249 --> 01:04:07,217 7.9%, WHICH WAS SLIGHTLY LOWER 1527 01:04:07,217 --> 01:04:10,387 THAN IN CHILDREN. 1528 01:04:10,387 --> 01:04:11,388 AND TWO YEARS INCIDENCE OF 1529 01:04:11,388 --> 01:04:14,624 MODERATE TO SEVERE CHRONIC GVHD 1530 01:04:14,624 --> 01:04:17,460 WAS ONLY 2.6% IN ADULTS, WHICH 1531 01:04:17,460 --> 01:04:19,095 WAS SIGNIFICANTLY LOWER THAN IN 1532 01:04:19,095 --> 01:04:25,135 CHILDREN. 1533 01:04:25,135 --> 01:04:27,203 SO WE CAN CONCLUDE THAT 1534 01:04:27,203 --> 01:04:28,405 HAPLOIDENTICAL BMT WITH THIGH 1535 01:04:28,405 --> 01:04:34,311 THIOTEPAAND PTCY IS A VIABLE CUE 1536 01:04:34,311 --> 01:04:35,312 THERAPY FOR ADULTS WITH SICKLE 1537 01:04:35,312 --> 01:04:35,645 CELL DISEASE. 1538 01:04:35,645 --> 01:04:37,113 THERE IS NEED FOR MORE 1539 01:04:37,113 --> 01:04:38,548 OPTIMIZATION IN CHILDREN WHICH 1540 01:04:38,548 --> 01:04:39,416 OUR COLLEAGUES FROM THE 1541 01:04:39,416 --> 01:04:40,850 PEDIATRIC -- ARE WORKING ON, BUT 1542 01:04:40,850 --> 01:04:42,652 THIS PROTOCOL IS INCREASINGLY 1543 01:04:42,652 --> 01:04:44,387 BEING PROVIDED AS STANDARD OF 1544 01:04:44,387 --> 01:04:46,222 CARE TO ADULTS WITH SICKLE CELL 1545 01:04:46,222 --> 01:04:48,825 DISEASE. 1546 01:04:48,825 --> 01:04:50,927 SO THAT BRINGS US TO THE NEXT 1547 01:04:50,927 --> 01:04:53,396 QUESTION OF OUR CONSORTIUM, WHAT 1548 01:04:53,396 --> 01:04:58,635 IS THE EFFECT OF TRANSPLANT 1549 01:04:58,635 --> 01:04:59,569 ON -- RELATED HEALTH EFFECTS, 1550 01:04:59,569 --> 01:05:01,972 WHAT WILL BE THE EFFECT OF THE 1551 01:05:01,972 --> 01:05:03,506 TOXICITY OF THE CONDITIONING 1552 01:05:03,506 --> 01:05:04,608 VERSUS IMPROVEMENT OR 1553 01:05:04,608 --> 01:05:05,675 STABILIZATION DUE TO BEING CURED 1554 01:05:05,675 --> 01:05:08,545 FROM SICKLE CELL DISEASE? 1555 01:05:08,545 --> 01:05:13,183 WE RECENTLY DID THIS LARGE 1556 01:05:13,183 --> 01:05:14,684 SYSTEMATIC REVIEW OF THE EVENT 1557 01:05:14,684 --> 01:05:19,122 OF TRANSPLANT ON SCD-RELATED 1558 01:05:19,122 --> 01:05:19,689 ORGAN DYSFUNCTION. 1559 01:05:19,689 --> 01:05:22,192 THERE WERE MANY STUDIES THAT 1560 01:05:22,192 --> 01:05:24,594 HAVE LOOKED INTO THIS, MOSTLY IN 1561 01:05:24,594 --> 01:05:26,496 PEDIATRIC PATIENTS, AND THERE IS 1562 01:05:26,496 --> 01:05:28,231 SOME STABILIZATION OR MAYBE EVEN 1563 01:05:28,231 --> 01:05:33,203 IMPROVEMENT IN SOME ORGANS, BUT 1564 01:05:33,203 --> 01:05:34,304 SYSTEMATICALLY COLLECTED DATA IN 1565 01:05:34,304 --> 01:05:42,078 ADULTS ARE VERY SCARCE, SO THAT 1566 01:05:42,078 --> 01:05:43,947 BRINGS US -- I THINK THAT LEAVES 1567 01:05:43,947 --> 01:05:44,981 US WITH IMPORTANT REMAINING 1568 01:05:44,981 --> 01:05:48,985 QUESTIONS THAT WE WOULD LAKE TOO 1569 01:05:48,985 --> 01:05:50,920 ANSWER IN PART 2 OF THE 1570 01:05:50,920 --> 01:05:51,855 VANDERBILT GLOBAL CONSORTIUM. 1571 01:05:51,855 --> 01:05:56,226 WE WILL HAVE FOUR MAIN AIMS FOR 1572 01:05:56,226 --> 01:05:56,793 THIS. 1573 01:05:56,793 --> 01:05:58,328 THE FIRST AIM WILL BE IN THE 1574 01:05:58,328 --> 01:05:59,663 INTERMEDIATE AND LATE HEALTH 1575 01:05:59,663 --> 01:06:05,035 EFFECTS OF HAPLOBMT ON HEART, 1576 01:06:05,035 --> 01:06:08,004 LUNGS AND KIDNEYS BUT ALSO IN 1577 01:06:08,004 --> 01:06:09,372 MALE/FEMALE RELATED SYSTEM AS 1578 01:06:09,372 --> 01:06:12,842 FIRST SPEAKER TALKED ABOUT, ALSO 1579 01:06:12,842 --> 01:06:15,679 WE WILL ALSO LOOK INTO OTHER 1580 01:06:15,679 --> 01:06:24,487 SCD-RO-RO-RELATED FUNCTIONS BUTO 1581 01:06:24,487 --> 01:06:26,589 CYST AT THE MAICALLY EVALUATE 1582 01:06:26,589 --> 01:06:27,557 HEALTH-RELATED QUALITY OF LIFE. 1583 01:06:27,557 --> 01:06:28,892 AND THEN AS ALL THE DEATHS WERE 1584 01:06:28,892 --> 01:06:31,594 DUE TO INFECTIONS, WE WILL LOOK 1585 01:06:31,594 --> 01:06:33,329 EXTENSIVELY INTO IMMUNE RESPONSE 1586 01:06:33,329 --> 01:06:37,701 KIMMUNERECONSTITUTION, WE WILL W 1587 01:06:37,701 --> 01:06:39,736 THAT PROSPECTIVELY, AND ALSO 1588 01:06:39,736 --> 01:06:42,372 THERE ARE SOME INDICATIONS THAT 1589 01:06:42,372 --> 01:06:44,274 POOR IMMUNE RECONSTITUTION IS 1590 01:06:44,274 --> 01:06:45,608 RELATED TO GRAFT FAILURE SO WE 1591 01:06:45,608 --> 01:06:47,343 WILL ALSO LOOK INTO RELATION 1592 01:06:47,343 --> 01:06:48,378 WITH CHIMERISM. 1593 01:06:48,378 --> 01:06:49,813 THESE ARE OUR END POINTS. 1594 01:06:49,813 --> 01:06:52,982 I WILL KEEP IT SHORT. 1595 01:06:52,982 --> 01:06:56,186 JUST TO THE PRIMARY ENDS POINTS 1596 01:06:56,186 --> 01:07:05,095 OF AIM ONE, WE WILL LOOK AT 1597 01:07:05,095 --> 01:07:09,032 PROM -- THAT WILL INCLUDE GRAFT 1598 01:07:09,032 --> 01:07:12,802 FAILURE, DEATH, BUT ALSO GRADE 1599 01:07:12,802 --> 01:07:15,238 III TO IV AND ALSO CHRONIC TO 1600 01:07:15,238 --> 01:07:18,908 SEVERE, AND WE WILL -- FOR -- WE 1601 01:07:18,908 --> 01:07:22,512 WILL USE PROMIS MEASURE FOR THE 1602 01:07:22,512 --> 01:07:24,481 QUALITY OF LIFE AND PAIN WILL BE 1603 01:07:24,481 --> 01:07:25,849 OUR PRIMARY END POINT. 1604 01:07:25,849 --> 01:07:28,151 AND FOR THE IMMUNE 1605 01:07:28,151 --> 01:07:29,018 RECONSTITUTION, THAT WILL BE 1606 01:07:29,018 --> 01:07:29,452 SITE-SPECIFIC. 1607 01:07:29,452 --> 01:07:32,288 WE WILL COLLECT AND STORE PBMC 1608 01:07:32,288 --> 01:07:34,657 AT SOME CENTERS AND THEN PRIMARY 1609 01:07:34,657 --> 01:07:40,897 INPUT WILL BE AT 3 MONTHS. 1610 01:07:40,897 --> 01:07:43,800 JUST SHORTLY, THIS WILL BE AN 1611 01:07:43,800 --> 01:07:45,201 INTERNATIONAL RETROSPECTIVE ALSO 1612 01:07:45,201 --> 01:07:46,302 PROSPECTIVE STUDY USING OUR 1613 01:07:46,302 --> 01:07:47,270 PROTOCOL IN ADULTS. 1614 01:07:47,270 --> 01:07:51,808 WE WILL SET UP A REDCAP 1615 01:07:51,808 --> 01:07:52,475 DATABASE. 1616 01:07:52,475 --> 01:07:55,745 THE DATA TRANSFER COORDINATING 1617 01:07:55,745 --> 01:07:58,448 CENTER WILL MOVE FROM VANDERBILT 1618 01:07:58,448 --> 01:08:01,818 UMC TO AMSTERDAM UMC, FOR HEALTH 1619 01:08:01,818 --> 01:08:04,487 RELATED OUTCOMES WE WILL USE A 1620 01:08:04,487 --> 01:08:06,222 WEB-BASED PROMIS QUESTIONNAIRE 1621 01:08:06,222 --> 01:08:07,891 AVAILABLE IN DIFFERENT LANGUAGES 1622 01:08:07,891 --> 01:08:09,893 AND FOR PBMC WILL BE SITE 1623 01:08:09,893 --> 01:08:15,799 SPECIFIC, WE WILL DO BIOBANKING. 1624 01:08:15,799 --> 01:08:17,333 WITH THAT, I WOULD LIKE TO THANK 1625 01:08:17,333 --> 01:08:19,669 ALL THE PATIENTS, ALL THE 1626 01:08:19,669 --> 01:08:21,638 CAREGIVERS AND ALL THE PRINCIPAL 1627 01:08:21,638 --> 01:08:22,739 INVESTIGATORS WHO WERE TOO MANY 1628 01:08:22,739 --> 01:08:24,274 TO MENTION. 1629 01:08:24,274 --> 01:08:26,910 I WILL SUMMARIZE THE LIST OF 1630 01:08:26,910 --> 01:08:29,112 CENTERS WHO HAVE PARTICIPATED IN 1631 01:08:29,112 --> 01:08:30,980 PART 1 AND/OR WILL PARTICIPATE 1632 01:08:30,980 --> 01:08:33,983 IN PART 2, AND SOME OF THE 1633 01:08:33,983 --> 01:08:35,285 LEADING PERSONS OF OUR 1634 01:08:35,285 --> 01:08:38,121 CONSORTIUM, YOU CAN SEE IN THIS 1635 01:08:38,121 --> 01:08:43,393 PICTURE. 1636 01:08:43,393 --> 01:08:44,260 THANK YOU VERY MUCH. 1637 01:08:44,260 --> 01:08:47,797 [APPLAUSE] 1638 01:08:47,797 --> 01:08:49,899 >> THANK YOU VERY MUCH, DR. NUR. 1639 01:08:49,899 --> 01:08:51,000 WE HAVE A COUPLE OF QUESTIONS IN 1640 01:08:51,000 --> 01:08:52,502 THE CHAT. 1641 01:08:52,502 --> 01:08:53,436 DR. CHRISTINA PETERS WOULD LAKE 1642 01:08:53,436 --> 01:08:55,405 TO YOU COMMENT ON DONOR 1643 01:08:55,405 --> 01:08:58,074 SELECTION. 1644 01:08:58,074 --> 01:09:05,381 >> SO WE AIM FOR FIRST DEGREE 1645 01:09:05,381 --> 01:09:08,484 FAMILY MEMBERS, SO -- AND 1646 01:09:08,484 --> 01:09:13,289 YOUNGER RATHER THAN OLD EARLY, 1647 01:09:13,289 --> 01:09:15,058 SO IT COULD BE A SIBLING, IT 1648 01:09:15,058 --> 01:09:19,362 COULD BE CHILDREN, BUT IN THE 1649 01:09:19,362 --> 01:09:20,463 CASE OF PARENTS, WHERE MOST OF 1650 01:09:20,463 --> 01:09:23,099 THE DONORS WERE PARENTS, BUT 1651 01:09:23,099 --> 01:09:26,903 THERE WERE ALSO SOME 1652 01:09:26,903 --> 01:09:28,605 SECOND DEGREE FAMILY MEMBERS 1653 01:09:28,605 --> 01:09:31,474 LIKE AUNTS AND UNCLES. 1654 01:09:31,474 --> 01:09:34,310 >> THANK YOU. 1655 01:09:34,310 --> 01:09:35,445 DR. RAHIM HAS AN IMPORTANT 1656 01:09:35,445 --> 01:09:36,379 QUESTION. 1657 01:09:36,379 --> 01:09:37,647 THE HIGHER RATE OF GRAFT 1658 01:09:37,647 --> 01:09:39,849 FAILURE, RIGHT, SO WE'RE USED TO 1659 01:09:39,849 --> 01:09:41,351 CHILDREN DOING BETTER EVERYWHERE 1660 01:09:41,351 --> 01:09:44,420 BUT NOT SO HERE, SO ANY COMMENTS 1661 01:09:44,420 --> 01:09:49,325 ON WHAT MIGHT CONTRIBUTE TO 1662 01:09:49,325 --> 01:09:51,628 HIGHER GRAFT FAILURE IN 1663 01:09:51,628 --> 01:09:51,895 CHILDREN? 1664 01:09:51,895 --> 01:09:53,763 >> I THINK THAT'S THE MILLION 1665 01:09:53,763 --> 01:09:56,132 DOLLAR QUESTION, WHAT'S THE BEST 1666 01:09:56,132 --> 01:10:00,303 OPTIMAL CONDITIONING FOR WHICH 1667 01:10:00,303 --> 01:10:02,805 AGE, SO BY ADDING THIOTEPA, WE 1668 01:10:02,805 --> 01:10:04,307 HOPE THIS WILL WORK FOR ALL 1669 01:10:04,307 --> 01:10:07,243 AGES, BUT IT SEEMS THAT IT'S 1670 01:10:07,243 --> 01:10:11,814 STILL NOT ROBUST ROBUST ENOUGHY 1671 01:10:11,814 --> 01:10:13,116 FOR CHILDREN, WHY CHILDREN TEND 1672 01:10:13,116 --> 01:10:17,954 TO REJEBT M REJECT MORE EASILY O 1673 01:10:17,954 --> 01:10:19,622 NOT WELL-KNOWN, BUT OUR 1674 01:10:19,622 --> 01:10:22,659 COLLEAGUES FROM THE PEDIATRIC 1675 01:10:22,659 --> 01:10:27,864 STRATUM HAVE ALREADY MOVED ON BY 1676 01:10:27,864 --> 01:10:28,898 INTRODUCING A PRECONDITIONING 1677 01:10:28,898 --> 01:10:34,137 WHICH CON SENIOR INVESTIGATOR CF 1678 01:10:34,137 --> 01:10:35,204 HYPERTRANSFUSION EVERY TWO TO 1679 01:10:35,204 --> 01:10:37,373 THREE WEEKS AND KEEPING -- LEVEL 1680 01:10:37,373 --> 01:10:39,776 VERY HIGH, AND ALSO HYDROXYUREA 1681 01:10:39,776 --> 01:10:41,411 AT HIGH LEVELS, WHICH ADULTS 1682 01:10:41,411 --> 01:10:44,113 DON'T REALLY TOLERATE, AND THE 1683 01:10:44,113 --> 01:10:49,385 RESULTS SEEM TO IMPROVE. 1684 01:10:49,385 --> 01:10:54,590 THAT WAS PRESENTED -- THE GRAFT 1685 01:10:54,590 --> 01:10:55,925 FAILURE RATE HAS SIGNIFICANTLY 1686 01:10:55,925 --> 01:10:56,326 DECREASE. 1687 01:10:56,326 --> 01:10:58,628 SO WE WILL SEE HOW THAT DEVELOPS 1688 01:10:58,628 --> 01:11:01,898 WHEN MORE PATIENTS ARE INCLUDED. 1689 01:11:01,898 --> 01:11:06,169 >> DR. RAHIM ALSO WANTS TO KNOW 1690 01:11:06,169 --> 01:11:08,237 WHAT ABOUT PATIENTS THAT DID NOT 1691 01:11:08,237 --> 01:11:09,072 RECEIVE THIOTEPA. 1692 01:11:09,072 --> 01:11:10,473 DID THAT INCLUDE THEM AS WELL, 1693 01:11:10,473 --> 01:11:11,274 THE PEDIATRIC PATIENTS? 1694 01:11:11,274 --> 01:11:13,109 >> NO, IN THIS STUDY ALL 1695 01:11:13,109 --> 01:11:14,610 PATIENTS USED EXACTLY STRICTLY 1696 01:11:14,610 --> 01:11:15,378 THE SAME PROTOCOL. 1697 01:11:15,378 --> 01:11:17,246 THERE WERE THREE PATIENTS WHO 1698 01:11:17,246 --> 01:11:19,115 USED -- WHO HAD SOME VIOLATION 1699 01:11:19,115 --> 01:11:20,016 OF THE PROTOCOL. 1700 01:11:20,016 --> 01:11:21,017 WE EXCLUDED THEM. 1701 01:11:21,017 --> 01:11:22,986 SO ALL PATIENTS IN THIS -- ALL 1702 01:11:22,986 --> 01:11:24,954 THESE 70 PATIENTS DID USE -- DID 1703 01:11:24,954 --> 01:11:25,822 GET THIOTEPA. 1704 01:11:25,822 --> 01:11:28,725 >> THANK YOU, DR. NUR. 1705 01:11:28,725 --> 01:11:29,392 PLEASE ANSWER OTHER QUESTIONS IN 1706 01:11:29,392 --> 01:11:32,395 THE CHAT. 1707 01:11:32,395 --> 01:11:33,296 >> THANKS, I WILL. 1708 01:11:33,296 --> 01:11:35,498 >> SO WE'LL MOVE TO OUR NEXT 1709 01:11:35,498 --> 01:11:39,235 SPEAKER, DR. SHALINI SHENOY FROM 1710 01:11:39,235 --> 01:11:40,136 WASHINGTON UNIVERSITY SCHOOL OF 1711 01:11:40,136 --> 01:11:41,671 MEDICINE WILL BE PRESENTING 1712 01:11:41,671 --> 01:11:44,507 LONG-TERM OUTCOME DATA FROM THE 1713 01:11:44,507 --> 01:11:52,015 BMT CTN 0601 FOR SEVERE SICKLE 1714 01:11:52,015 --> 01:11:52,448 CELL DISEASE TRIAL. 1715 01:11:52,448 --> 01:11:53,716 >> THANK YOU FOR THE INVITATION 1716 01:11:53,716 --> 01:11:54,317 TO PRESENT. 1717 01:11:54,317 --> 01:11:57,220 GOOD MORNING. 1718 01:11:57,220 --> 01:11:59,989 I AM PRESENTING THE OUTCOMES OF 1719 01:11:59,989 --> 01:12:01,624 A TRIAL THAT HAPPENED SOME YEARS 1720 01:12:01,624 --> 01:12:06,662 AGO. 1721 01:12:06,662 --> 01:12:10,566 THE BMT CTN 0601 WAS A TRIAL OF 1722 01:12:10,566 --> 01:12:12,001 UNMATCHED DONOR TRANSPLANTS IN 1723 01:12:12,001 --> 01:12:13,169 CHILDREN WITH SEVERE SICKLE CELL 1724 01:12:13,169 --> 01:12:13,403 DISEASE. 1725 01:12:13,403 --> 01:12:16,305 IT WAS CONDUCTED BETWEEN 2008 1726 01:12:16,305 --> 01:12:18,174 AND 2014. 1727 01:12:18,174 --> 01:12:20,777 IT ENROLLED 30 PATIENTS, THE AGE 1728 01:12:20,777 --> 01:12:25,648 RANGE WAS 3 TO 19.75 YEARS. 1729 01:12:25,648 --> 01:12:29,285 THE SCD MANIFESTATIONS THAT WERE 1730 01:12:29,285 --> 01:12:31,087 ELIGIBLE WERE VASO-OCCLUSION, 1731 01:12:31,087 --> 01:12:36,559 ACUTE CHEST SYNDROME, A HIGH 1732 01:12:36,559 --> 01:12:37,660 TRANSCRANIAL VELOCITY AND STROKE 1733 01:12:37,660 --> 01:12:40,863 AND IT UTILIZED REDUCED 1734 01:12:40,863 --> 01:12:44,367 INTENSITY CONDITIONING INCLUDING 1735 01:12:44,367 --> 01:12:48,104 PROXIMAL/EARLY AL EMTEUZ MAN, 1736 01:12:48,104 --> 01:12:53,843 FLUDARABINE AND MELPHALAN. 1737 01:12:53,843 --> 01:12:55,945 PREDNISONE WAS GIVEN ONE MONTH 1738 01:12:55,945 --> 01:12:58,781 BEFORE THEY CAME FOR THE 1739 01:12:58,781 --> 01:13:00,850 CONDITIONING. 1740 01:13:00,850 --> 01:13:03,386 SHORT COURSE METHOTREXATE WAS IN 1741 01:13:03,386 --> 01:13:05,488 THREE DOSES AND MED ZONE WAS 1742 01:13:05,488 --> 01:13:07,990 ADMINISTERED FOR A MONTH TO 1743 01:13:07,990 --> 01:13:08,891 AVOID THE INFLAMMATORY CHANGES 1744 01:13:08,891 --> 01:13:11,227 THAT HAPPENED PERITRANSPLANT AS 1745 01:13:11,227 --> 01:13:13,763 WELL AS PROVIDE GBHD 1746 01:13:13,763 --> 01:13:14,230 PROPHYLAXIS. 1747 01:13:14,230 --> 01:13:16,766 IT WAS BASED ON A MATCHED 1748 01:13:16,766 --> 01:13:19,402 SIBLING DONOR TRIAL THAT WAS 1749 01:13:19,402 --> 01:13:21,471 PUBLISHED PREVIOUSLY. 1750 01:13:21,471 --> 01:13:23,506 AND IN 43 PATIENTS WITH SICKLE 1751 01:13:23,506 --> 01:13:27,443 CELL DISEASE, THE GRAFT 1752 01:13:27,443 --> 01:13:30,046 REJECTION RATE WAS 2% HERE AND 1753 01:13:30,046 --> 01:13:31,781 5% AND THEY HAD 93% SURVIVAL. 1754 01:13:31,781 --> 01:13:34,417 IN THE MATCHED UNRELATED DONOR, 1755 01:13:34,417 --> 01:13:36,252 WHICH WAS PREVIOUSLY PUBLISHED, 1756 01:13:36,252 --> 01:13:38,287 THE GRAPH ON THE RIGHT PANEL 1757 01:13:38,287 --> 01:13:41,157 SHOWS YOU THE EVENT-FREE 1758 01:13:41,157 --> 01:13:43,226 SURVIVAL AT ONE YEAR WAS 76%, 1759 01:13:43,226 --> 01:13:45,261 THE OVERALL SURVIVAL WAS 86%, 1760 01:13:45,261 --> 01:13:48,531 AND I WILL SHOW YOU THE 1761 01:13:48,531 --> 01:13:54,103 LONGER-TERM FOLLOW-UP DATA. 1762 01:13:54,103 --> 01:13:56,806 THE LESSONS THAT WE LEARNED. 1763 01:13:56,806 --> 01:13:59,575 THE TOP PANEL THERE WAS LOOKING 1764 01:13:59,575 --> 01:14:02,612 AT QUALITY OF LIFE AT ONE YEAR. 1765 01:14:02,612 --> 01:14:05,715 AND IT SHOWED THAT THE GENERAL 1766 01:14:05,715 --> 01:14:08,151 CHANGE IN HEALTH IMPROVED WITH 1767 01:14:08,151 --> 01:14:10,853 TIME, SO IT WAS LOOKED AT AT DAY 1768 01:14:10,853 --> 01:14:12,054 100, SIX MONTHS AND ONE YEAR, 1769 01:14:12,054 --> 01:14:14,557 AND WAS SIGNIFICANTLY DIFFERENT 1770 01:14:14,557 --> 01:14:15,992 OR BETTER AT ONE YEAR THAN IT 1771 01:14:15,992 --> 01:14:18,461 WAS EARLIER, POST TRANSPLANT. 1772 01:14:18,461 --> 01:14:21,197 THE GRAFT REJECTION RATE WAS 1773 01:14:21,197 --> 01:14:22,064 10%. 1774 01:14:22,064 --> 01:14:24,167 ENGRAFTED PATIENTS HAD NO 1775 01:14:24,167 --> 01:14:24,800 FURTHER SICKLE CELL DISEASE 1776 01:14:24,800 --> 01:14:25,334 COMPLICATIONS. 1777 01:14:25,334 --> 01:14:26,869 WITH A TWO-YEAR FOLLOW-UP THAT 1778 01:14:26,869 --> 01:14:29,572 WAS INCLUDED AS PART OF THE 1779 01:14:29,572 --> 01:14:30,339 STUDY. 1780 01:14:30,339 --> 01:14:32,475 THE PRESS RATE WAS 35% AND WAS 1781 01:14:32,475 --> 01:14:34,644 RELATED TO HYPERTENSION AND THE 1782 01:14:34,644 --> 01:14:37,280 STEROIDS THAT WERE USED. 1783 01:14:37,280 --> 01:14:40,349 THE EXTENSIVE CHRONIC GVHD RATE 1784 01:14:40,349 --> 01:14:41,817 WAS THE ONE THAT STOOD OUT THE 1785 01:14:41,817 --> 01:14:43,953 MOST, IT WAS 38% AND 6 PATIENTS 1786 01:14:43,953 --> 01:14:45,821 DIED OF GVHD RELATED 1787 01:14:45,821 --> 01:14:46,155 COMPLICATIONS. 1788 01:14:46,155 --> 01:14:47,990 THEY WERE ALL OVER 14 YEARS OF 1789 01:14:47,990 --> 01:14:48,658 AGE. 1790 01:14:48,658 --> 01:14:51,027 AND THAT DESCRIPTION IS INCLUDED 1791 01:14:51,027 --> 01:14:52,461 IN THE LONGER TERM FOLLOW-UP AS 1792 01:14:52,461 --> 01:15:00,570 WELL. 1793 01:15:00,570 --> 01:15:05,208 NEUROLOGIC FOLLOW-UP AFTER -- I 1794 01:15:05,208 --> 01:15:06,309 WANTED TO TALK BRIEFLY ABOUT 1795 01:15:06,309 --> 01:15:06,509 THAT. 1796 01:15:06,509 --> 01:15:09,412 THE NATURAL HISTORY OF SICKLE 1797 01:15:09,412 --> 01:15:11,314 CELL DISEASE HAS BEEN LOOKED AT 1798 01:15:11,314 --> 01:15:14,217 BY DR. KING FROM MY CENTER, AND 1799 01:15:14,217 --> 01:15:15,585 IT PREDICTS FOR A PROGRESSIVE 1800 01:15:15,585 --> 01:15:18,854 LOSS OF IQ AT ABOUT ONE POINT 1801 01:15:18,854 --> 01:15:20,356 PER YEAR. 1802 01:15:20,356 --> 01:15:22,425 ATTRIBUTABLE TO DISEASE-RELATED 1803 01:15:22,425 --> 01:15:23,593 VASCULOPATHY AND ENSUING THAT 1804 01:15:23,593 --> 01:15:25,928 POLG. 1805 01:15:25,928 --> 01:15:26,362 PATHOLOGY. 1806 01:15:26,362 --> 01:15:29,565 THE NEUROLOGIC OUTCOMES IN 1807 01:15:29,565 --> 01:15:31,234 0601 WAS DETERMINED IN 13 1808 01:15:31,234 --> 01:15:32,101 PATIENTS TREATED ON THE STUDY. 1809 01:15:32,101 --> 01:15:39,809 THE PROTOCOL DIRECTED -- IMAGING 1810 01:15:39,809 --> 01:15:41,711 BY MRI IN 11 PATIENTS AND THE 1811 01:15:41,711 --> 01:15:43,179 PROTOCOL DIRECTED NEUROCOGNITIVE 1812 01:15:43,179 --> 01:15:49,919 FUNCTION INCLUDED THE WECHSLER 1813 01:15:49,919 --> 01:15:51,554 PRESCHOOL AND PRIMARY SCALE OF 1814 01:15:51,554 --> 01:15:55,124 INTELLIGENCE AND THE WECHSLER 1815 01:15:55,124 --> 01:15:59,061 ABBREVIATE PRIMARY SCALE OF 1816 01:15:59,061 --> 01:16:00,396 INTELLIGENCE. 1817 01:16:00,396 --> 01:16:01,530 THAT WAS IN 13 PATIENTS. 1818 01:16:01,530 --> 01:16:04,166 FOR THE NEUROIMAGING STUDY, THE 1819 01:16:04,166 --> 01:16:06,569 AGE -- MEDIAN AGE WAS 12.5 1820 01:16:06,569 --> 01:16:07,003 YEARS. 1821 01:16:07,003 --> 01:16:09,472 SEVEN PATIENTS WERE TRANSPLANTED 1822 01:16:09,472 --> 01:16:12,541 AFTER OVERT STROKE AND ONE HAD 1823 01:16:12,541 --> 01:16:14,443 ELEVATED TCD VELOCITY. 1824 01:16:14,443 --> 01:16:16,679 SIX HAD STABLE MRIs, TWO HAD 1825 01:16:16,679 --> 01:16:18,080 MRI LESION RESOLUTION. 1826 01:16:18,080 --> 01:16:19,849 TWO OF THE EIGHT PATIENTS ARE 1827 01:16:19,849 --> 01:16:21,684 PRES AND THREE PATIENTS HAD NEW 1828 01:16:21,684 --> 01:16:22,118 INFARCTS. 1829 01:16:22,118 --> 01:16:24,053 TWO HAD STABLE IQs AND ONE HAD 1830 01:16:24,053 --> 01:16:31,627 A 10-POINT DROP IN THE IQ. 1831 01:16:31,627 --> 01:16:35,097 THE NEUROCOGNITION ASSESSMENT 1832 01:16:35,097 --> 01:16:36,332 SHOWED I THINK THE TABLE ON THE 1833 01:16:36,332 --> 01:16:38,167 RIGHT SIDE IS EASIER TO FOLLOW. 1834 01:16:38,167 --> 01:16:40,202 THIS IS THE MEDIAN FULL SCALE 1835 01:16:40,202 --> 01:16:42,038 IQ, THE PERFORMANCE IQ AND THE 1836 01:16:42,038 --> 01:16:45,875 VARIABLE IQ. 1837 01:16:45,875 --> 01:16:47,543 THE PRE AND POST TRANSPLANT AT 1838 01:16:47,543 --> 01:16:50,112 TWO YEARS, THE COMPARISON IS 1839 01:16:50,112 --> 01:16:52,214 SHOWN HERE IN NUMBERS. 1840 01:16:52,214 --> 01:16:53,949 AND DIDN'T LOOK MUCH DIFFERENT 1841 01:16:53,949 --> 01:17:00,256 PRE AND POST TRANSPLANT. 1842 01:17:00,256 --> 01:17:02,825 IN THE LONG-TERM FOLLOW-UP, THAT 1843 01:17:02,825 --> 01:17:04,827 WAS MORE RECENTLY LOOKED AT, 20 1844 01:17:04,827 --> 01:17:07,596 PATIENTS WERE TRACKED VAI A THE 1845 01:17:07,596 --> 01:17:09,999 CIBMTR DATA COLLECTION LONG TERM 1846 01:17:09,999 --> 01:17:12,101 FORMS. 1847 01:17:12,101 --> 01:17:14,337 THE MEDIAN AGE AT TRANSPLANT WAS 1848 01:17:14,337 --> 01:17:16,839 13, AND THE MEDIAN AGE AT THE 1849 01:17:16,839 --> 01:17:18,474 TIME POINT THAT WE LOOKED AT NOW 1850 01:17:18,474 --> 01:17:20,009 WAS AT 21. 1851 01:17:20,009 --> 01:17:22,912 AND THE RANGE WAS 11 TO 25 YEARS 1852 01:17:22,912 --> 01:17:26,749 AT THE CURRENT TIME. 1853 01:17:26,749 --> 01:17:29,485 THEY HAD NO LATE SCD RELATED 1854 01:17:29,485 --> 01:17:31,754 EERVETS, NO LATE CNS, CARDIAC, 1855 01:17:31,754 --> 01:17:33,723 HEPATIC, PULMONARY OR RENAL 1856 01:17:33,723 --> 01:17:35,091 COMPLICATIONS THAT WERE REPORTED 1857 01:17:35,091 --> 01:17:38,027 ON THE CIBMTR FORMS, AND IMMUNE 1858 01:17:38,027 --> 01:17:39,362 RECONS FUSION AS WAS COLLECTED 1859 01:17:39,362 --> 01:17:40,429 ON THE FORMS SEEMED TO HAVE 1860 01:17:40,429 --> 01:17:42,832 RECOVERED. 1861 01:17:42,832 --> 01:17:45,901 NOW, 86% HAD OVER FIVE YEARS OF 1862 01:17:45,901 --> 01:17:47,069 FOLLOW-UP AND THE PERFORMANCE 1863 01:17:47,069 --> 01:17:49,905 SCORE IN THOSE PATIENTS IN 13 1864 01:17:49,905 --> 01:17:52,208 WAS 92100 AND 70 TO 80 IN SIX OF 1865 01:17:52,208 --> 01:17:53,409 THE PATIENTS. 1866 01:17:53,409 --> 01:17:55,244 THERE WAS ONE LATE GRAFT 1867 01:17:55,244 --> 01:17:56,545 REJECTION, CHANGING THE GRAFT 1868 01:17:56,545 --> 01:17:58,981 REJECTION RATE TO 14%. 1869 01:17:58,981 --> 01:18:00,483 THERE WERE THREE DEATHS THAT 1870 01:18:00,483 --> 01:18:01,450 HAPPENED BEYOND TWO YEARS. 1871 01:18:01,450 --> 01:18:04,954 SOME OF THESE WERE REPORTED IN 1872 01:18:04,954 --> 01:18:07,356 THE INITIAL PAPER AS WELL. 1873 01:18:07,356 --> 01:18:09,725 TWO WERE DUE TO GVHD 1874 01:18:09,725 --> 01:18:10,593 COMPLICATIONS AND AGAIN BOTH 1875 01:18:10,593 --> 01:18:12,128 PATIENTS WERE OVER 14 YEARS OF 1876 01:18:12,128 --> 01:18:14,964 AGE, AND ONE WAS FOLLOWING A 1877 01:18:14,964 --> 01:18:16,198 SECOND MYELOABLATIVE TRANSPLANT 1878 01:18:16,198 --> 01:18:18,868 AFTER GRAFT REJECTION. 1879 01:18:18,868 --> 01:18:20,002 FIVE PATIENTS IMPORTANTLY WERE 1880 01:18:20,002 --> 01:18:22,138 LOST TO FOLLOW-UP POST 1881 01:18:22,138 --> 01:18:22,471 TRANSPLANT. 1882 01:18:22,471 --> 01:18:24,507 FOUR TO SIX YEARS POST 1883 01:18:24,507 --> 01:18:25,708 TRANSPLANT, AND I WANT TO 1884 01:18:25,708 --> 01:18:27,977 HIGHLIGHT THAT AS A CHALLENGE TO 1885 01:18:27,977 --> 01:18:32,548 LONGER-TERM FOLLOW-UP WHICH WE 1886 01:18:32,548 --> 01:18:33,883 ARE TRYING TO BE MORE CAREFUL 1887 01:18:33,883 --> 01:18:39,455 ABOUT. 1888 01:18:39,455 --> 01:18:41,624 SO THE SURVIVAL RATES AT FIVE 1889 01:18:41,624 --> 01:18:43,359 YEARS AND EIGHT YEARS ARE SHOWN 1890 01:18:43,359 --> 01:18:44,126 HERE. 1891 01:18:44,126 --> 01:18:46,095 THE OVERALL SURVIVAL THEN WAS 1892 01:18:46,095 --> 01:18:48,731 68% AND THE FIVE-YEAR AND 1893 01:18:48,731 --> 01:18:50,733 EIGHT-YEAR EVENT-FREE SURVIVAL 1894 01:18:50,733 --> 01:18:54,236 WAS 61 AND 57%. 1895 01:18:54,236 --> 01:18:56,639 AND THEN THE EFFECTS THAT WERE 1896 01:18:56,639 --> 01:19:02,278 SEEN, GO GONADAL DYSFUNCTION WAS 1897 01:19:02,278 --> 01:19:03,612 FOUR, NO PREGNANCIES REPORTED 1898 01:19:03,612 --> 01:19:05,014 YET BUT GIVEN THAT THE MEDIAN 1899 01:19:05,014 --> 01:19:06,782 AGE IS 21, IT'S HARD TO COMMENT 1900 01:19:06,782 --> 01:19:08,083 ON THAT. 1901 01:19:08,083 --> 01:19:11,220 AVASCULAR NECROSIS IS BEING 1902 01:19:11,220 --> 01:19:13,088 REPORTED IN FOUR PATIENTS, 1903 01:19:13,088 --> 01:19:15,224 PANCREATITIS IN TWO, ADRENAL 1904 01:19:15,224 --> 01:19:17,092 INSUFFICIENCY IN ONE, AND 1905 01:19:17,092 --> 01:19:22,131 DEPRESSION IN 2 PATIENTS. 1906 01:19:22,131 --> 01:19:25,267 OUTSIDE OF THE STUDY, LATE 1907 01:19:25,267 --> 01:19:26,569 HYPOTHYROIDISM HAS BEEN 1908 01:19:26,569 --> 01:19:30,439 DESCRIBED POST ALEMTU SEU. UMAB, 1909 01:19:30,439 --> 01:19:31,907 NO MALIGNANT TRANSFORMATION TO 1910 01:19:31,907 --> 01:19:33,075 DATE IN PATIENTS WITH MIXED 1911 01:19:33,075 --> 01:19:35,811 CHIMERISM OR GRAFT REJECTION. 1912 01:19:35,811 --> 01:19:39,748 SO IN SUMMARY, THE TRANSPLANT 1913 01:19:39,748 --> 01:19:40,816 CURTAILED SICKLE CELL 1914 01:19:40,816 --> 01:19:41,784 MANIFESTATIONS AS WELL AS 1915 01:19:41,784 --> 01:19:43,986 NEUROIMAGING AND NEUROCOGNITIVE 1916 01:19:43,986 --> 01:19:46,856 FUNCTION STABILIZED LATE 1917 01:19:46,856 --> 01:19:48,224 COMPLICATIONS WHEREAS I 1918 01:19:48,224 --> 01:19:50,960 DESCRIBED, BUT THE GVHD 1919 01:19:50,960 --> 01:19:52,261 PROPHYLAXIS IN THESE PATIENTS 1920 01:19:52,261 --> 01:19:54,663 WAS DEFINITELY INADEQUATE, 1921 01:19:54,663 --> 01:19:55,531 ESPECIALLY IN THE PATIENTS THAT 1922 01:19:55,531 --> 01:20:02,638 WERE TEENAGE AND OLDER. 1923 01:20:02,638 --> 01:20:06,842 AND THE PRES RISK WAS HIGH IN 1924 01:20:06,842 --> 01:20:08,511 RELATION TO THE GVHD, TAKING IT 1925 01:20:08,511 --> 01:20:09,812 DOWN TO THE HYPERTENSION AND 1926 01:20:09,812 --> 01:20:11,247 STEROIDS WHICH WERE POORLY 1927 01:20:11,247 --> 01:20:12,181 TOLERATED IN THIS POPULATION. 1928 01:20:12,181 --> 01:20:17,319 WE HAVE GONE ON TO CHANGE THE 1929 01:20:17,319 --> 01:20:18,754 GVHD PROPHYLAXIS THAT'S BEING 1930 01:20:18,754 --> 01:20:20,456 USED GIVEN THE NEWER AGENTS THAT 1931 01:20:20,456 --> 01:20:23,425 ARE NOW AVAILABLE, AND THESE 1932 01:20:23,425 --> 01:20:24,860 PATIENTS FOR UNRELATED AS WELL 1933 01:20:24,860 --> 01:20:26,695 AS MISMATCHED UNRELATED DONOR 1934 01:20:26,695 --> 01:20:29,732 TRANSPLANTS GET EXTENDED 1935 01:20:29,732 --> 01:20:32,034 DURATION ABATACEPT. 1936 01:20:32,034 --> 01:20:33,903 THE FIRST PANEL SHOWS OVERALL 1937 01:20:33,903 --> 01:20:35,938 DISEASE-FREE SURVIVAL AFTER 1938 01:20:35,938 --> 01:20:38,841 ADMINISTRATION OF ABATACEPT IN 1939 01:20:38,841 --> 01:20:42,278 14 PATIENTS AND THE SECOND PANEL 1940 01:20:42,278 --> 01:20:49,451 SHOWS THE SURVIVAL WITHOUT 1941 01:20:49,451 --> 01:20:53,389 ABATACEPT IN A MULTICENTER 1942 01:20:53,389 --> 01:20:58,861 FASHION. 1943 01:20:58,861 --> 01:21:00,996 28% -- AND CHRONIC GVHD 1944 01:21:00,996 --> 01:21:03,098 LOCALIZED OR MILD IS 36%, 1945 01:21:03,098 --> 01:21:06,035 MODERATE TO SEVERE CHRONIC GVHD 1946 01:21:06,035 --> 01:21:09,438 WAS 14% IN THIS POPULATION. 1947 01:21:09,438 --> 01:21:11,340 AND THE PRESS INCIDENCE IS DOWN 1948 01:21:11,340 --> 01:21:12,808 TO 7%. 1949 01:21:12,808 --> 01:21:14,810 IN THIS EARLY LOOK AT 1950 01:21:14,810 --> 01:21:17,012 THESE PATIENTS. 1951 01:21:17,012 --> 01:21:23,352 FOLLOW-UP WAS 1.5 YEARS. 1952 01:21:23,352 --> 01:21:25,454 THAT'S THE LAST OF MY DATA 1953 01:21:25,454 --> 01:21:25,721 SLIDES. 1954 01:21:25,721 --> 01:21:28,824 I WANT TO THANK THE CTN AND THE 1955 01:21:28,824 --> 01:21:30,426 FUNDING SOURCES THAT SUPPORTED 1956 01:21:30,426 --> 01:21:35,798 THIS STUDY. 1957 01:21:35,798 --> 01:21:37,299 THEN THE FOLLOW-UP WE WERE ABLE 1958 01:21:37,299 --> 01:21:38,734 TO DO AFTER, AS WELL AS ALL THE 1959 01:21:38,734 --> 01:21:40,135 PATIENTS AND ALL THE CENTERS 1960 01:21:40,135 --> 01:21:43,105 THAT PARTICIPATED, A LOT OF 1961 01:21:43,105 --> 01:21:43,639 THANKS DUE TO THEM. 1962 01:21:43,639 --> 01:21:46,275 THANK YOU. 1963 01:21:46,275 --> 01:21:49,078 [APPLAUSE] 1964 01:21:49,078 --> 01:21:52,114 >> THANK YOU, DR. SHENOY. 1965 01:21:52,114 --> 01:21:53,349 THERE'S ONE QUESTION IN THE 1966 01:21:53,349 --> 01:21:53,549 CHAT. 1967 01:21:53,549 --> 01:21:56,051 YOTHANK YOU FOR THE IMPORTANT LE 1968 01:21:56,051 --> 01:21:56,485 FOLLOW UP. 1969 01:21:56,485 --> 01:21:57,920 WHAT ARE YOUR STEM CELL SOURCES 1970 01:21:57,920 --> 01:21:59,021 IN THE CURRENT STUDY? 1971 01:21:59,021 --> 01:22:02,658 >> SO WE CURRENTLY USE BONE 1972 01:22:02,658 --> 01:22:03,459 MARROW. 1973 01:22:03,459 --> 01:22:06,595 THERE IS A STRATUM FOR CORD, BUT 1974 01:22:06,595 --> 01:22:10,399 IF IT'S PERIPHERAL BLOOD, WE ARE 1975 01:22:10,399 --> 01:22:13,268 DOING CD34 SELECTION WITH A 1976 01:22:13,268 --> 01:22:13,802 T-CELL ADD BACK. 1977 01:22:13,802 --> 01:22:16,105 WE'RE NOT GIVING THE WHOLE 1978 01:22:16,105 --> 01:22:19,975 PERIPHERAL BLOOD STEM CELLS AS 1979 01:22:19,975 --> 01:22:20,576 AN INFUSION. 1980 01:22:20,576 --> 01:22:24,680 THE MAJORITY OF PATIENTS ARE 1981 01:22:24,680 --> 01:22:26,382 BONE MARROW AND THERE ARE FEW 1982 01:22:26,382 --> 01:22:28,283 PATIENTS THAT GOT CD34 SELECTED 1983 01:22:28,283 --> 01:22:31,920 STEM CELLS. 1984 01:22:31,920 --> 01:22:34,023 THE T CELLS THAT WE ADD ARE 1985 01:22:34,023 --> 01:22:36,859 1 TIMES 10 TO THE 6TH PER KILO 1986 01:22:36,859 --> 01:22:37,726 OF CD3s. 1987 01:22:37,726 --> 01:22:39,895 >> THANK YOU, DR. SHENOY. 1988 01:22:39,895 --> 01:22:41,630 I THINK WE'LL MOVE ON TO OUR 1989 01:22:41,630 --> 01:22:45,434 NEXT SPEAKER. 1990 01:22:45,434 --> 01:22:46,535 PRESENTING ON NEUROLOGIC 1991 01:22:46,535 --> 01:22:51,240 COMPLICATIONS. 1992 01:22:51,240 --> 01:22:54,209 >> TO CONTINUE ON THE THEME OF 1993 01:22:54,209 --> 01:22:55,277 THE EFFECT OF TRANSPLANT ON THE 1994 01:22:55,277 --> 01:22:59,815 BRAIN, WE'LL NOW HEAR ABOUT 1995 01:22:59,815 --> 01:23:01,817 CEREBRAL HEMODYNAMIC CHANGES 1996 01:23:01,817 --> 01:23:02,584 AFTER HAPLOIDENTICAL TRANSPLANT 1997 01:23:02,584 --> 01:23:03,419 IN ADULTS WITH SICKLE CELL 1998 01:23:03,419 --> 01:23:04,286 DISEASE AND TO TALK TO US ABOUT 1999 01:23:04,286 --> 01:23:06,789 THAT IS DR. MEGAN AUMANN FROM 2000 01:23:06,789 --> 01:23:08,424 THE VANDERBILT UNIVERSITY 2001 01:23:08,424 --> 01:23:18,600 MEDICAL CENTER. 2002 01:23:18,600 --> 01:23:20,035 >> THANKS FOR THAT INTRODUCTION. 2003 01:23:20,035 --> 01:23:21,203 I APPRECIATE THE OPPORTUNITY TO 2004 01:23:21,203 --> 01:23:24,273 SPEAK HERE. 2005 01:23:24,273 --> 01:23:26,008 AND WE'LL GO AHEAD AND GET 2006 01:23:26,008 --> 01:23:26,208 GOING. 2007 01:23:26,208 --> 01:23:28,677 WE'RE TALKING ABOUT CEREBRAL 2008 01:23:28,677 --> 01:23:31,580 HEMODYNAMIC CHANGES AFTER 2009 01:23:31,580 --> 01:23:32,247 HAPLOIDENTICAL HEMATOPOIETIC 2010 01:23:32,247 --> 01:23:35,184 STEM CELL TRANSPLANT IN ADULTS. 2011 01:23:35,184 --> 01:23:38,687 SO EVERYONE IS FAMILIAR WITH 2012 01:23:38,687 --> 01:23:39,321 SICKLE CELL DISEASE, AND THE WAY 2013 01:23:39,321 --> 01:23:40,823 IT WORKS, BUT SOME OF THE LESS 2014 01:23:40,823 --> 01:23:44,093 COMMONLY FEATURED PROBLEMS FROM 2015 01:23:44,093 --> 01:23:44,960 SICKLE CELL DISEASE IS THAT IT 2016 01:23:44,960 --> 01:23:49,331 HAS AN ELEVATED TIMELINE RISK 2017 01:23:49,331 --> 01:23:50,866 FOR CEREBRAL INFARCTS AND STROKE 2018 01:23:50,866 --> 01:23:52,601 AND THIS CAN SIGNIFICANTLY 2019 01:23:52,601 --> 01:23:53,469 DECREASE PATIENTS' QUALITY OF 2020 01:23:53,469 --> 01:23:54,470 LIFE AND OVERALL ABILITY TO 2021 01:23:54,470 --> 01:23:55,137 FUNCTION. 2022 01:23:55,137 --> 01:23:56,939 WHAT WE SEE HERE IS A 2023 01:23:56,939 --> 01:23:57,606 21-YEAR-OLD AFRICAN AMERICAN 2024 01:23:57,606 --> 01:24:00,676 MALE WITH HBSS PHENOTYPE, AND 2025 01:24:00,676 --> 01:24:03,512 THE MR IMAGES COLLECTED HERE 2026 01:24:03,512 --> 01:24:12,454 SHOW SILENT CEREBRAL INFARCT 2027 01:24:12,454 --> 01:24:13,455 PRESENCE. 2028 01:24:13,455 --> 01:24:14,757 UNFORTUNATELY, PREVALENCE FOR 2029 01:24:14,757 --> 01:24:16,525 THE SILENT CEREBRAL INFARCTS 2030 01:24:16,525 --> 01:24:17,359 INCREASES THROUGHOUT THEIR LIFE 2031 01:24:17,359 --> 01:24:20,462 WITH NO OBVIOUS CEILING EFFECT 2032 01:24:20,462 --> 01:24:22,564 SEEN. 2033 01:24:22,564 --> 01:24:26,401 A STUDY THAT WAS SHOWN BY 2034 01:24:26,401 --> 01:24:28,070 DR. KASSIM SHOWS AS AGE 2035 01:24:28,070 --> 01:24:30,339 INCREASES, THE PREVALENCE FOR 2036 01:24:30,339 --> 01:24:31,540 THESE SILENT CEREBRAL INFARCT 2037 01:24:31,540 --> 01:24:33,175 ALSO INCREASES SO THAT BY AGE 2038 01:24:33,175 --> 01:24:35,244 30, MORE THAN 50% OF PATIENTS 2039 01:24:35,244 --> 01:24:37,179 HAVE A DETECTABLE SIGH LEAPT 2040 01:24:37,179 --> 01:24:43,519 CEREBRAL INFARCT. 2041 01:24:43,519 --> 01:24:45,154 UNFORTUNATELY, THE PRESENCE OF 2042 01:24:45,154 --> 01:24:46,355 SILENT CEREBRAL INFARCTS 2043 01:24:46,355 --> 01:24:48,457 INCREASES THE RISK FOR NEW OR 2044 01:24:48,457 --> 01:24:49,625 PROGRESSIVE INFARCTS, SO 2045 01:24:49,625 --> 01:24:51,160 FOLLOWING UP PATIENTS WHO HAVE 2046 01:24:51,160 --> 01:24:52,795 SHOWN SILENT CEREBRAL INFARCTS 2047 01:24:52,795 --> 01:24:54,329 AT BASELINE WHEN THEY WERE 2048 01:24:54,329 --> 01:24:55,097 MEASURED. 2049 01:24:55,097 --> 01:24:57,166 AFTER 2 1/2 YEARS, 30% OF THOSE 2050 01:24:57,166 --> 01:25:00,669 PATIENTS SHOWED A NEW OR 2051 01:25:00,669 --> 01:25:03,605 PROGRESSIVE INFARCTS, AND AT 2052 01:25:03,605 --> 01:25:05,140 FOLLOW-UP TIME OF UP TO FOUR 2053 01:25:05,140 --> 01:25:06,775 YEARS, 50% OF THESE PATIENTS 2054 01:25:06,775 --> 01:25:08,844 SHOWED PROGRESSION OR NEW 2055 01:25:08,844 --> 01:25:14,316 INFARCTS. 2056 01:25:14,316 --> 01:25:15,050 ONE OF THE THINGS THAT'S 2057 01:25:15,050 --> 01:25:17,486 IMPORTANT FOR REGULATING THE 2058 01:25:17,486 --> 01:25:19,521 BRAIN IS THAT IT ONLY COMPRISES 2059 01:25:19,521 --> 01:25:21,757 2% OF OUR BODY WEIGHT BUT IT 2060 01:25:21,757 --> 01:25:23,058 CONSUMES 20% OF THE ENERGY THAT 2061 01:25:23,058 --> 01:25:24,560 WE INTAKE THROUGHOUT OUR BODY, 2062 01:25:24,560 --> 01:25:26,094 AND IT DOESN'T HAVE A METABOLIC 2063 01:25:26,094 --> 01:25:27,729 RESERVE TO DRAW FROM UNLIKE SOME 2064 01:25:27,729 --> 01:25:30,132 OTHER AREAS OF OUR BODY. 2065 01:25:30,132 --> 01:25:32,801 SO MAINTAINING A CEREBRAL 2066 01:25:32,801 --> 01:25:35,037 METABOLIC RATE OF OXYGEN OR 2067 01:25:35,037 --> 01:25:36,738 CMRO2 IS REALLY IMPORTANT. 2068 01:25:36,738 --> 01:25:38,507 SO IN THE SCHEMATIC THAT I'VE 2069 01:25:38,507 --> 01:25:41,543 DISPLAYED HERE, THE CEREBRAL 2070 01:25:41,543 --> 01:25:42,644 METABOLIC RATE OF OXYGEN NEEDS 2071 01:25:42,644 --> 01:25:44,146 TO BE MAINTAINED AT A CONSTANT 2072 01:25:44,146 --> 01:25:45,981 RATE SHOWN IN GREEN, BUT FOR 2073 01:25:45,981 --> 01:25:47,983 SICKLE CELL PATIENTS WHO HAVE 2074 01:25:47,983 --> 01:25:52,588 INCREASED OXYGEN DELIVERY DUE TO 2075 01:25:52,588 --> 01:25:53,689 HEMOLYSIS, THE COMPLEX 2076 01:25:53,689 --> 01:25:58,460 MECHANISMS THAT ARE FORMED 2077 01:25:58,460 --> 01:25:59,461 INCLUDE -- ONCE THAT'S MAXED 2078 01:25:59,461 --> 01:26:04,566 OUT, BOT DE THE BODY CAN ALSO IE 2079 01:26:04,566 --> 01:26:05,901 THE OXYGEN EXTRACTION FRACTION 2080 01:26:05,901 --> 01:26:09,338 TO MAINTAIN THIS CEREBRAL 2081 01:26:09,338 --> 01:26:11,240 METABOLIC RATE OF OXYGEN. 2082 01:26:11,240 --> 01:26:13,575 THIS GETS WORSE AND WORSE AS THE 2083 01:26:13,575 --> 01:26:15,944 DISEASE BECOMES MORE SEVERE. 2084 01:26:15,944 --> 01:26:18,046 THERE'S AN EQUATION THAT YOU CAN 2085 01:26:18,046 --> 01:26:20,749 USE TO MEASURE THE CEREBRAL 2086 01:26:20,749 --> 01:26:21,917 METABOLIC RATE OF OXYGEN, AND 2087 01:26:21,917 --> 01:26:24,119 THAT'S BASICALLY JUST EQUAL TO 2088 01:26:24,119 --> 01:26:25,420 THE CEREBRAL BLOOD FLOW TIMES 2089 01:26:25,420 --> 01:26:27,256 THE OXYGEN EXTRACTION FRACTION 2090 01:26:27,256 --> 01:26:30,993 TIMES THE ARTERIAL OXYGEN 2091 01:26:30,993 --> 01:26:32,227 SATURATION MULTIPLIED BY THE 2092 01:26:32,227 --> 01:26:34,162 OXYGEN CARRYING CAPACITY OF 2093 01:26:34,162 --> 01:26:36,098 HEMOGLOBIN AND THE AMOUNT OF 2094 01:26:36,098 --> 01:26:36,999 HEMOGLOBIN A PATIENT HAS IN 2095 01:26:36,999 --> 01:26:37,966 THEIR BLOOD. 2096 01:26:37,966 --> 01:26:41,003 BUT THOSE TWO FACTORS ARE TWO 2097 01:26:41,003 --> 01:26:42,404 THINGS THAT HAVE BEEN IDENTIFIED 2098 01:26:42,404 --> 01:26:44,172 AS POSSIBLE BIOMARKERS FOR 2099 01:26:44,172 --> 01:26:45,908 TREATMENT SELECTION OR 2100 01:26:45,908 --> 01:26:47,309 EVALUATING TREATMENT RESPONSE ON 2101 01:26:47,309 --> 01:26:48,343 BRAIN HEALTH IN THESE PATIENTS 2102 01:26:48,343 --> 01:26:50,712 THAT ARE AT HIGH RISK FOR STROKE 2103 01:26:50,712 --> 01:26:55,918 AND CEREBRAL INFARCTS. 2104 01:26:55,918 --> 01:26:57,920 SO THE MOTIVATION BEHIND THIS 2105 01:26:57,920 --> 01:26:58,787 STUDY WAS ABOUT PATIENTS WHO 2106 01:26:58,787 --> 01:27:01,089 WERE RECEIVING HAPLOIDENTICAL 2107 01:27:01,089 --> 01:27:01,723 BONE MARROW TRANSPLANT OR I'M 2108 01:27:01,723 --> 01:27:03,225 JUST GOING TO CALL IT 2109 01:27:03,225 --> 01:27:04,359 TRANSPLANT, HAS BETTER 2110 01:27:04,359 --> 01:27:06,061 AVAILABILITY THAN STANDARD BONE 2111 01:27:06,061 --> 01:27:07,362 MARROW TRANSPLANT AND 2112 01:27:07,362 --> 01:27:08,563 PRELIMINARY EVIDENCE IN A GROUP 2113 01:27:08,563 --> 01:27:10,966 FROM OUR LAB IN FOUR ADULTS 2114 01:27:10,966 --> 01:27:13,135 SUGGEST THAT PATIENTS WHO 2115 01:27:13,135 --> 01:27:14,036 RECEIVED HAPLOIDENTICAL BONE 2116 01:27:14,036 --> 01:27:15,570 MARROW TRANSPLANT SHOWED MARKED 2117 01:27:15,570 --> 01:27:18,840 IMPROVEMENTS IN THEIR CEREBRAL 2118 01:27:18,840 --> 01:27:20,142 HEMODYNAMICS WHICH WOULD LIKELY 2119 01:27:20,142 --> 01:27:22,878 REDUCE THE RISK FOR THEIR -- 2120 01:27:22,878 --> 01:27:24,079 DEVELOPMENT OR STROKE 2121 01:27:24,079 --> 01:27:24,613 OCCURRENCE. 2122 01:27:24,613 --> 01:27:27,082 THE THREE MAIN HYPOTHESES HERE 2123 01:27:27,082 --> 01:27:28,483 IS THAT CEREBRAL BLOOD FLOW 2124 01:27:28,483 --> 01:27:29,351 WOULD REDUCE FOLLOWING 2125 01:27:29,351 --> 01:27:30,452 TRANSPLANT THAT WOULD APPROACH 2126 01:27:30,452 --> 01:27:32,254 THAT OF HEALTHY CONTROLS. 2127 01:27:32,254 --> 01:27:33,722 IMAGING MARKERS FOR CAPILLARY 2128 01:27:33,722 --> 01:27:35,223 SHUPTING WHICH IS ANOTHER WAY TO 2129 01:27:35,223 --> 01:27:38,160 LOOK AT CEREBRAL BLOOD FLOW 2130 01:27:38,160 --> 01:27:39,027 MEASURES WOULD REDUCE FOLLOWING 2131 01:27:39,027 --> 01:27:40,262 TRANSPLANT, AND THAT SECOND 2132 01:27:40,262 --> 01:27:41,463 FACTOR OXYGEN EXTRACTION 2133 01:27:41,463 --> 01:27:42,764 FRACTION WOULD ALSO REDUCE 2134 01:27:42,764 --> 01:27:43,532 FOLLOWING TRANSPLANT. 2135 01:27:43,532 --> 01:27:48,670 THIS IS REALLY IMPORTANT BECAUSE 2136 01:27:48,670 --> 01:27:51,406 UNDERSTANDING HOW THESE CEREBRAL 2137 01:27:51,406 --> 01:27:52,908 HEMODYNAMIC CHANGES IMPROVE 2138 01:27:52,908 --> 01:27:54,109 FOLLOWING TRANSPLANT CAN AID IN 2139 01:27:54,109 --> 01:27:56,311 THE DECISION-MAKING FOR 2140 01:27:56,311 --> 01:27:57,412 THERAPEUTIC INTERVENTIONS, 2141 01:27:57,412 --> 01:27:59,448 ESPECIALLY BECAUSE THERE'S NO 2142 01:27:59,448 --> 01:28:00,782 GOLD STANDARD FOR CURRENTLY 2143 01:28:00,782 --> 01:28:01,850 STRATIFYING PATIENTS INTO MORE 2144 01:28:01,850 --> 01:28:06,088 ADDRESMOREAGGRESSIVE THERAPIES E 2145 01:28:06,088 --> 01:28:08,523 TRANSFUSION OR TRANSPLANT, OR AS 2146 01:28:08,523 --> 01:28:10,258 WE'VE ALL SEEN NOW, BRAND NEW 2147 01:28:10,258 --> 01:28:10,826 GENE THERAPIES. 2148 01:28:10,826 --> 01:28:13,395 SO UNDERSTANDING HOW THESE ARE 2149 01:28:13,395 --> 01:28:15,263 CHANGING CAN AID IN 2150 01:28:15,263 --> 01:28:16,698 DECISION-MAKING FOR THE KIND OF 2151 01:28:16,698 --> 01:28:17,532 THERAPEUTIC INTERVENTIONS WE 2152 01:28:17,532 --> 01:28:21,069 WANT TO SEE IN PATIENTS WHO ARE 2153 01:28:21,069 --> 01:28:22,170 AT PARTICULARLY HIGH RISK FOR 2154 01:28:22,170 --> 01:28:22,504 STROKE. 2155 01:28:22,504 --> 01:28:24,339 HERE WE HAVE 39 ADULTS 2156 01:28:24,339 --> 01:28:25,107 PARTICIPANT IN TOTAL. 2157 01:28:25,107 --> 01:28:26,541 WE HAD 11 SICKLE CELL DISEASE 2158 01:28:26,541 --> 01:28:27,943 PATIENTS WHO WERE ALL CANDIDATE 2159 01:28:27,943 --> 01:28:30,445 FOR TRANSPLANT AND 28 AGE AND 2160 01:28:30,445 --> 01:28:31,446 SEX-MATCHED CONTROLS. 2161 01:28:31,446 --> 01:28:32,647 WE GOT SOME BLOOD WORK FROM THEM 2162 01:28:32,647 --> 01:28:34,716 THAT LOOKED AT TOTAL HEMOGLOBIN 2163 01:28:34,716 --> 01:28:38,320 AND HEMOGLOBIN S FRACTION 2164 01:28:38,320 --> 01:28:41,490 MEASURED BY VENIPUNCTURE AND 2165 01:28:41,490 --> 01:28:42,758 ARTERIAL OXYGEN SATURATION 2166 01:28:42,758 --> 01:28:45,494 MEASURED VIA PULSE OXIMETRY AT 2167 01:28:45,494 --> 01:28:46,862 THE SAME TIME THEY RECEIVED 2168 01:28:46,862 --> 01:28:47,496 THEIR IMAGING. 2169 01:28:47,496 --> 01:28:50,098 ALL OF THE PATIENTS UNDERWENT 2170 01:28:50,098 --> 01:28:51,833 MAGNETIC RESONANCE IMAGING. 2171 01:28:51,833 --> 01:28:56,104 WE COLLECTED SOME STANDARD 2172 01:28:56,104 --> 01:28:57,072 ANATOMICAL IMAGES AND 2173 01:28:57,072 --> 01:28:58,740 IMPORTANTLY TO MEASURE CEREBRAL 2174 01:28:58,740 --> 01:29:04,379 BLOOD FLOW, WE USED A 2D 2175 01:29:04,379 --> 01:29:06,381 CONTINUE ONCE SPATIAL RESOLUTION 2176 01:29:06,381 --> 01:29:09,317 TECHNIQUE. 2177 01:29:09,317 --> 01:29:11,053 TO LOOK AT OUR FIRST HYPOTHESIS, 2178 01:29:11,053 --> 01:29:13,789 WE DO SEE CEREBRAL BLOOD FLOW 2179 01:29:13,789 --> 01:29:15,090 SIGNIFICANTLY DECREASES 2180 01:29:15,090 --> 01:29:15,957 FOLLOWING TRANSPLANT, AND YOU 2181 01:29:15,957 --> 01:29:18,593 CAN SEE THAT QUANTIFIED IN THE 2182 01:29:18,593 --> 01:29:20,595 MIDDLE AREA HERE ON THIS VIOLIN 2183 01:29:20,595 --> 01:29:21,096 PLOT. 2184 01:29:21,096 --> 01:29:22,764 EACH PATIENT IS SHOWN 2185 01:29:22,764 --> 01:29:23,698 INDIVIDUALLY WITH A LINE 2186 01:29:23,698 --> 01:29:25,700 CONNECTING THEIR PRETRANSPLANT 2187 01:29:25,700 --> 01:29:27,636 ON THE LEFT POST TRANSPLANT 2188 01:29:27,636 --> 01:29:28,937 CEREBRAL BLOOD FLOW VALUES ON 2189 01:29:28,937 --> 01:29:29,604 THE RIGHT. 2190 01:29:29,604 --> 01:29:32,240 AND REALLY IMPORTANTLY HERE, WE 2191 01:29:32,240 --> 01:29:34,109 SEE THAT THESE DECREASES IN 2192 01:29:34,109 --> 01:29:35,277 CEREBRAL BLOOD FLOW DROP TO THAT 2193 01:29:35,277 --> 01:29:39,448 OF HEALTHY CONTROLS, SO IN THE 2194 01:29:39,448 --> 01:29:41,716 PLOT ON THE FAR RIGHT-HAND SIDE, 2195 01:29:41,716 --> 01:29:42,984 HEALTHY CONTROLS ARE SHOWN ON 2196 01:29:42,984 --> 01:29:45,887 THE LEFT. 2197 01:29:45,887 --> 01:29:46,888 OUR PRETRANSPLANT PATIENTS ARE 2198 01:29:46,888 --> 01:29:48,924 SHOWN IN THE MIDDLE AND POST 2199 01:29:48,924 --> 01:29:49,624 TRANSPLANT ARE ON THE RIGHT 2200 01:29:49,624 --> 01:29:51,259 WHERE YOU CAN SEE FROM PRE TO 2201 01:29:51,259 --> 01:29:52,527 POST TRANSPLANT, THOSE VALUES 2202 01:29:52,527 --> 01:29:54,796 DROPPED TO THOSE COMPARABLE TO 2203 01:29:54,796 --> 01:29:55,464 PATIENTS' CEREBRAL BLOOD FLOW 2204 01:29:55,464 --> 01:29:57,299 WHO DON'T HAVE SICKLE CELL 2205 01:29:57,299 --> 01:30:03,238 DISEASE. 2206 01:30:03,238 --> 01:30:04,539 ANOTHER WAY TO LOOK AT THIS 2207 01:30:04,539 --> 01:30:06,708 INFORMATION IS TO USE THESE HEAT 2208 01:30:06,708 --> 01:30:08,477 MAPS FOR BLOOD FLOW, SO THESE 2209 01:30:08,477 --> 01:30:10,011 ARE ASCENDING AXIAL SLICES OF 2210 01:30:10,011 --> 01:30:10,979 THE BRAIN WHERE THE BOTTOM OF 2211 01:30:10,979 --> 01:30:12,781 THE BRAIN IS SHOWN IN THE TOP 2212 01:30:12,781 --> 01:30:14,249 LEFT AND THE TOP OF THE BRAIN IS 2213 01:30:14,249 --> 01:30:15,450 SHOWN ON THE BOTTOM RIGHT. 2214 01:30:15,450 --> 01:30:18,019 AND THIS IS AN AVERAGE LOOK AT 2215 01:30:18,019 --> 01:30:21,890 CEREBRAL BLOOD FLOW AYOS ALL OFL 2216 01:30:21,890 --> 01:30:25,160 OF OUR TRANSPLANT PATIENTS. 2217 01:30:25,160 --> 01:30:27,562 ON THE LEFT-HAND SIDE IS 2218 01:30:27,562 --> 01:30:28,330 PRETRANSPLANT, ON THE RIGHT-HAND 2219 01:30:28,330 --> 01:30:29,197 SIDE IS POST TRANSPLANT. 2220 01:30:29,197 --> 01:30:31,066 YOU CAN REALLY JUST APPRECIATE 2221 01:30:31,066 --> 01:30:33,235 HERE THAT ELEVATED TRANSPLANT -- 2222 01:30:33,235 --> 01:30:36,872 OR ELEVATED BLOOD FLOW SHOWN IN 2223 01:30:36,872 --> 01:30:38,807 THE HOT COLORS HERE DECREASES 2224 01:30:38,807 --> 01:30:40,909 SIGNIFICANTLY FOLLOWING 2225 01:30:40,909 --> 01:30:42,544 TRANSPLANT, SO THAT THE AVERAGE 2226 01:30:42,544 --> 01:30:45,313 HOVERS MUCH CLOSER TO LIKE 45 OR 2227 01:30:45,313 --> 01:30:47,449 50. 2228 01:30:47,449 --> 01:30:52,587 50 FOLLOWING TRANSPLANT. 2229 01:30:52,587 --> 01:30:56,024 ADDITIONALLY ANOTHER WAY TO LOCK 2230 01:30:56,024 --> 01:30:57,259 AT CEREBRAL BLOOD FLOW IS TO 2231 01:30:57,259 --> 01:30:59,561 LOOK AT THIS CAPILLARY SHUNTING 2232 01:30:59,561 --> 01:31:00,829 EFFECT WHICH IS THE IDEA THAT 2233 01:31:00,829 --> 01:31:02,364 HIGH BLOOD FLOW VELOCITIES 2234 01:31:02,364 --> 01:31:08,170 RESULT IN RAPID BLOOD CELL 2235 01:31:08,170 --> 01:31:09,471 TRANSIT THROUGH CEREBRAL 2236 01:31:09,471 --> 01:31:10,005 CAPILLARIES. 2237 01:31:10,005 --> 01:31:17,012 THIS REDUCES CAPILLARY -- THAT'S 2238 01:31:17,012 --> 01:31:20,415 INDICATIVE WE THINK OF 2239 01:31:20,415 --> 01:31:23,685 SUBOPTIMAL DELIVERY WHICH IS 2240 01:31:23,685 --> 01:31:24,653 STRESSFUL ON THE TISSUE AND CAN 2241 01:31:24,653 --> 01:31:25,754 RESULT IN SOME OF THESE 2242 01:31:25,754 --> 01:31:26,087 INFARCTS. 2243 01:31:26,087 --> 01:31:30,892 SO WE CAN LOOK AT THIS ON AN 2244 01:31:30,892 --> 01:31:33,728 ARTERIAL SPIN LABELING SCAN BY 2245 01:31:33,728 --> 01:31:35,363 LOOKING AT THE SUPERIOR SAGITTAL 2246 01:31:35,363 --> 01:31:35,697 SINUS. 2247 01:31:35,697 --> 01:31:36,798 JUST AS A QUICK REVIEW FOR 2248 01:31:36,798 --> 01:31:38,366 ANYBODY WHO DOESN'T LOOK AT THE 2249 01:31:38,366 --> 01:31:39,968 BRAIN A LOT, THERE'S A HUGE 2250 01:31:39,968 --> 01:31:41,169 DRAINING VEIN YOU CAN SEE THAT'S 2251 01:31:41,169 --> 01:31:42,170 RIGHT ALONG THE MIDLINE IN THE 2252 01:31:42,170 --> 01:31:42,470 BRAIN. 2253 01:31:42,470 --> 01:31:44,773 IF YOU CUT THAT AND LOOK AT THIS 2254 01:31:44,773 --> 01:31:45,640 FIGURE ON THE RIGHT-HAND SIDE 2255 01:31:45,640 --> 01:31:47,042 HERE, YOU CAN SEE THAT EACH 2256 01:31:47,042 --> 01:31:48,877 PATIENT SHOWS A SIGNIFICANT 2257 01:31:48,877 --> 01:31:50,445 DECREASE IN THEIR SUPERIOR 2258 01:31:50,445 --> 01:31:52,080 SAGITTAL SINUS WILL SIGNAL FOR 2259 01:31:52,080 --> 01:32:01,456 SINUS SIGNAL.HIGH BLOOD FLOW VAN 2260 01:32:01,456 --> 01:32:07,128 IN THAT RED HOT COLOR AND LOWER 2261 01:32:07,128 --> 01:32:11,800 BLOOD FLOW VALUES IN THOSE BLUE 2262 01:32:11,800 --> 01:32:12,567 COOL COLORS. 2263 01:32:12,567 --> 01:32:13,535 FINALLY, WE'RE INTERESTED IN 2264 01:32:13,535 --> 01:32:14,970 THESE OXYGEN EXTRACTION FRACTION 2265 01:32:14,970 --> 01:32:17,439 CHANGES THAT WERE RELATED TO 2266 01:32:17,439 --> 01:32:17,906 THEIR TRANSPLANT. 2267 01:32:17,906 --> 01:32:21,409 WE DON'T SEE SIGNIFICANT CHANGES 2268 01:32:21,409 --> 01:32:24,012 FOLLOWING TRANSPLANT, BUT WE DO 2269 01:32:24,012 --> 01:32:26,748 SEE THAT PATIENTS WHO HAD 2270 01:32:26,748 --> 01:32:28,383 SIGNIFICANTLY ELEVATED OXYGEN 2271 01:32:28,383 --> 01:32:30,852 EXTRACTION FRACTION PERCENTAGES 2272 01:32:30,852 --> 01:32:32,087 PRETRANSPLANT TEND TO SHOW 2273 01:32:32,087 --> 01:32:34,589 IMPROVEMENTS IN OXYGEN 2274 01:32:34,589 --> 01:32:35,257 EXTRACTION FRACTION FOLLOWING 2275 01:32:35,257 --> 01:32:35,657 TRANSPLANT. 2276 01:32:35,657 --> 01:32:38,226 SO IF YOU LOOK AT THE GRAPH, THE 2277 01:32:38,226 --> 01:32:40,328 LINEAR REGRESSION GRAPH ON THE 2278 01:32:40,328 --> 01:32:44,766 RIGHT HERE AND YOU WERE TO DRAW 2279 01:32:44,766 --> 01:32:47,202 A LINE, SO AN AVERAGE HEALTHY 2280 01:32:47,202 --> 01:32:48,169 CONSIDERED OXYGEN EXTRACTION 2281 01:32:48,169 --> 01:32:51,806 FRACTION IS ABOUT 35%, AND A 2282 01:32:51,806 --> 01:32:53,208 STANDARD DEVIATION ABOVE THAT IS 2283 01:32:53,208 --> 01:32:53,775 ABOUT 42%. 2284 01:32:53,775 --> 01:32:56,044 SO IF YOU LOOK AT EVERYONE ON 2285 01:32:56,044 --> 01:32:57,712 THIS GRAPH WHO HAD AN ELEVATED 2286 01:32:57,712 --> 01:33:00,315 EXTRACTION FRACTION 2287 01:33:00,315 --> 01:33:01,950 PRETRANSPLANT THAT WAS GREATER 2288 01:33:01,950 --> 01:33:03,585 THAN 42%, ALMOST ALL OF THOSE 2289 01:33:03,585 --> 01:33:05,153 PATIENTS SHOWED DECREASES IN 2290 01:33:05,153 --> 01:33:08,323 THEIR OXYGEN EXTRACTION FRACTION 2291 01:33:08,323 --> 01:33:09,057 FOLLOWING TRANSPLANT. 2292 01:33:09,057 --> 01:33:10,392 PATIENTS WHO WERE ALREADY ON 2293 01:33:10,392 --> 01:33:11,259 THAT FAR RIGHT-HAND SHIFT OF 2294 01:33:11,259 --> 01:33:13,561 THAT CURVE TO TRY AND MAINTAIN 2295 01:33:13,561 --> 01:33:15,297 THEIR CEREBRAL METABOLIC RATE OF 2296 01:33:15,297 --> 01:33:17,165 OXYGEN DO SHOW IMPROVEMENTS IN 2297 01:33:17,165 --> 01:33:20,835 THEIR OXYGEN EXTRACTION FRACK FN 2298 01:33:20,835 --> 01:33:23,805 FOLLOWING TRANSPLANT. 2299 01:33:23,805 --> 01:33:25,073 SOME LIMITATIONS FOR THE STUDY 2300 01:33:25,073 --> 01:33:26,741 IS THAT IT IS, IN FACT, A SMALL 2301 01:33:26,741 --> 01:33:28,710 SAMPLE SIZE. 2302 01:33:28,710 --> 01:33:29,277 IT'S 11 PATIENTS. 2303 01:33:29,277 --> 01:33:31,446 SO FURTHER RESEARCH IS NEEDED TO 2304 01:33:31,446 --> 01:33:32,981 UNDERSTAND HOW BIOMARKERS OF 2305 01:33:32,981 --> 01:33:34,616 BRAIN HEALTH CAN REALLY WORK. 2306 01:33:34,616 --> 01:33:36,484 AND THAT CLINICAL INDICATIONS 2307 01:33:36,484 --> 01:33:38,119 FOR TRANSPLANT WERE VARIED FOR 2308 01:33:38,119 --> 01:33:39,087 OUR PATIENT POPULATION. 2309 01:33:39,087 --> 01:33:40,722 NOT EVERYONE HAD A NEUROLOGICAL 2310 01:33:40,722 --> 01:33:42,424 INDICATION FOR TRANSPLANT. 2311 01:33:42,424 --> 01:33:44,492 AND THAT COULD POSSIBLY VARY 2312 01:33:44,492 --> 01:33:46,861 EACH PATIENT'S CEREBRAL 2313 01:33:46,861 --> 01:33:47,362 COMPENSATION MECHANISMS. 2314 01:33:47,362 --> 01:33:49,364 SO LIKE I SHOWED IN THE OXYGEN 2315 01:33:49,364 --> 01:33:50,565 EXTRACTION FRACTION GRAPH, NOT 2316 01:33:50,565 --> 01:33:52,100 EVERYBODY HAD HIGHLY ELEVATED 2317 01:33:52,100 --> 01:33:54,502 OXYGEN FRACTION PERCENTAGES 2318 01:33:54,502 --> 01:33:56,938 COMPARED TO WHAT A HEALTHY 2319 01:33:56,938 --> 01:33:58,573 CONTROL MIGHT BE WHICH IS AROUND 2320 01:33:58,573 --> 01:34:04,112 35%. 2321 01:34:04,112 --> 01:34:06,114 AND ALTHOUGH IT IS ONLY 11 2322 01:34:06,114 --> 01:34:07,849 PATIENTS, IT IS NOVEL INSIGHTS 2323 01:34:07,849 --> 01:34:10,251 INTO WHAT WE WOULD KIND OF 2324 01:34:10,251 --> 01:34:12,787 CONSIDERED TO BE A LARGER COHORT 2325 01:34:12,787 --> 01:34:14,089 OF ADULT PATIENTS WHO ARE 2326 01:34:14,089 --> 01:34:15,757 UNDERGOING THIS HAPLOIDENTICAL 2327 01:34:15,757 --> 01:34:18,560 BONE MARROW TRANSPLANT PROTOCOL. 2328 01:34:18,560 --> 01:34:20,662 AND HERE WE SEE THAT ELEVATED 2329 01:34:20,662 --> 01:34:22,063 CEREBRAL BLOOD FLOW IN OUR 2330 01:34:22,063 --> 01:34:23,298 SICKLE CELL PATIENTS DECREASES 2331 01:34:23,298 --> 01:34:24,499 FOLLOWING TRANSPLANT BUT DOESN'T 2332 01:34:24,499 --> 01:34:26,101 JUST DECREASE, IT DECREASES TO 2333 01:34:26,101 --> 01:34:27,168 VALUES SIMILAR TO HEALTHY 2334 01:34:27,168 --> 01:34:28,069 ADULTS. 2335 01:34:28,069 --> 01:34:30,338 AND WE SEE THAT THIS CAPILLARY 2336 01:34:30,338 --> 01:34:32,574 SHUNTING EFFECT IS AMELIORATED 2337 01:34:32,574 --> 01:34:33,742 FOLLOWING TRANSPLANT IN A 2338 01:34:33,742 --> 01:34:35,944 SUPERIOR SAGITTAL SINUS, SO THAT 2339 01:34:35,944 --> 01:34:38,012 IMPROVES SIGNIFICANTLY. 2340 01:34:38,012 --> 01:34:38,780 WHICH WE THINK IS GOING TO HELP 2341 01:34:38,780 --> 01:34:41,216 WITH THAT OXYGEN OFFLOADING EE 2342 01:34:41,216 --> 01:34:44,886 QISH EFFICIENEFFICIENCY AND GETE 2343 01:34:44,886 --> 01:34:45,787 OXYGEN TO THE TISSUE. 2344 01:34:45,787 --> 01:34:48,523 PATIENTS WHO SHOW SIGNIFICANTLY 2345 01:34:48,523 --> 01:34:49,391 ELEVATED OXYGEN EJECTION 2346 01:34:49,391 --> 01:34:53,094 FRACTION AT BASELINE AT 42% SHOW 2347 01:34:53,094 --> 01:34:54,429 THE STRONGEST IMPROVEMENTS IN 2348 01:34:54,429 --> 01:34:56,331 THEIR OXYGEN METABOLISM OVERALL. 2349 01:34:56,331 --> 01:34:58,366 WE REALLY THINK THAT CEREBRAL 2350 01:34:58,366 --> 01:35:00,135 BLOOD FLOW CAN BE USED AS A 2351 01:35:00,135 --> 01:35:01,703 NONINVASIVE IMAGING BIOMARKER 2352 01:35:01,703 --> 01:35:02,804 FOR CEREBROVASCULAR HEALTH ON 2353 01:35:02,804 --> 01:35:07,575 THE WHOLE. 2354 01:35:07,575 --> 01:35:09,310 AND WITH THAT, I'D LIKE TO 2355 01:35:09,310 --> 01:35:10,111 ACKNOWLEDGE MY LAB. 2356 01:35:10,111 --> 01:35:11,646 NONE OF THIS IS DONE IN 2357 01:35:11,646 --> 01:35:12,280 ISOLATION OBVIOUSLY. 2358 01:35:12,280 --> 01:35:13,148 IT'S A TEAM EFFORT. 2359 01:35:13,148 --> 01:35:14,682 SO THANKS SO MUCH TO MY LAB AND 2360 01:35:14,682 --> 01:35:15,784 ALL OF THE WORK THAT EVERYONE 2361 01:35:15,784 --> 01:35:16,651 HAS PUT IN. 2362 01:35:16,651 --> 01:35:21,556 AND OUR FUNDING SOURCES. 2363 01:35:21,556 --> 01:35:22,791 AND SPECIAL ATTENTION TO THE 2364 01:35:22,791 --> 01:35:23,858 PATIENTS WHO VOLUNTEER THEIR 2365 01:35:23,858 --> 01:35:25,627 TIME AND EFFORT. 2366 01:35:25,627 --> 01:35:26,895 THIS IS A HUGE, HUGE TIME 2367 01:35:26,895 --> 01:35:28,196 COMMITMENT FOR THEM, AND THIS 2368 01:35:28,196 --> 01:35:29,631 WOULD NOT BE POSSIBLE WITHOUT 2369 01:35:29,631 --> 01:35:29,831 THEM. 2370 01:35:29,831 --> 01:35:35,637 THANK YOU. 2371 01:35:35,637 --> 01:35:35,904 [APPLAUSE] 2372 01:35:35,904 --> 01:35:40,475 >> THANK YOU, DR. AUMANN. 2373 01:35:40,475 --> 01:35:42,477 FOR THE SAKE OF TIME WE NEED TO 2374 01:35:42,477 --> 01:35:43,912 MOVE ON BUT THERE'S A COMMENT IN 2375 01:35:43,912 --> 01:35:45,680 THE CHAT FOR YOU FROM 2376 01:35:45,680 --> 01:35:46,448 DR. WALTERS. 2377 01:35:46,448 --> 01:35:48,983 OUR FINAL SPEAKER IS DR. STACI 2378 01:35:48,983 --> 01:35:51,152 MARTIN FROM THE NATIONAL CANCER 2379 01:35:51,152 --> 01:35:52,020 INSTITUTE CENTER FOR CANCER 2380 01:35:52,020 --> 01:35:53,121 RESEARCH HERE AT THE NIH AND SHE 2381 01:35:53,121 --> 01:35:54,556 WILL BE PRESENTING ON COGNITIVE 2382 01:35:54,556 --> 01:35:56,157 AND EMOTIONAL WELL-BEING IN 2383 01:35:56,157 --> 01:35:56,825 INDIVIDUALS WITH SICKLE CELL 2384 01:35:56,825 --> 01:36:06,968 DISEASE. 2385 01:36:16,945 --> 01:36:18,947 >> SO IN TERMS OF 2386 01:36:18,947 --> 01:36:19,914 NEUROPSYCHOLOGICAL FUNCTIONING, 2387 01:36:19,914 --> 01:36:22,884 WE KNOW FROM THE LITERATURE THAT 2388 01:36:22,884 --> 01:36:24,052 ADULTS WITH SICKLE CELL ANEMIA 2389 01:36:24,052 --> 01:36:25,520 SCORE LOWER THAN HEALTHY 2390 01:36:25,520 --> 01:36:26,488 INDIVIDUALS IN PARTICULAR AREAS 2391 01:36:26,488 --> 01:36:28,790 SUCH AS VISUAL SPATIAL SKILLS, 2392 01:36:28,790 --> 01:36:30,024 WORKING MEMORY WHICH IS THE 2393 01:36:30,024 --> 01:36:31,626 ABILITY TO HOLD INFORMATION IN 2394 01:36:31,626 --> 01:36:33,928 YOUR MIND, AND PRODUCE A 2395 01:36:33,928 --> 01:36:36,798 RESPONSE FROM IT, PROCESSING 2396 01:36:36,798 --> 01:36:38,299 SPEED, ATTENTION, AND EXECUTIVE 2397 01:36:38,299 --> 01:36:39,300 FUNCTIONING, WHICH IS OTHERWISE 2398 01:36:39,300 --> 01:36:43,638 KNOWN AS COGNITIVE FLEXIBILITY 2399 01:36:43,638 --> 01:36:44,939 OR ABILITY TO SHIFT AND KIND OF 2400 01:36:44,939 --> 01:36:46,374 PLAN AND ORGANIZE YOUR THOUGHTS 2401 01:36:46,374 --> 01:36:46,908 AND BEHAVIOR. 2402 01:36:46,908 --> 01:36:50,078 THERE'S OTHER AREAS WHERE THEY 2403 01:36:50,078 --> 01:36:52,146 PERFORM EXRA BLI TO HEALTHY 2404 01:36:52,146 --> 01:36:55,550 CONTROLS, SUCH AS VERBAL 2405 01:36:55,550 --> 01:36:58,319 COMPREHENSION AND MOTOR SPEED. 2406 01:36:58,319 --> 01:36:59,387 THERE ARE HAS BEEN RESEARCH 2407 01:36:59,387 --> 01:37:01,923 SHOWING THAT THESE AREAS OF 2408 01:37:01,923 --> 01:37:04,225 STRENGTHS AND WEAKNESSES ARE 2409 01:37:04,225 --> 01:37:06,160 CONSISTENT WITH IMAGING 2410 01:37:06,160 --> 01:37:07,829 ABNORMALITIES ON SCANS. 2411 01:37:07,829 --> 01:37:09,230 PARTICULARLY IN AREAS SUCH AS 2412 01:37:09,230 --> 01:37:11,099 THE BASAL GANGLIA AND THE 2413 01:37:11,099 --> 01:37:12,100 FRONTAL LOBE, AND THAT'S WHERE 2414 01:37:12,100 --> 01:37:15,136 YOU'RE GOING TO FIND DEFICITS IN 2415 01:37:15,136 --> 01:37:17,472 THE PROCESSING SPEED, ATTENTION, 2416 01:37:17,472 --> 01:37:25,113 EXECUTIVE SKILLS AND SO ON. 2417 01:37:25,113 --> 01:37:26,281 SO AMONG CHILDREN AND 2418 01:37:26,281 --> 01:37:27,048 ADOLESCENTS WITH SICKLE CELL 2419 01:37:27,048 --> 01:37:30,118 DISEASE WHO UNDERGO A 2420 01:37:30,118 --> 01:37:32,887 HAPLOIDENTICAL BONE MARROW 2421 01:37:32,887 --> 01:37:33,955 TRANSPLANT, RESEARCH HAS SHOWN 2422 01:37:33,955 --> 01:37:34,956 IMPROVEMENTS IN PROCESSING 2423 01:37:34,956 --> 01:37:37,625 SPEED, SO HOW QUICKLY YOU 2424 01:37:37,625 --> 01:37:38,893 PROCESS INFORMATION, BUT THEY 2425 01:37:38,893 --> 01:37:40,461 HAVEN'T SHOWN ANY SIGNIFICANT 2426 01:37:40,461 --> 01:37:42,931 IMPROVEMENTS IN OTHER COGNITIVE 2427 01:37:42,931 --> 01:37:43,164 DOMAINS. 2428 01:37:43,164 --> 01:37:44,933 BUT WE DON'T KNOW AS MUCH YET 2429 01:37:44,933 --> 01:37:47,001 ABOUT COGNITIVE FUNCTIONING PRE 2430 01:37:47,001 --> 01:37:48,670 TO POST TRANSPLANT AMONG ADULTS 2431 01:37:48,670 --> 01:37:56,244 WITH SICKLE CELL. 2432 01:37:56,244 --> 01:37:58,313 SO OUR GROUP, THE HEALTH 2433 01:37:58,313 --> 01:38:00,315 PSYCHOLOGY AND NEUROBEHAVIORAL 2434 01:38:00,315 --> 01:38:02,717 RESEARCH GROUP AT THE NIH, WORKS 2435 01:38:02,717 --> 01:38:05,853 WITH THE NHLBI HERE ON A VARIETY 2436 01:38:05,853 --> 01:38:08,056 OF THEIR TRANSPLANT PROTOCOLS, 2437 01:38:08,056 --> 01:38:09,691 AND ON THESE TRANSPLANT 2438 01:38:09,691 --> 01:38:12,126 PROTOCOLS, WE HAVE EXAMINED 2439 01:38:12,126 --> 01:38:13,761 COGNITIVE AND EMOTIONAL 2440 01:38:13,761 --> 01:38:15,263 WELL-BEING AMONG INDIVIDUALS 2441 01:38:15,263 --> 01:38:16,230 WITH SICKLE CELL DISEASE, PRIME 2442 01:38:16,230 --> 01:38:19,100 LEA ADULTS, SOME CHILDREN. 2443 01:38:19,100 --> 01:38:21,603 AND OUR PRIMARY -- ANOTHER 2444 01:38:21,603 --> 01:38:22,904 PRIMARY AIM WAS TO DETERMINE HOW 2445 01:38:22,904 --> 01:38:26,874 FUNCTIONING CHANGES FROM PRE TO 2446 01:38:26,874 --> 01:38:27,408 POST TRANSPLANT. 2447 01:38:27,408 --> 01:38:29,811 SO WE COMPLETED PREHEN SIEVE 2448 01:38:29,811 --> 01:38:32,113 NEUROBEHAVIORAL ASSESSMENTS WITH 2449 01:38:32,113 --> 01:38:33,648 PATIENTS BEFORE TRANSPLANT AND 2450 01:38:33,648 --> 01:38:35,917 THEN 12 MONTHS AFTER TRANSPLANT 2451 01:38:35,917 --> 01:38:41,623 ON THESE SEVERAL PROTOCOLS. 2452 01:38:41,623 --> 01:38:43,925 SO WHAT DO WE ASSESS IN A 2453 01:38:43,925 --> 01:38:44,926 NEUROBEHAVIORAL ASSESSMENT? 2454 01:38:44,926 --> 01:38:46,861 WE LOOK FIRST AT VERBAL SKILLS, 2455 01:38:46,861 --> 01:38:48,730 SO YOUR ABILITY TO REASON USING 2456 01:38:48,730 --> 01:38:51,165 WORDS AND UNDERSTAND WHAT OTHER 2457 01:38:51,165 --> 01:38:57,705 PEOPLE SAY TO YOU. 2458 01:38:57,705 --> 01:38:59,774 AND THEN NON-VERBAL SKILLS, SO 2459 01:38:59,774 --> 01:39:01,009 VISUAL SPATIAL SKILLS, SOLVING 2460 01:39:01,009 --> 01:39:03,211 PROBLEMS BASED ON VISUAL 2461 01:39:03,211 --> 01:39:08,082 REASONING. 2462 01:39:08,082 --> 01:39:08,349 ATTENTION. 2463 01:39:08,349 --> 01:39:10,952 AND YOU CAN GO AHEAD AND GO -- 2464 01:39:10,952 --> 01:39:12,687 THERE YOU GO. 2465 01:39:12,687 --> 01:39:14,455 ATTENTION -- THANK YOU. 2466 01:39:14,455 --> 01:39:16,190 MEMORY, AND DIFFERENT KINDS OF 2467 01:39:16,190 --> 01:39:17,625 MEMORY, SHORT TERM MEMORY, LONG 2468 01:39:17,625 --> 01:39:19,961 TERM MEMORY, WORKING MEMORY. 2469 01:39:19,961 --> 01:39:21,696 PROCESSING SPEED AND THEN THAT 2470 01:39:21,696 --> 01:39:24,032 EXECUTIVE FUNCTIONING AREA THAT 2471 01:39:24,032 --> 01:39:34,442 I MENTIONED PREVIOUSLY. 2472 01:39:40,181 --> 01:39:41,482 THEN OTHER DOMAINS THAT WE LOOK 2473 01:39:41,482 --> 01:39:43,017 AT AS WELL IN THESE ASSESSMENTS 2474 01:39:43,017 --> 01:39:44,118 ARE THINGS LIKE A SOCIAL 2475 01:39:44,118 --> 01:39:46,120 EMOTIONAL WELL-BEING, SO WE GIVE 2476 01:39:46,120 --> 01:39:49,724 THE PROMIS, SUBSCALES FROM THE 2477 01:39:49,724 --> 01:39:53,561 PROMIS AND THE BRIEF SYMPTOM 2478 01:39:53,561 --> 01:39:54,429 INVENTORY, LOOKING AT THINGS 2479 01:39:54,429 --> 01:39:56,597 LIKE ANXIETY, DEPRESSION, 2480 01:39:56,597 --> 01:39:57,932 SOMATIZATION OR COMPLAINTS ABOUT 2481 01:39:57,932 --> 01:40:00,234 PHYSICAL SYMPTOMS AND SLEEP. 2482 01:40:00,234 --> 01:40:02,303 NOT ONLY DO WE GIVE EXECUTIVE 2483 01:40:02,303 --> 01:40:03,304 FUNCTIONING TESTS TO THE 2484 01:40:03,304 --> 01:40:04,839 PATIENTS, BUT WE ALSO GIVE THEM 2485 01:40:04,839 --> 01:40:06,040 A QUESTIONNAIRE, A 2486 01:40:06,040 --> 01:40:07,608 PATIENT-REPORTED OUTCOME MEASURE 2487 01:40:07,608 --> 01:40:09,444 WHERE THEY REPORT ON THEIR OWN 2488 01:40:09,444 --> 01:40:11,412 PERCEPTIONS OF THEIR DAY TO DAY 2489 01:40:11,412 --> 01:40:14,849 EXECUTIVE SKILLS. 2490 01:40:14,849 --> 01:40:16,017 THEN WE LOOK AT PAIN IN THE PAST 2491 01:40:16,017 --> 01:40:17,351 WEEK AND DURING THE TEST SESSION 2492 01:40:17,351 --> 01:40:19,187 AS WELL AS THE EXTENT TO WHICH 2493 01:40:19,187 --> 01:40:20,388 PAIN INTERFERES WITH DAILY 2494 01:40:20,388 --> 01:40:27,929 FUNCTIONING. 2495 01:40:27,929 --> 01:40:29,363 SO FOR THE FIRST STUDY THAT I'M 2496 01:40:29,363 --> 01:40:31,332 GOING TO BE TALKING ABOUT, WE 2497 01:40:31,332 --> 01:40:35,603 LOOKED AT 47 PATIENTS, AND THEN 2498 01:40:35,603 --> 01:40:36,704 22 OF THOSE PATIENTS HAD A 2499 01:40:36,704 --> 01:40:40,541 SIBLING DONOR, A MATCHED SIBLING 2500 01:40:40,541 --> 01:40:42,510 DONOR THAT ALSO PROVIDED DATA AT 2501 01:40:42,510 --> 01:40:44,145 BASE LIKE AND 12 MONTHS POST 2502 01:40:44,145 --> 01:40:49,083 TRANSPLANT. 2503 01:40:49,083 --> 01:40:51,252 AND WHAT WE'VE FOUND WAS THAT 2504 01:40:51,252 --> 01:40:52,587 AMONG THESE PATIENTS AND 2505 01:40:52,587 --> 01:40:54,756 SIBLINGS, ALL OF THE SCORES WERE 2506 01:40:54,756 --> 01:40:55,857 WITHIN NORMAL LIMITS. 2507 01:40:55,857 --> 01:40:58,259 SO FOR EXAMPLE, WHAT YOU SEE 2508 01:40:58,259 --> 01:41:00,495 THERE IN PERFORMANCE IQ, THE 2509 01:41:00,495 --> 01:41:03,631 MEASURE OF VISUAL SPATIAL 2510 01:41:03,631 --> 01:41:05,466 SKILLS, THE MEAN IS 100, SO 2511 01:41:05,466 --> 01:41:07,268 ANYTHING IN THE AVERAGE RANGE IS 2512 01:41:07,268 --> 01:41:08,803 90 TO 109, SO THEY'RE SOLIDLY IN 2513 01:41:08,803 --> 01:41:09,904 THE AVERAGE RANGE THERE. 2514 01:41:09,904 --> 01:41:12,340 BUT WE SEE -- AND IF YOU COULD 2515 01:41:12,340 --> 01:41:14,175 ADVANCE ONE MORE SLIDE -- ON THE 2516 01:41:14,175 --> 01:41:17,378 PROCESSING SPEED INDEX, THE 2517 01:41:17,378 --> 01:41:20,414 PATIENTS ARE AT 91, AND THAT'S 2518 01:41:20,414 --> 01:41:21,616 RIGHT AT THE LOWER END OF THE 2519 01:41:21,616 --> 01:41:23,050 AVERAGE RANGE, WHEREAS THE 2520 01:41:23,050 --> 01:41:25,019 SIBLINGS ARE SOLIDLY RIGHT 2521 01:41:25,019 --> 01:41:26,120 THERE, RIGHT AROUND 100. 2522 01:41:26,120 --> 01:41:27,522 AND SO THAT WAS A SIGNIFICANT 2523 01:41:27,522 --> 01:41:27,889 DIFFERENCE. 2524 01:41:27,889 --> 01:41:29,290 SO AGAIN, THEY'RE BOTH IN THE 2525 01:41:29,290 --> 01:41:30,625 AVERAGE RANGE, BUT WE DO SEE 2526 01:41:30,625 --> 01:41:32,360 THAT PATIENTS ARE SCORING 2527 01:41:32,360 --> 01:41:33,461 SIGNIFICANTLY LOWER THAN 2528 01:41:33,461 --> 01:41:39,133 SIBLINGS IN PROCESSING SPEED. 2529 01:41:39,133 --> 01:41:40,368 AND THEN THE QUESTIONNAIRE THAT 2530 01:41:40,368 --> 01:41:43,638 I MENTIONED BEFORE WHERE 2531 01:41:43,638 --> 01:41:44,605 PATIENTS PROVIDE THEIR OWN 2532 01:41:44,605 --> 01:41:46,140 PERCEPTIONS OF THEIR DAY TO DAY 2533 01:41:46,140 --> 01:41:48,810 EXECUTIVE SKILLS CALLED THE 2534 01:41:48,810 --> 01:41:51,045 BRIEF, ALL OF THE SCORES WERE IN 2535 01:41:51,045 --> 01:41:52,380 THE AVERAGE RANGE FOR BOTH 2536 01:41:52,380 --> 01:41:53,614 PATIENTS AND SIBLINGS BUT ALL OF 2537 01:41:53,614 --> 01:41:56,984 THOSE AREAS IN RED ARE WHERE THE 2538 01:41:56,984 --> 01:41:58,319 PATIENT SCORED SIGNIFICANTLY 2539 01:41:58,319 --> 01:41:59,987 HIGHER WHICH IN THIS CASE 2540 01:41:59,987 --> 01:42:02,824 INDICATES MORE SYMPTOMS THAN 2541 01:42:02,824 --> 01:42:10,164 THEIR SIBLING DONORS. 2542 01:42:10,164 --> 01:42:11,566 WE ALSO LOOKED AT THE 2543 01:42:11,566 --> 01:42:12,266 RELATIONSHIP BETWEEN OBJECTIVE 2544 01:42:12,266 --> 01:42:14,001 TEST SCORES AND PAIN, AND WE DID 2545 01:42:14,001 --> 01:42:15,770 NOT SEE ANY RELATIONSHIPS THERE, 2546 01:42:15,770 --> 01:42:16,704 WHICH WAS INTERESTING. 2547 01:42:16,704 --> 01:42:18,372 THAT WAS PAIN IN THE PAST WEEK. 2548 01:42:18,372 --> 01:42:21,342 BUT WE DID SEE THAT HIGHER PAIN 2549 01:42:21,342 --> 01:42:22,410 INTENSITY IN THE PAST WEEK WAS 2550 01:42:22,410 --> 01:42:24,512 RELATED TO MORE PROBLEMS IN 2551 01:42:24,512 --> 01:42:26,781 SEVERAL OF THE SELF-REPORT 2552 01:42:26,781 --> 01:42:27,949 EXECUTIVE FUNCTIONING SUBSCALES 2553 01:42:27,949 --> 01:42:29,016 ON THE BRIEF THAT I JUST SHOWED 2554 01:42:29,016 --> 01:42:35,990 YOU. 2555 01:42:35,990 --> 01:42:37,658 SO NOW LONGITUDALLY IN OUR 2556 01:42:37,658 --> 01:42:40,828 FOLLOW-UP STUDY, WE LOOKED PRE 2557 01:42:40,828 --> 01:42:42,563 AND POST TRANSPLANT, AS I 2558 01:42:42,563 --> 01:42:43,764 MENTIONED, AND WE FOUND THAT 2559 01:42:43,764 --> 01:42:46,100 JUST AMONG THE PATIENTS, THERE 2560 01:42:46,100 --> 01:42:48,502 WAS SIGNIFICANT IMPROVEMENT IN 2561 01:42:48,502 --> 01:42:50,471 PROCESSING SPEED WHERE THEY WENT 2562 01:42:50,471 --> 01:42:52,673 FROM 92 TO 97, SO THEY'RE 2563 01:42:52,673 --> 01:42:55,209 GETTING CLOSER TO THAT MEDIAN OF 2564 01:42:55,209 --> 01:42:56,577 100, MEAN OF 100. 2565 01:42:56,577 --> 01:42:57,879 THAT WAS A SIGNIFICANT 2566 01:42:57,879 --> 01:42:59,180 IMPROVEMENT. 2567 01:42:59,180 --> 01:43:01,482 AND THERE WERE NOT ANY 2568 01:43:01,482 --> 01:43:03,117 IMPROVEMENTS IN THINGS LIKE 2569 01:43:03,117 --> 01:43:07,388 ATTENTION AND MEMORY OR VERBAL 2570 01:43:07,388 --> 01:43:10,358 OR PERFORMANCE IQ. 2571 01:43:10,358 --> 01:43:13,060 WE ALSO LOOKED AT DEPRESSION AND 2572 01:43:13,060 --> 01:43:13,728 ANXIETY. 2573 01:43:13,728 --> 01:43:16,364 THOSE REMAINED STABLE FROM PRE 2574 01:43:16,364 --> 01:43:18,132 TO POST TRANSPLANT, AND THOSE 2575 01:43:18,132 --> 01:43:25,806 WERE ALL WITHIN NORMAL LIMITS. 2576 01:43:25,806 --> 01:43:27,441 THEN THE ONLY AREA IN TERMS OF 2577 01:43:27,441 --> 01:43:28,242 PATIENT-REPORTED OUTCOMES WHERE 2578 01:43:28,242 --> 01:43:32,046 THERE WAS IMPROVEMENT WAS IN THE 2579 01:43:32,046 --> 01:43:36,717 BRIEF SYMPTOM INVENTORY 2580 01:43:36,717 --> 01:43:37,451 SOMATIZATION SUBSCALE, THEY'RE 2581 01:43:37,451 --> 01:43:40,154 NOT REPORTING AS MANY CONCERNS 2582 01:43:40,154 --> 01:43:44,992 WITH PHYSICAL SYMPTOMS. 2583 01:43:44,992 --> 01:43:46,661 BUT WE ALSO FOUND THAT THE 2584 01:43:46,661 --> 01:43:47,728 SIBLINGS IMPROVED IN THEIR 2585 01:43:47,728 --> 01:43:49,030 PROCESSING SPEED FROM BASELINE 2586 01:43:49,030 --> 01:43:50,731 TO 12 MONTHS POST TRANSPLANT, SO 2587 01:43:50,731 --> 01:43:52,934 THERE WAS NOT A SIGNIFICANT 2588 01:43:52,934 --> 01:43:55,536 DIFFERENCE IN THE SLOPES HERE. 2589 01:43:55,536 --> 01:43:57,505 BOTH PATIENTS AND SIBLINGS 2590 01:43:57,505 --> 01:44:00,908 IMPROVED IN PROCESSING SPEED. 2591 01:44:00,908 --> 01:44:02,543 SO WHY DID THAT HAPPEN? 2592 01:44:02,543 --> 01:44:04,612 WE'RE NOT REALLY SURE. 2593 01:44:04,612 --> 01:44:06,580 ONE HYPOTHESIS IS THAT THERE 2594 01:44:06,580 --> 01:44:07,515 WERE PRACTICE EFFECTS. 2595 01:44:07,515 --> 01:44:08,683 SO THE SIBLINGS IMPROVED JUST 2596 01:44:08,683 --> 01:44:12,520 BECAUSE THEY HAD TAKEN THE TEST 2597 01:44:12,520 --> 01:44:13,054 BEFORE. 2598 01:44:13,054 --> 01:44:14,522 WE DON'T USUALLY SEE THAT 2599 01:44:14,522 --> 01:44:16,157 SIGNIFICANT IMPROVEMENT IN 2600 01:44:16,157 --> 01:44:17,124 PROCESSING SPEED IF THEY'VE ONLY 2601 01:44:17,124 --> 01:44:18,893 HAD THE TEST ONCE FROM OVER A 2602 01:44:18,893 --> 01:44:19,994 YEAR APART. 2603 01:44:19,994 --> 01:44:21,662 BUT WE CAN'T RULE THAT OUT AS A 2604 01:44:21,662 --> 01:44:24,598 POSSIBILITY. 2605 01:44:24,598 --> 01:44:26,133 ALSO WHEN THE SIBLINGS CAME IN 2606 01:44:26,133 --> 01:44:28,769 TO DONATE THEIR CELLS, MANY OF 2607 01:44:28,769 --> 01:44:31,172 THEM HAD SOME ANXIETY, NOT 2608 01:44:31,172 --> 01:44:32,073 CLINICALLY SIGNIFICANT BUT MAYBE 2609 01:44:32,073 --> 01:44:33,474 THEY WERE ANXIOUS DURING THE 2610 01:44:33,474 --> 01:44:36,777 TEST SESSION BECAUSE THEY WERE 2611 01:44:36,777 --> 01:44:37,778 CONCERNED ABOUT HOW THE CELL 2612 01:44:37,778 --> 01:44:42,049 DONATION PROCESS WOULD GO, AND 2613 01:44:42,049 --> 01:44:44,018 ALSO WHETHER THEIR SIBLING 2614 01:44:44,018 --> 01:44:46,520 WOULD -- OR THE PATIENT WOULD 2615 01:44:46,520 --> 01:44:48,189 ACTUALLY BE SUCCESSFULLY 2616 01:44:48,189 --> 01:44:53,127 TRANSPLANTED. 2617 01:44:53,127 --> 01:44:55,730 AND IN TERMS OF SOCIAL EMOTIONAL 2618 01:44:55,730 --> 01:44:56,864 FUNCTIONING, ANXIETY AND 2619 01:44:56,864 --> 01:44:57,965 DEPRESSION SCORES WERE WITHIN 2620 01:44:57,965 --> 01:45:00,801 NORMAL LIMITS AND THEY REMAINED 2621 01:45:00,801 --> 01:45:04,305 STABLE PRE TO POST TRANSPLANT. 2622 01:45:04,305 --> 01:45:15,149 WHILE THE SO SE SOMATIZATION SC- 2623 01:45:15,416 --> 01:45:16,884 SO WHAT WE CONCLUDE FROM THAT IS 2624 01:45:16,884 --> 01:45:18,619 THAT PEOPLE WITH SICKLE CELL 2625 01:45:18,619 --> 01:45:20,121 CONSISTENT WITH THE LITERATURE 2626 01:45:20,121 --> 01:45:22,323 DO HAVE A WEAKNESS IN PROCESSING 2627 01:45:22,323 --> 01:45:25,259 SPEED RELATIVE TO OTHER AREAS OF 2628 01:45:25,259 --> 01:45:26,327 FUNCTIONING AND COMPARED TO 2629 01:45:26,327 --> 01:45:26,994 SIBLINGS. 2630 01:45:26,994 --> 01:45:29,663 THE REASONS FOR THAT ARE 2631 01:45:29,663 --> 01:45:31,632 PROBABLY WELL LAID OUT IN THE 2632 01:45:31,632 --> 01:45:33,300 PRIOR TALK JUST BEFORE MINE. 2633 01:45:33,300 --> 01:45:34,602 IMPORTANTLY THERE DON'T SEEM TO 2634 01:45:34,602 --> 01:45:36,570 BE ANY DETRIMENTAL EFFECTS OF 2635 01:45:36,570 --> 01:45:37,872 TRANSPLANT ON COGNITIVE OR 2636 01:45:37,872 --> 01:45:38,439 EMOTIONAL WELL-BEING. 2637 01:45:38,439 --> 01:45:40,107 WE THINK THAT TRANSPLANT MAY 2638 01:45:40,107 --> 01:45:41,442 IMPROVE PROCESSING SPEED, BUT 2639 01:45:41,442 --> 01:45:43,611 FURTHER CONFIRMATION IS NEEDED, 2640 01:45:43,611 --> 01:45:45,613 PARTICULARLY WITH LARGER 2641 01:45:45,613 --> 01:45:45,946 SAMPLES. 2642 01:45:45,946 --> 01:45:50,851 WE HAD A SMALL SAMPLE OF MATCHED 2643 01:45:50,851 --> 01:45:52,620 PATIENTS AND SIBLINGS. 2644 01:45:52,620 --> 01:45:54,188 SO POTENTIALLY WITH LARGER 2645 01:45:54,188 --> 01:45:55,056 SAMPLES WE COULD LEARN MORE 2646 01:45:55,056 --> 01:45:59,760 ABOUT THAT RELATIONSHIP. 2647 01:45:59,760 --> 01:46:02,730 I JUST THANK MY KEY CONTRIBUTORS 2648 01:46:02,730 --> 01:46:03,597 AND THANK YOU FOR YOUR 2649 01:46:03,597 --> 01:46:03,864 ATTENTION. 2650 01:46:03,864 --> 01:46:08,235 [APPLAUSE] 2651 01:46:08,235 --> 01:46:11,505 >> THANK YOU, DR. MARTIN. 2652 01:46:11,505 --> 01:46:13,474 I KNOW WE'RE GETTING READY TO 2653 01:46:13,474 --> 01:46:14,475 END THE SESSION. 2654 01:46:14,475 --> 01:46:15,109 THERE'S SOME QUESTIONS IN THE 2655 01:46:15,109 --> 01:46:15,443 CHAT FOR YOU. 2656 01:46:15,443 --> 01:46:16,243 THANK YOU VERY MUCH. 2657 01:46:16,243 --> 01:46:16,811 MUCH APPRECIATED. 2658 01:46:16,811 --> 01:46:19,647 THANK YOU ALL, THANK YOU ALL FOR 2659 01:46:19,647 --> 01:46:20,031 ATTENDING THIS SYMPOSIUM. 2660 01:46:20,031 --> 01:46:23,768 WE'RE SWITCHING GEARS A LITTLE 2661 01:46:23,768 --> 01:46:28,473 BIT FROM TRANSPLANT TO CURATIVE 2662 01:46:28,473 --> 01:46:29,341 THERAPIES FOR SICKLE CELL, AND 2663 01:46:29,341 --> 01:46:31,776 THIS IS GOING TO REALLY COVER 2664 01:46:31,776 --> 01:46:32,711 THE STATE OF THE ART, WHAT'S 2665 01:46:32,711 --> 01:46:35,914 GOING ON IN THE FIELD OF GENE 2666 01:46:35,914 --> 01:46:38,049 THERAPY AND GENE EDITING, AND SO 2667 01:46:38,049 --> 01:46:42,954 WE WILL HAVE FOUR SEPARATE TALKS 2668 01:46:42,954 --> 01:46:45,924 ON CLONAL HEMATOPOIETIC, 2669 01:46:45,924 --> 01:46:47,225 PRECISION GENE EDITING AND 2670 01:46:47,225 --> 01:46:51,529 PROGRESS AND UPDATES AND ALSO AN 2671 01:46:51,529 --> 01:46:55,467 OVERALL VIEW FROM FYODOR. 2672 01:46:55,467 --> 01:46:57,002 SO LET GET STARTED. 2673 01:46:57,002 --> 01:46:58,937 SO WE WILL HAVE THE FIRST 2674 01:46:58,937 --> 01:47:02,240 SPEAKER, OUR OWN COURTNEY FIT 2675 01:47:02,240 --> 01:47:11,349 THACOURTNEYFITZHUGH FROM NHLBI,G 2676 01:47:11,349 --> 01:47:20,191 ABOUT CLONAL HEMATOPOIESIS 2677 01:47:20,191 --> 01:47:21,059 FOLLOWING CURATIVE THERAPIES FOR 2678 01:47:21,059 --> 01:47:21,726 SICKLE CELL. 2679 01:47:21,726 --> 01:47:25,931 COURTNEY? 2680 01:47:25,931 --> 01:47:26,765 >> GOOD MORNING. 2681 01:47:26,765 --> 01:47:28,533 I'D LIKE TO THANK THE ORGANIZERS 2682 01:47:28,533 --> 01:47:29,868 FOR INVITING ME TO GIVE THIS 2683 01:47:29,868 --> 01:47:31,136 PRESENTATION. 2684 01:47:31,136 --> 01:47:32,704 SO AS YOU ALL KNOW, SICKLE CELL 2685 01:47:32,704 --> 01:47:33,605 DISEASE IS ASSOCIATED WITH 2686 01:47:33,605 --> 01:47:36,207 DAMAGE TO THE BONE MARROW 2687 01:47:36,207 --> 01:47:38,410 MICROENVIRONMENT, HYPOXIA, 2688 01:47:38,410 --> 01:47:39,878 SHORTENED RED CELL SURVIVAL 2689 01:47:39,878 --> 01:47:42,047 WHICH LEADS TO INCREASED 2690 01:47:42,047 --> 01:47:42,914 ERYTHROPOETIC STRESS, 2691 01:47:42,914 --> 01:47:44,149 INFLAMMATION AND OXIDATIVE 2692 01:47:44,149 --> 01:47:47,752 STRESS. 2693 01:47:47,752 --> 01:47:49,120 THERE HAVE BEEN TWO LARGE 2694 01:47:49,120 --> 01:47:50,088 POPULATION STUDIES WHICH HAVE 2695 01:47:50,088 --> 01:47:52,057 SHOWN INCREASED RISK FOR 2696 01:47:52,057 --> 01:47:53,291 AGGRESSIVE MYELOID MALIGNANCIES 2697 01:47:53,291 --> 01:47:53,892 IN PATIENTS WITH SICKLE CELL 2698 01:47:53,892 --> 01:47:54,125 DISEASE. 2699 01:47:54,125 --> 01:47:55,894 THIS STUDY WAS REPORTED BY 2700 01:47:55,894 --> 01:47:57,028 INVESTIGATORS AT U.C. DAVIS, 2701 01:47:57,028 --> 01:48:00,098 WHERE THEY IDENTIFIED OVER 6400 2702 01:48:00,098 --> 01:48:01,199 PATIENTS WITH SICKLE CELL 2703 01:48:01,199 --> 01:48:03,068 DISEASE BETWEEN 1991 AND 2014. 2704 01:48:03,068 --> 01:48:05,337 AND THEY WERE FOLLOWED FOR OVER 2705 01:48:05,337 --> 01:48:06,338 140,000 PERSON-YEARS AND 2706 01:48:06,338 --> 01:48:07,072 COMPARED TO THE GENERAL 2707 01:48:07,072 --> 01:48:08,540 POPULATION. 2708 01:48:08,540 --> 01:48:10,675 THEY DID NOT FIND AN INCREASED 2709 01:48:10,675 --> 01:48:11,943 PREVALENCE OF SOLID TEU NORS, 2710 01:48:11,943 --> 01:48:16,448 TUMORS BUTTHEY DID FIND A 2.3 FD 2711 01:48:16,448 --> 01:48:19,217 INCREASED RISK FOR LEUKEMIA AND 2712 01:48:19,217 --> 01:48:21,086 3.6 FOLD INCREASED RISK FOR 2713 01:48:21,086 --> 01:48:24,322 ACUTE MYELOID LEUKEMIA OR AML. 2714 01:48:24,322 --> 01:48:27,192 THERE ARE MULTIPLE POSSIBLE RISK 2715 01:48:27,192 --> 01:48:28,960 FACTORS FOR MYELOID MALIGNANCY 2716 01:48:28,960 --> 01:48:29,728 DEVELOPMENT IN PATIENTS WITH 2717 01:48:29,728 --> 01:48:31,363 SICKLE CELL DISEASE INCLUDING 2718 01:48:31,363 --> 01:48:32,597 ERYTHROPOETIC STRESS, 2719 01:48:32,597 --> 01:48:35,000 INFLAMMATION, HI HYPOXIA AND 2720 01:48:35,000 --> 01:48:37,135 ACIDOSIS, TRANSFUSION-RELATED 2721 01:48:37,135 --> 01:48:39,637 IMMUNOMODULATION, COMPROMISED 2722 01:48:39,637 --> 01:48:40,872 APOPTOSIS, ENDOTHELIAL DAMAGE, 2723 01:48:40,872 --> 01:48:43,641 INCREASED AGE, AND CLONAL 2724 01:48:43,641 --> 01:48:47,912 HEMATOPOEISIS. 2725 01:48:47,912 --> 01:48:51,516 NON-MYELOABLATIVE HLA MATCHED 2726 01:48:51,516 --> 01:48:54,619 SIBLING TRANSPLANT -- THE 2727 01:48:54,619 --> 01:48:59,324 ORIGINAL PROTOCOL WHERE PATIENTS 2728 01:48:59,324 --> 01:49:04,129 RECEIVE AL EMTEUZ MAN -- 2729 01:49:04,129 --> 01:49:05,830 ORIGINAL GOAL WOS A MIXTURE OF 2730 01:49:05,830 --> 01:49:07,265 DONOR RECIPIENT CELLS BECAUSE WE 2731 01:49:07,265 --> 01:49:09,100 WERE MOST CONCERNED AT THE TIME 2732 01:49:09,100 --> 01:49:11,302 FOR GRAFT-VERSUS-HOST DISEASE. 2733 01:49:11,302 --> 01:49:13,471 INVESTIGATORS AT THE NIH 2734 01:49:13,471 --> 01:49:14,272 UNIVERSITY OF ILLINOIS CHICAGO 2735 01:49:14,272 --> 01:49:16,474 AND RIYADH, SAUDI ARABIA 2736 01:49:16,474 --> 01:49:18,343 RECENTLY REPORTED 122 PATIENTS 2737 01:49:18,343 --> 01:49:20,545 WHO UNDERWENT THIS TRANSPLANT 2738 01:49:20,545 --> 01:49:21,312 WITH THIS REGIMEN. 2739 01:49:21,312 --> 01:49:23,281 THE MEDIAN FOLLOW-UP WAS FOUR 2740 01:49:23,281 --> 01:49:24,849 YEARS AND AT FIVE YEARS POST 2741 01:49:24,849 --> 01:49:26,284 TRANSPLANT, THE OVERALL SURVIVAL 2742 01:49:26,284 --> 01:49:29,120 IS 93%, THE EVENT-FREE SURVIVAL 2743 01:49:29,120 --> 01:49:30,989 WAS 85%. 2744 01:49:30,989 --> 01:49:32,657 NONE OF THE PATIENTS DEVELOPED 2745 01:49:32,657 --> 01:49:34,793 GRADE 3 TO 4 ACUTE GVHD, AND NO 2746 01:49:34,793 --> 01:49:37,695 ONE DEVELOPED CHRONIC GVHD. 2747 01:49:37,695 --> 01:49:39,264 UNFORTUNATELY, LESS THAN 15% OF 2748 01:49:39,264 --> 01:49:40,698 PATIENTS WITH SICKLE CELL 2749 01:49:40,698 --> 01:49:42,667 DISEASE HAVE HLA MATCHED SIBLING 2750 01:49:42,667 --> 01:49:44,302 DONORS. 2751 01:49:44,302 --> 01:49:47,072 SO THIS IS OUR ORIGINAL 2752 01:49:47,072 --> 01:49:47,972 HAPLOIDENTICAL TRANSPLANT STUDY 2753 01:49:47,972 --> 01:49:50,041 WHICH WAS WRITTEN AS A DOSE 2754 01:49:50,041 --> 01:49:54,879 ESCALATION OF POST TRANSPLANT 2755 01:49:54,879 --> 01:50:01,986 CYCCYCLO -- ALL THE PATIENTS 2756 01:50:01,986 --> 01:50:04,622 RECEIVED SIROLIMUS. 2757 01:50:04,622 --> 01:50:06,724 THE FIRST COHORT DID NOT RECEIVE 2758 01:50:06,724 --> 01:50:07,692 ANY CYCLOPHOSPHAMIDE. 2759 01:50:07,692 --> 01:50:09,360 THE SECOND COHOARD RECEIVED ONE 2760 01:50:09,360 --> 01:50:13,198 DOSE AND THE THIRD COHORT 2761 01:50:13,198 --> 01:50:16,501 RECEIVED 100MGS PER KG IN 2762 01:50:16,501 --> 01:50:17,702 DIVIDED DOSES. 2763 01:50:17,702 --> 01:50:20,805 IF TOO MANY PATIENTS DEVELOPED 2764 01:50:20,805 --> 01:50:22,107 GRAFT REJECTION OR MODERATE TO 2765 01:50:22,107 --> 01:50:25,276 SE VESEVERE GVHD, WE WOULD MOVEO 2766 01:50:25,276 --> 01:50:26,111 THE NEXT COHORT. 2767 01:50:26,111 --> 01:50:27,445 THESE ARE THE RESULTS OF THE 2768 01:50:27,445 --> 01:50:28,079 STUDY. 2769 01:50:28,079 --> 01:50:29,380 22 PATIENTS WERE TRANSPLANTED. 2770 01:50:29,380 --> 01:50:32,016 YOU CAN SEE IN THE LAST TWO 2771 01:50:32,016 --> 01:50:33,051 COLUMBUS THAT THE SICKLE CELL 2772 01:50:33,051 --> 01:50:34,586 DISEASE-FREE SURVIVAL IMPROVED 2773 01:50:34,586 --> 01:50:36,754 WITH THE ADDITION OF POST 2774 01:50:36,754 --> 01:50:38,089 TRANSPLANT CYCLOPHOSPHAMIDE FROM 2775 01:50:38,089 --> 01:50:41,092 0% IN THE FIRST COHORT TO 50% IN 2776 01:50:41,092 --> 01:50:42,193 THE THIRD COHORT. 2777 01:50:42,193 --> 01:50:45,396 SO WHILE THERE WAS AN 2778 01:50:45,396 --> 01:50:47,031 IMPROVEMENT IN THE GRAFT 2779 01:50:47,031 --> 01:50:48,867 REJECTION RATE, THE GRAFT 2780 01:50:48,867 --> 01:50:51,102 REJECTION RATE WAS UNACCEPTABLY 2781 01:50:51,102 --> 01:50:52,203 HIGH AND THE STUDY CLOSED TO 2782 01:50:52,203 --> 01:50:53,071 ACCRUAL. 2783 01:50:53,071 --> 01:50:55,273 BECAUSE OF THE HIGHER RATES OF 2784 01:50:55,273 --> 01:50:56,708 GRAFT-VERSUS-HOST DISEASE, 2785 01:50:56,708 --> 01:50:58,576 ESPECIALLY IN THE HAPLOIDENTICAL 2786 01:50:58,576 --> 01:51:01,212 SET, WE HAVE TWO NEWER PROTOCOLS 2787 01:51:01,212 --> 01:51:07,185 BOTH WHICH INCLUDE INTRAVENOUS 2788 01:51:07,185 --> 01:51:09,354 PENTOSTATIN AND DAILY ORAL 2789 01:51:09,354 --> 01:51:11,222 CYCLOPHOSPHAMIDE AND TO DATE, 2790 01:51:11,222 --> 01:51:13,458 BOTH STUDIES ARE ASSOCIATED WITH 2791 01:51:13,458 --> 01:51:15,760 DECREASED INCIDENCE OF GRAFT 2792 01:51:15,760 --> 01:51:16,027 REJECTION. 2793 01:51:16,027 --> 01:51:19,130 NEXT I WANT TO INTRODUCE A 2794 01:51:19,130 --> 01:51:25,103 LITTLE ABO ABOUT THE BLUEBIRD B. 2795 01:51:25,103 --> 01:51:26,538 THE PATIENTS WERE DIVIDED INTO 2796 01:51:26,538 --> 01:51:28,806 THREE DIFFERENT COHORTS. 2797 01:51:28,806 --> 01:51:30,008 PRECOLLECTION RED CELL 2798 01:51:30,008 --> 01:51:31,609 TRANSFUSION REGIMEN WAS OPTIONAL 2799 01:51:31,609 --> 01:51:33,111 IN GROUP A PATIENTS BUT IS 2800 01:51:33,111 --> 01:51:34,345 REQUIRED IN GROUPS B AND C 2801 01:51:34,345 --> 01:51:35,213 PATIENTS. 2802 01:51:35,213 --> 01:51:36,548 THE HEMATOPOIETIC STEM CELL 2803 01:51:36,548 --> 01:51:40,018 SOURCE WAS BONE MAR BONE MAYOR N 2804 01:51:40,018 --> 01:51:41,920 A AND B PATIENTS AND 2805 01:51:41,920 --> 01:51:42,854 PERIPHERALLIZED BLOOD IN GROUP C 2806 01:51:42,854 --> 01:51:43,288 PATIENTS. 2807 01:51:43,288 --> 01:51:44,822 THE ORIGINAL DRUG PRODUCT 2808 01:51:44,822 --> 01:51:45,790 MANUFACTURING PROCESS WAS USED 2809 01:51:45,790 --> 01:51:47,926 IN GROUP A AND SOME GROUP B 2810 01:51:47,926 --> 01:51:49,027 PATIENTS AND A MORE REFINED 2811 01:51:49,027 --> 01:51:50,461 PROCESS FOR THE REST OF GROUP B 2812 01:51:50,461 --> 01:51:52,197 AND ALL OF GROUP C PATIENTS. 2813 01:51:52,197 --> 01:51:54,199 AND WITH THESE CHANGES, THERE 2814 01:51:54,199 --> 01:51:55,733 WAS A HIGHER VECTOR COPY NUMBER, 2815 01:51:55,733 --> 01:51:58,303 A HIGHER CELL DOSE, AND SIGHER 2816 01:51:58,303 --> 01:51:59,604 EFFICACY IN GROUP C COMPARED TO 2817 01:51:59,604 --> 01:52:00,572 GROUP A PATIENTS. 2818 01:52:00,572 --> 01:52:01,739 AND IMPORTANTLY ALL OF THE 2819 01:52:01,739 --> 01:52:04,676 PATIENTS RECEIVED MYELOABLATIVE 2820 01:52:04,676 --> 01:52:08,947 CONDITIONING WITH BUSULFAN. 2821 01:52:08,947 --> 01:52:11,716 UNFORTUNATELY, WE RECENTLY 2822 01:52:11,716 --> 01:52:13,785 REPORTED THAT FIVE OF 120 2823 01:52:13,785 --> 01:52:15,887 PATIENTS WE TRANSPLANTED 2824 01:52:15,887 --> 01:52:18,823 DEVELOPED EITHER MYELODYSPLASTIC 2825 01:52:18,823 --> 01:52:22,327 SYNDROME OR MDN, ALL HAD 2826 01:52:22,327 --> 01:52:23,394 HOMOZYGOUS SICKLE CELL DISEASE 2827 01:52:23,394 --> 01:52:25,330 WITH AGES RANGING FROM 20 TO 44 2828 01:52:25,330 --> 01:52:26,331 YEARS. 2829 01:52:26,331 --> 01:52:28,399 TWO OF THE PATIENTS -- SIBLING 2830 01:52:28,399 --> 01:52:29,834 TRANSPLANT. 2831 01:52:29,834 --> 01:52:32,170 THE REMAINED DER HAPLOIDENTICAL 2832 01:52:32,170 --> 01:52:34,038 TRANSPLANT. 2833 01:52:34,038 --> 01:52:38,776 1 2834 01:52:40,979 --> 01:52:44,148 TWO OF THE PATIENTS HAD MDS, THE 2835 01:52:44,148 --> 01:52:45,550 REMAINING THREE AML THAT WAS 2836 01:52:45,550 --> 01:52:47,218 DIAGNOSED BETWEEN FOUR MONTHS 2837 01:52:47,218 --> 01:52:49,654 AND 5 1/2 YEARS POST TRANSPLANT. 2838 01:52:49,654 --> 01:52:51,322 FOUR OF THE PATIENTS COMPLETELY 2839 01:52:51,322 --> 01:52:51,923 REJECTED THEIR GRAFTS. 2840 01:52:51,923 --> 01:52:54,025 ONE OF THEM HAD IMPENDING GRAFT 2841 01:52:54,025 --> 01:52:56,594 FAILURE WITH THE DONOR MYELOID 2842 01:52:56,594 --> 01:52:59,864 CHIMERISM OF 16% AND A DONOR -- 2843 01:52:59,864 --> 01:53:00,999 18% AT DIAGNOSIS. 2844 01:53:00,999 --> 01:53:02,333 AND ALL FIVE PATIENTS ARE 2845 01:53:02,333 --> 01:53:05,937 DECEASED. 2846 01:53:05,937 --> 01:53:07,505 THIS TABLE SHOWS THE INCIDENCE 2847 01:53:07,505 --> 01:53:11,909 RATE OF AGGRESSIVE MYELOID 2848 01:53:11,909 --> 01:53:13,144 MALIGNANCIES ACROSS STUDIES. 2849 01:53:13,144 --> 01:53:14,479 THE FIRST THREE COLUMBUS INCLUDE 2850 01:53:14,479 --> 01:53:16,581 PATIENTS WHO UNDERWENT HLA 2851 01:53:16,581 --> 01:53:17,782 MATCHED SIBLING TRANSPLANT. 2852 01:53:17,782 --> 01:53:19,217 THE FIRST TWO COLUMBUS THE 2853 01:53:19,217 --> 01:53:25,056 PATIENTS ONLY RECEIVED 2854 01:53:25,056 --> 01:53:26,791 ALEMTUZUMAB. 2855 01:53:26,791 --> 01:53:28,326 FROM 87-POINT A TO 518 PERSON 2856 01:53:28,326 --> 01:53:30,595 YEARS IN THE INCIDENCE OF MDS OR 2857 01:53:30,595 --> 01:53:33,965 AML RANGED FROM ZERO TO 0.8 PER 2858 01:53:33,965 --> 01:53:38,770 100 PERSON YEARS. 2859 01:53:38,770 --> 01:53:40,038 WHEN THE PRECONDITIONING WAS 2860 01:53:40,038 --> 01:53:42,407 ADDED, AT RISK TIME IS 96 PERSON 2861 01:53:42,407 --> 01:53:45,043 YEARS AND THE INCIDENCE OF MDS 2862 01:53:45,043 --> 01:53:47,078 OR AML IS 1.04. 2863 01:53:47,078 --> 01:53:48,646 THESE NEXT TWO COLUMBUS SHOW 2864 01:53:48,646 --> 01:53:50,248 PATIENTS WHO UNDERWENT 2865 01:53:50,248 --> 01:53:50,848 HAPLOIDENTICAL TRANSPLANT. 2866 01:53:50,848 --> 01:53:52,517 THIS COLUMN SHOWS THE PATIENTS 2867 01:53:52,517 --> 01:53:56,521 WHO WERE ENROLLED I IN A STUDY - 2868 01:53:56,521 --> 01:53:59,090 WITH AT RISK TIME OF 176 PERSON 2869 01:53:59,090 --> 01:54:01,392 YEARS, THE INCIDENCE OF MDS OR 2870 01:54:01,392 --> 01:54:04,629 AML IS 1.7 PER 100 PERSON YEARS. 2871 01:54:04,629 --> 01:54:06,931 AND WITH AT RISK TIME OF JUST 2872 01:54:06,931 --> 01:54:07,799 UNDER 50 PERSON YEARS, WE DID 2873 01:54:07,799 --> 01:54:10,168 NOT HAVE ANYBODY DEVELOP MDS OR 2874 01:54:10,168 --> 01:54:12,003 AML. 2875 01:54:12,003 --> 01:54:14,639 THE THERAPEUTIC GOAL FOR THESE 2876 01:54:14,639 --> 01:54:15,840 STUDIES AS I MENTIONED EARLIER 2877 01:54:15,840 --> 01:54:17,508 IS MIXED CHIMERISM. 2878 01:54:17,508 --> 01:54:19,477 I'D LIKE TO THANK BLUEBIRD BIO 2879 01:54:19,477 --> 01:54:22,547 FOR PROVIDING DATA ON THE NUMBER 2880 01:54:22,547 --> 01:54:24,115 OF PATIENTS IN PERSON YEARS, AND 2881 01:54:24,115 --> 01:54:27,051 YOU CAN SEE WITH AT RISK TIME OF 2882 01:54:27,051 --> 01:54:28,519 112 PERSON YEARS, THE INCIDENCE 2883 01:54:28,519 --> 01:54:30,521 OF MDS OR AML WAS SIMILAR TO 2884 01:54:30,521 --> 01:54:32,056 WHAT WE SAW ON TWO OF OUR 2885 01:54:32,056 --> 01:54:33,958 STUDIES. 2886 01:54:33,958 --> 01:54:34,726 IMPORTANTLY, MOST OF THESE 2887 01:54:34,726 --> 01:54:36,027 PATIENTS WERE ENROLLED IN GROUP 2888 01:54:36,027 --> 01:54:36,594 A. 2889 01:54:36,594 --> 01:54:38,429 THIS COMPARES TO TWO LARGER 2890 01:54:38,429 --> 01:54:40,264 STUDIES THAT INCLUDED MOSTLY 2891 01:54:40,264 --> 01:54:41,566 PEDIATRIC PATIENTS AND WHERE 2892 01:54:41,566 --> 01:54:43,768 MOST OF THEM UNDERWENT 2893 01:54:43,768 --> 01:54:45,470 MYELOABLATIVE HLA MATCHED 2894 01:54:45,470 --> 01:54:45,903 SIBLING TRANSPLANT. 2895 01:54:45,903 --> 01:54:47,238 YOU CAN SEE WITH AT RISK TIME 2896 01:54:47,238 --> 01:54:49,273 RANGING FROM 1600 TO 1800 PERSON 2897 01:54:49,273 --> 01:54:51,476 YEARS, NO ONE DEVELOPED MDS OR 2898 01:54:51,476 --> 01:54:53,244 AML, AND WITH BOTH STUDIES, THE 2899 01:54:53,244 --> 01:54:57,882 GOAL WAS FULL DONOR CHIMERISM. 2900 01:54:57,882 --> 01:54:59,317 AND I JUST -- SINCE THAT STUDY 2901 01:54:59,317 --> 01:55:01,285 WAS REPORTED TWO YEARS AGO, I'M 2902 01:55:01,285 --> 01:55:02,553 SHOWING HERE THE UPDATED 2903 01:55:02,553 --> 01:55:04,622 INCIDENCE RATE OF MDS OR AML AND 2904 01:55:04,622 --> 01:55:05,790 I'M THANKFUL TO REPORT WE HAVE 2905 01:55:05,790 --> 01:55:08,393 NOT HAD ANYONE DEVELOP MDS OR 2906 01:55:08,393 --> 01:55:13,297 AML IN THE LAST TWO YEARS. 2907 01:55:13,297 --> 01:55:16,200 SO I MENTIONED EARLIER THE STUDY 2908 01:55:16,200 --> 01:55:19,103 FROM U.C. DAVIS AND THAT OVER 2909 01:55:19,103 --> 01:55:19,737 6400 PATIENTS WITH SICKLE CELL 2910 01:55:19,737 --> 01:55:20,905 DISEASE WERE FOLLOWED FOR OVER 2911 01:55:20,905 --> 01:55:22,407 27 YEARS. 2912 01:55:22,407 --> 01:55:23,541 DURING THAT TIME, ONLY SIX 2913 01:55:23,541 --> 01:55:27,879 PATIENTS DEVELOPED AML, OVER 2914 01:55:27,879 --> 01:55:30,681 140,000 PERSON YEARS, OR 0.004 2915 01:55:30,681 --> 01:55:32,083 PER 100 PERSON YEARS. 2916 01:55:32,083 --> 01:55:34,619 DURING THAT SAME TIME, 1.67 2917 01:55:34,619 --> 01:55:35,553 INDIVIDUALS WITHOUT SICKLE CELL 2918 01:55:35,553 --> 01:55:37,588 DISEASE WERE EXPECTED TO DEVELOP 2919 01:55:37,588 --> 01:55:38,923 AML WHEN CONTROLLED FOR AGE, 2920 01:55:38,923 --> 01:55:43,194 SEX, RACE, AND ETHNICITY, OR 2921 01:55:43,194 --> 01:55:44,896 0.001 PER 100 PERSON YEARS. 2922 01:55:44,896 --> 01:55:46,864 SO WHILE THERE'S AN INCREASE 2923 01:55:46,864 --> 01:55:48,132 RELATIVE RISK OF LEUKEMIA 2924 01:55:48,132 --> 01:55:50,001 DEVELOPMENT IN PATIENTS WITH 2925 01:55:50,001 --> 01:55:50,568 SICKLE CELL DISEASE, THE 2926 01:55:50,568 --> 01:55:54,472 ABSOLUTE RISK IS LOW. 2927 01:55:54,472 --> 01:55:55,940 THIS COMPARES TO THREE OF OUR 2928 01:55:55,940 --> 01:55:58,676 PATIENTS DEVELOPING AML OVER 844 2929 01:55:58,676 --> 01:56:01,779 PERSON YEARS, OR 0.36 PER 100 2930 01:56:01,779 --> 01:56:04,449 PERSON YEARS. 2931 01:56:04,449 --> 01:56:06,717 SO THE RATE OF AML IS 2932 01:56:06,717 --> 01:56:08,019 APPROXIMATELY 89 TIMES HIGHER IN 2933 01:56:08,019 --> 01:56:10,254 ADULTS FOLLOWING TRANSPLANT FOR 2934 01:56:10,254 --> 01:56:11,456 SICKLE CELL DISEASE RESULTING IN 2935 01:56:11,456 --> 01:56:13,324 GRAFT FAILURE COMPARED TO THOSE 2936 01:56:13,324 --> 01:56:14,392 WITH SICKLE CELL DISEASE WHO DO 2937 01:56:14,392 --> 01:56:18,262 NOT RECEIVE CURATIVE THERAPY. 2938 01:56:18,262 --> 01:56:21,699 WHY IS THE IP INCIDENCE OF 2939 01:56:21,699 --> 01:56:23,134 AGGRESSIVE MYELOID MALIGNANCIES 2940 01:56:23,134 --> 01:56:24,836 HIGHER IN ADULTS AFTER GRAFT 2941 01:56:24,836 --> 01:56:25,670 FAILURE AND GENE THERAPY FOR 2942 01:56:25,670 --> 01:56:27,171 SICKLE CELL DISEASE? 2943 01:56:27,171 --> 01:56:28,773 THERE ARE MULTIPLE POSSIBLE 2944 01:56:28,773 --> 01:56:31,175 REASONS THAT NEED FURTHER 2945 01:56:31,175 --> 01:56:31,676 EXPLORATION. 2946 01:56:31,676 --> 01:56:35,980 THIS STUDY FROM U.S. DAVIS 2947 01:56:35,980 --> 01:56:36,747 INVESTIGATORS SHOW PATIENTS WHO 2948 01:56:36,747 --> 01:56:38,249 ARE OLDER AND THOSE WITH MORE 2949 01:56:38,249 --> 01:56:39,650 SEVERE DISEASE HAD HIGHER RISK 2950 01:56:39,650 --> 01:56:40,485 OF LEUKEMIA. 2951 01:56:40,485 --> 01:56:41,586 WE TRANSPLANT PATIENTS THAT ARE 2952 01:56:41,586 --> 01:56:43,621 OLDER THAN TYPICAL AND WITH MORE 2953 01:56:43,621 --> 01:56:45,022 SEVERE DISEASE THAN TYPICAL. 2954 01:56:45,022 --> 01:56:46,491 WE ALSO HAVE A LONGER DURATION 2955 01:56:46,491 --> 01:56:48,092 OF FOLLOW-UP AND A HIGHER 2956 01:56:48,092 --> 01:56:50,061 PROPORTION OF OUR PATIENTS ARE 2957 01:56:50,061 --> 01:56:50,728 FOLLOWED LONG TERM. 2958 01:56:50,728 --> 01:56:52,363 COMPARED TO THE PEDIATRIC 2959 01:56:52,363 --> 01:56:54,832 SETTING, WE ALSO USE TBI BASED 2960 01:56:54,832 --> 01:56:56,501 CONDITIONING VERSUS CHEMOTHERAPY 2961 01:56:56,501 --> 01:56:58,536 BASED CONDITIONING, AND BOTH 2962 01:56:58,536 --> 01:57:00,505 WITH OUR APPROACH AT THE NIH AND 2963 01:57:00,505 --> 01:57:02,540 WITH GENE THERAPY, THERE'S A 2964 01:57:02,540 --> 01:57:06,477 REQUIREMENT OF REGENERATIVE 2965 01:57:06,477 --> 01:57:09,013 HEMATOPOEISIS. 2966 01:57:09,013 --> 01:57:11,749 SO WE'VE HAD OF FIVE PATIENTS I 2967 01:57:11,749 --> 01:57:14,519 TOLD YOU DEVELOPED MDS OR AML, 2968 01:57:14,519 --> 01:57:16,187 FOUR OF THEM HAD NEXT GENERATION 2969 01:57:16,187 --> 01:57:18,022 SEQUENCING DONE AT THE TIME OF 2970 01:57:18,022 --> 01:57:20,458 AML OR MDS DIAGNOSIS, AND ALL 2971 01:57:20,458 --> 01:57:22,727 FOUR HAD DIFFERENT PATHOGENIC 2972 01:57:22,727 --> 01:57:23,628 TP53 MUTATIONS. 2973 01:57:23,628 --> 01:57:25,963 SO IN THIS FIRST PATIENT, YOU 2974 01:57:25,963 --> 01:57:29,667 CAN SEE AT THE TIME OF 2975 01:57:29,667 --> 01:57:32,503 DIAGNOSIS, HE HAD A TP53 2976 01:57:32,503 --> 01:57:34,639 MUTATION PRESENT WITH FREQUENCY 2977 01:57:34,639 --> 01:57:35,306 OF 24%. 2978 01:57:35,306 --> 01:57:38,276 WHEN WE WENT BACK TO THE SAMPLE 2979 01:57:38,276 --> 01:57:40,011 THAT WE HAD COLLECTED BEFORE 2980 01:57:40,011 --> 01:57:41,078 TRANSPLANT OR EVEN BEFORE 2981 01:57:41,078 --> 01:57:43,581 CONDITIONING, THE SAME MUTATION 2982 01:57:43,581 --> 01:57:48,519 WAS PRESENT AT A VERY LOW 2983 01:57:48,519 --> 01:57:49,153 FREQUENCY. 2984 01:57:49,153 --> 01:57:49,987 SIMILARLY IN THE NEXT TWO 2985 01:57:49,987 --> 01:57:52,323 PATIENTS WHO HAD EITHER MDS OR 2986 01:57:52,323 --> 01:57:54,292 AML, THE TP53 MUTATION AT THE 2987 01:57:54,292 --> 01:57:56,727 TIME OF DIAGNOSIS RANGED FROM 2988 01:57:56,727 --> 01:57:59,363 2.9% TO 508%, AND THESE SAME 2989 01:57:59,363 --> 01:58:00,565 MUTATIONS WERE ALSO FOUND AT 2990 01:58:00,565 --> 01:58:04,535 BASELINE RANGING FROM 0.06 TO 2991 01:58:04,535 --> 01:58:06,270 0.36%. 2992 01:58:06,270 --> 01:58:07,405 THIS FOURTH PATIENT DEVELOPED 2993 01:58:07,405 --> 01:58:09,307 AML AT 5 1/2 YEARS POST 2994 01:58:09,307 --> 01:58:10,308 TRANSPLANT, AND SHE WAS FOUND TO 2995 01:58:10,308 --> 01:58:14,579 HAVE A TP53 MUTATION WITH 2996 01:58:14,579 --> 01:58:16,147 FREQUENCY OF 78.8%. 2997 01:58:16,147 --> 01:58:18,215 WE DID NOT DETECT MUTATION AT 2998 01:58:18,215 --> 01:58:19,850 BASELINE OR EVEN AT 1 1/2 YEARS 2999 01:58:19,850 --> 01:58:20,851 POST TRANSPLANT. 3000 01:58:20,851 --> 01:58:22,219 WE FIRST DETECTED IT AT FOUR 3001 01:58:22,219 --> 01:58:27,425 YEARS POST TRANSPLANT AT 0.06%. 3002 01:58:27,425 --> 01:58:32,396 ONE YEAR LATER IT INCREASED TO 3003 01:58:32,396 --> 01:58:34,732 0.34% AND NEXT YEAR IT REELIN 3004 01:58:34,732 --> 01:58:35,766 CREASED TO 79%. 3005 01:58:35,766 --> 01:58:37,134 SO IT WAS NOT PRESENT AT 3006 01:58:37,134 --> 01:58:38,569 BASELINE OR WE JUST WEREN'T ABLE 3007 01:58:38,569 --> 01:58:40,571 TO DETECT IT. 3008 01:58:40,571 --> 01:58:42,940 SO WE WANTED TO KNOW IN OUR 3009 01:58:42,940 --> 01:58:44,642 PATIENTS WHO HAVE NOT DEVELOPED 3010 01:58:44,642 --> 01:58:47,945 MDS OR AML WHETHER THEY HAD TP53 3011 01:58:47,945 --> 01:58:48,879 MUTATIONS PRESENT AT BASELINE. 3012 01:58:48,879 --> 01:58:51,382 SO YOU CAN SEE HERE IN SEVEN 3013 01:58:51,382 --> 01:58:52,683 PATIENTS WHO DEVELOPED GRAFT 3014 01:58:52,683 --> 01:58:54,218 FAILURE BUT WITHOUT LEUKEMIA, 3015 01:58:54,218 --> 01:58:57,021 NONE OF THEM HAD TP53 MUTATIONS 3016 01:58:57,021 --> 01:58:58,422 AT BASELINE WITH FOLLOW-UP 3017 01:58:58,422 --> 01:59:00,257 RANGING FROM 4 1/2 TO 12 YEARS 3018 01:59:00,257 --> 01:59:03,694 POST TRANSPLANT. 3019 01:59:03,694 --> 01:59:05,630 AND THESE ARE EIGHT ENGRAFTED 3020 01:59:05,630 --> 01:59:07,465 PATIENTS WHO ALSO DID NOT 3021 01:59:07,465 --> 01:59:09,634 DEVELOP MDS OR AML, AND AGAIN, 3022 01:59:09,634 --> 01:59:11,702 NONE OF THEM WERE FOUND TO HAVE 3023 01:59:11,702 --> 01:59:13,871 TP53 MUTATIONS AT BASELINE WITH 3024 01:59:13,871 --> 01:59:17,708 FOLLOW-UP RANGING FROM FOUR TO 3025 01:59:17,708 --> 01:59:19,744 EIGHT YEARS. 3026 01:59:19,744 --> 01:59:21,278 SO I'M WORKING WITH 3027 01:59:21,278 --> 01:59:22,446 COLLABORATORS AT MULTIPLE 3028 01:59:22,446 --> 01:59:25,216 INSTITUTIONS INCLUDING HOCH KINS 3029 01:59:25,216 --> 01:59:26,550 AND VANDERBILT, IT'S CALLED 3030 01:59:26,550 --> 01:59:27,351 COALESCE. 3031 01:59:27,351 --> 01:59:29,253 IN OUR HYPOTHESIS, AFTER GRAFT 3032 01:59:29,253 --> 01:59:32,023 FAILURE OR GENE THERAPY, THE 3033 01:59:32,023 --> 01:59:35,226 STRESS IS SWITCHING BY 3034 01:59:35,226 --> 01:59:38,596 AUTOLOGOUS CELLS, DRIVES CLONAL 3035 01:59:38,596 --> 01:59:41,232 EXPANSION AND -- PRE-EXISTING 3036 01:59:41,232 --> 01:59:42,099 PREMALIGNANT CLONES EVENTUALLY 3037 01:59:42,099 --> 01:59:45,336 RESULTING IN AML OR MDS. 3038 01:59:45,336 --> 01:59:47,738 SO THIS SHOWS A THEORETICAL 3039 01:59:47,738 --> 01:59:49,440 MODEL FOR MYELOID MALIGNANCY 3040 01:59:49,440 --> 01:59:50,107 DEVELOPMENT AFTER CURATIVE 3041 01:59:50,107 --> 01:59:51,042 THERAPIES FOR SICKLE CELL 3042 01:59:51,042 --> 01:59:52,276 DISEASE AND HOW TO MITIGATE THE 3043 01:59:52,276 --> 01:59:53,711 RISK. 3044 01:59:53,711 --> 01:59:55,546 SO THIS RED CELL REPRESENTS A 3045 01:59:55,546 --> 01:59:57,682 STEM CELL OF A PATIENT WITH 3046 01:59:57,682 --> 01:59:59,417 SICKLE CELL DISEASE, AND DUE TO 3047 01:59:59,417 --> 02:00:01,218 AGING AND COMORBIDITIES, THE 3048 02:00:01,218 --> 02:00:02,920 PATIENTS MAY DEVELOP LOW LEVEL 3049 02:00:02,920 --> 02:00:04,588 SOMATIC MUTATIONS THAT, OVER 3050 02:00:04,588 --> 02:00:06,223 TIME, DO NOT EXPAND IN THE 3051 02:00:06,223 --> 02:00:07,858 ABSENCE OF CURATIVE THERAPY SO 3052 02:00:07,858 --> 02:00:09,460 THAT MOST PATIENTS WITH SICKLE 3053 02:00:09,460 --> 02:00:10,995 CELL DISEASE DO NOT DEVELOP 3054 02:00:10,995 --> 02:00:13,864 MYELOID MALIGNANCIES. 3055 02:00:13,864 --> 02:00:15,466 IF THE PATIENT HAS A SOMATIC 3056 02:00:15,466 --> 02:00:17,501 MUTATION AND THEN UNDERGOES 3057 02:00:17,501 --> 02:00:19,070 GRAFT REJECTION OR GENE THERAPY, 3058 02:00:19,070 --> 02:00:22,206 BOTH REQUIRING AUTOLOGOUS 3059 02:00:22,206 --> 02:00:24,341 RECONSTITUTION, THE CLONE CAN 3060 02:00:24,341 --> 02:00:25,009 EXPAND AND THE PATIENT CAN 3061 02:00:25,009 --> 02:00:26,410 DEVELOP A MYELOID MALIGNANCY, 3062 02:00:26,410 --> 02:00:27,611 AND IT'S POSSIBLE THE REASON WE 3063 02:00:27,611 --> 02:00:29,413 SAW THIS IN GROUP A PATIENTS IS 3064 02:00:29,413 --> 02:00:31,015 THAT THERE WAS A LOWER CELL DOSE 3065 02:00:31,015 --> 02:00:34,418 AND THERE MIGHT BE EVEN MORE 3066 02:00:34,418 --> 02:00:35,052 ERYTHROPOETIC PROLIFERATION 3067 02:00:35,052 --> 02:00:37,655 THAT'S NEEDED. 3068 02:00:37,655 --> 02:00:38,656 >> SPEAKER, 2 MINUTES LEFT. 3069 02:00:38,656 --> 02:00:39,190 >> OKAY. 3070 02:00:39,190 --> 02:00:40,624 IF THE PATIENT WAS FOUND TO HAVE 3071 02:00:40,624 --> 02:00:43,761 A GENETIC RISK FACTOR, WE WOULD 3072 02:00:43,761 --> 02:00:44,862 RECOMMEND AL JE NATION 3073 02:00:44,862 --> 02:00:46,163 TRANSPLANTATION WITH FULL DONOR 3074 02:00:46,163 --> 02:00:48,532 KIESM RISM, DONOR DERIVED 3075 02:00:48,532 --> 02:00:50,034 LEUKEMIA IS EXCEEDINGLY RARE IN 3076 02:00:50,034 --> 02:00:51,602 SICKLE CELL DISEASE WHEN DONORS 3077 02:00:51,602 --> 02:00:53,237 ARE YOUNGER AND NOT EXPECTED TO 3078 02:00:53,237 --> 02:00:59,543 HAVE CLONAL HEMATOPOEISIS. 3079 02:00:59,543 --> 02:01:01,412 UNFORTUNATELY -- THIS IS AN 3080 02:01:01,412 --> 02:01:03,214 ACTIVE AREA OF RESEARCH IN MY 3081 02:01:03,214 --> 02:01:05,983 LAB AND OUTSIDE. 3082 02:01:05,983 --> 02:01:08,152 SO IN CONCLUSION, HLA MATCHED 3083 02:01:08,152 --> 02:01:10,187 SIBLING AND HAPLOIDENTICAL 3084 02:01:10,187 --> 02:01:10,988 TRANSPLANT OFFER CURATIVE 3085 02:01:10,988 --> 02:01:12,189 OPTIONS FOR CHILDREN AND ADULTS 3086 02:01:12,189 --> 02:01:16,494 WITH SICKLE CELL. 3087 02:01:16,494 --> 02:01:18,195 WHILE PATIENTS WITH SICKLE CELL 3088 02:01:18,195 --> 02:01:20,097 HAVE A HIGHER RIX OF MYELOID 3089 02:01:20,097 --> 02:01:21,098 MALIGNANCIES THAN THE GENERAL 3090 02:01:21,098 --> 02:01:22,533 POPULATION, THE ABSOLUTE RISK IS 3091 02:01:22,533 --> 02:01:22,700 LOW. 3092 02:01:22,700 --> 02:01:24,668 THE THE INCIDENCE OF MYELOID 3093 02:01:24,668 --> 02:01:25,669 MALIGNANCIES IS HIGHER THAN 3094 02:01:25,669 --> 02:01:26,871 EXPECTED AFTER GRAFT FAILURE AND 3095 02:01:26,871 --> 02:01:27,805 GENE THERAPY FOR SICKLE CELL 3096 02:01:27,805 --> 02:01:28,539 DISEASE, AND THEREFORE THE GOAL 3097 02:01:28,539 --> 02:01:30,441 OF OUR FUEL TOUR PROTOCOLS HAS 3098 02:01:30,441 --> 02:01:32,309 SHIFTED FROM MIXED CHIMERISM TO 3099 02:01:32,309 --> 02:01:34,678 FULL DONOR CHIMERISM. 3100 02:01:34,678 --> 02:01:35,980 THERE'S NO RELIABLE BASELINE 3101 02:01:35,980 --> 02:01:37,181 SCREENING STUDIES CURRENTLY TO 3102 02:01:37,181 --> 02:01:39,884 ASSESS THE RISK OF LEUKEMIA 3103 02:01:39,884 --> 02:01:40,184 DEVELOPMENT. 3104 02:01:40,184 --> 02:01:41,519 I THINK I CAN JUST END THERE. 3105 02:01:41,519 --> 02:01:42,620 SO THANK YOU FOR YOUR ATTENTION. 3106 02:01:42,620 --> 02:01:49,260 [APPLAUSE] 3107 02:01:49,260 --> 02:01:50,828 >> THERE'S ONE QUESTION IN THE 3108 02:01:50,828 --> 02:01:51,295 CHAT. 3109 02:01:51,295 --> 02:01:53,664 THEY WANTED TO CLARIFY IF THESE 3110 02:01:53,664 --> 02:01:55,232 ARE IN THE NIH TRANSPLANT STUDY 3111 02:01:55,232 --> 02:01:58,102 AND NOT THE BBB STUDY. 3112 02:01:58,102 --> 02:02:00,571 >> SO TWO OF THE PATIENTS 3113 02:02:00,571 --> 02:02:02,640 DEVELOPED AML WHO WERE 3114 02:02:02,640 --> 02:02:04,408 TRANSPLANTED ON THE BLUEBIRD BIO 3115 02:02:04,408 --> 02:02:06,076 STUDY GROUP A AND THE REMAINING 3116 02:02:06,076 --> 02:02:07,745 WERE EITHER TRANSPLANTED HERE. 3117 02:02:07,745 --> 02:02:08,913 ONE WAS AT UNIVERSITY OF 3118 02:02:08,913 --> 02:02:13,484 ILLINOIS CHICAGO. 3119 02:02:13,484 --> 02:02:16,520 YES. 3120 02:02:16,520 --> 02:02:20,191 >> SO MANY YEARS AGO, WE 3121 02:02:20,191 --> 02:02:22,059 PUBLISHED THAT -- CELLS ARE 3122 02:02:22,059 --> 02:02:23,360 HIGHLY ACTIVATED IN SICKLE 3123 02:02:23,360 --> 02:02:24,662 CONDITION AND AT LEAST THREE 3124 02:02:24,662 --> 02:02:26,530 STUDIES FROM THREE DIFFERENT 3125 02:02:26,530 --> 02:02:27,698 COUNTRIES, VERY SMALL NUMBER OF 3126 02:02:27,698 --> 02:02:28,566 PATIENTS HAVE SHOWN THAT THEY 3127 02:02:28,566 --> 02:02:31,735 WERE TREATED WITH GLIVAC, WHICH 3128 02:02:31,735 --> 02:02:35,206 CAN INHIBIT THE -- AND THAT 3129 02:02:35,206 --> 02:02:37,074 RESOLVED THE SICKLE CELL CRISIS. 3130 02:02:37,074 --> 02:02:41,212 AND I'M JUST WONDERING IF THERE 3131 02:02:41,212 --> 02:02:42,880 IS MORE MYELOID DIFFERENTIATION 3132 02:02:42,880 --> 02:02:43,480 IN THESE PATIENTS. 3133 02:02:43,480 --> 02:02:45,049 LAST WEEK A VERY NICE PAPER IN 3134 02:02:45,049 --> 02:02:49,820 CELL WHICH PUBLISHED THAT A 3135 02:02:49,820 --> 02:02:51,689 HIGHER NEUTROPHIL ACTIVATION 3136 02:02:51,689 --> 02:02:53,724 ACTUALLY CAN BE SWALLOWED UP BY 3137 02:02:53,724 --> 02:02:55,926 THE MAST CELLS AND THERE IS THE 3138 02:02:55,926 --> 02:02:57,528 MUCH, MUCH HIGHER ACTIVATION. 3139 02:02:57,528 --> 02:03:00,497 AND I'M WONDERING IF MAST CELL 3140 02:03:00,497 --> 02:03:01,899 STABILIZERS CAN BE USED 3141 02:03:01,899 --> 02:03:03,467 ACCOMPANYING THE TRANSPLANT AND 3142 02:03:03,467 --> 02:03:05,936 OTHER THINGS AND THAT MIGHT HAVE 3143 02:03:05,936 --> 02:03:07,238 AN INHIBITORY EFFECT OR AT LEAST 3144 02:03:07,238 --> 02:03:08,639 BE CONSIDERED. 3145 02:03:08,639 --> 02:03:09,640 >> THAT'S SOMETHING THAT WE'LL 3146 02:03:09,640 --> 02:03:10,608 HAVE TO LOOK INTO MORE. 3147 02:03:10,608 --> 02:03:12,810 THANK YOU FOR THAT. 3148 02:03:12,810 --> 02:03:14,912 >> ALEXIS THOMPSON, CHILDREN'S 3149 02:03:14,912 --> 02:03:16,180 HOSPITAL OF PHILADELPHIA. 3150 02:03:16,180 --> 02:03:17,348 GREAT TALK, COURTNEY. 3151 02:03:17,348 --> 02:03:18,782 QUICK QUESTION FOR YOU, THOUGH. 3152 02:03:18,782 --> 02:03:20,184 IN YOUR CONCLUSION, YOU 3153 02:03:20,184 --> 02:03:22,720 MENTIONED THAT THERE IS NOT YET 3154 02:03:22,720 --> 02:03:25,322 CLARITY ON ANY PARTICULAR 3155 02:03:25,322 --> 02:03:26,824 GENETIC PREDISPOSITIONS THAT ONE 3156 02:03:26,824 --> 02:03:28,158 COULD SCREEN FOR. 3157 02:03:28,158 --> 02:03:30,227 QUESTION I GUESS FOR ME IS THAT 3158 02:03:30,227 --> 02:03:31,862 IT SEEMS LIKE ALMOST EVERY ONE 3159 02:03:31,862 --> 02:03:33,364 OF THE GENE THERAPY PROGRAMS HAS 3160 02:03:33,364 --> 02:03:35,532 ESTABLISHED SOME MITIGATION 3161 02:03:35,532 --> 02:03:38,335 STRATEGY AS REQUIRED BY THE FDA 3162 02:03:38,335 --> 02:03:40,070 IN RESPONSE TO THE MYELOID 3163 02:03:40,070 --> 02:03:40,671 MALIGNANCIES. 3164 02:03:40,671 --> 02:03:42,006 SO I GUESS I'M STRUGGLING A 3165 02:03:42,006 --> 02:03:43,774 LITTLE BIT BECAUSE I'M WORRIED 3166 02:03:43,774 --> 02:03:45,242 THAT WE ARE GOING DOWN A PATH 3167 02:03:45,242 --> 02:03:47,544 THAT IS NOT LIKELY TO ACTUALLY 3168 02:03:47,544 --> 02:03:49,313 GET US THE INFORMATION THAT 3169 02:03:49,313 --> 02:03:51,348 ACTUALLY WOULD BE ACTIONABLE. 3170 02:03:51,348 --> 02:03:53,884 AND SO IF I'M UNDERSTANDING YOU 3171 02:03:53,884 --> 02:03:54,885 RIGHT, IS THIS SOMETHING THAT WE 3172 02:03:54,885 --> 02:03:58,455 SHOULD CONTINUE TO PURSUE, THESE 3173 02:03:58,455 --> 02:03:59,556 PRETRANSPLANT PANELS? 3174 02:03:59,556 --> 02:04:01,825 >> I DO THINK IT'S IMPORTANT, I 3175 02:04:01,825 --> 02:04:02,927 GUESS CONCERNED ABOUT THAT TOO 3176 02:04:02,927 --> 02:04:04,028 BECAUSE THESE PANELS THAT ARE 3177 02:04:04,028 --> 02:04:06,497 BEING RUN DON'T LOOK AT REALLY 3178 02:04:06,497 --> 02:04:08,465 LOW LEVEL CLONAL HEMATOPOEISIS 3179 02:04:08,465 --> 02:04:12,703 AND I SHOWED YOU LEVELS AS LOW 3180 02:04:12,703 --> 02:04:14,338 AS 0.06% HAVE LED TO MDS IN ONE 3181 02:04:14,338 --> 02:04:14,905 OF OUR PATIENTS. 3182 02:04:14,905 --> 02:04:16,273 SO I THINK IT'S IMPORTANT TO 3183 02:04:16,273 --> 02:04:16,707 GATHER THE DATA. 3184 02:04:16,707 --> 02:04:18,275 I THINK IT'S IMPORTANT TO STORE 3185 02:04:18,275 --> 02:04:19,677 BLOOD IT ZO THAT ONCE WE 3186 02:04:19,677 --> 02:04:21,245 IDENTIFY RISK FACTORS, WE CAN 3187 02:04:21,245 --> 02:04:21,612 LOOK BACK. 3188 02:04:21,612 --> 02:04:22,913 THERE ARE LARGE STUDIES GOING ON 3189 02:04:22,913 --> 02:04:26,750 NOW TO LOOK AT PREVALENCE OF LOW 3190 02:04:26,750 --> 02:04:29,253 LEVEL CLONAL HEMATOPEE CYST, AND 3191 02:04:29,253 --> 02:04:34,391 WE'RE ALSO LOOKING AT CLONAL 3192 02:04:34,391 --> 02:04:35,392 HEMATOPOEISIS AFTER TRANSPLANT 3193 02:04:35,392 --> 02:04:37,861 IN OUR PATIENTS, SO STAY TUNED. 3194 02:04:37,861 --> 02:04:38,362 THANK YOU. 3195 02:04:38,362 --> 02:04:42,800 [APPLAUSE] 3196 02:04:42,800 --> 02:04:46,503 >> OUR NEXT SPEAKER IS VIRTUAL. 3197 02:04:46,503 --> 02:04:48,339 DAN IS GOING TO BE TALKING ABOUT 3198 02:04:48,339 --> 02:04:50,007 PRECISION GENE EDITING FOR 3199 02:04:50,007 --> 02:04:51,375 SICKLE CELL DISEASE. 3200 02:04:51,375 --> 02:04:58,816 TAKE IT AWAY. 3201 02:04:58,816 --> 02:05:00,351 YOU'RE MUTED, DAN. 3202 02:05:00,351 --> 02:05:00,551 OKAY. 3203 02:05:00,551 --> 02:05:02,753 >> GREAT. 3204 02:05:02,753 --> 02:05:04,054 >> WE CAN HEAR YOU NOW. 3205 02:05:04,054 --> 02:05:06,323 >> THANK YOU FOR THE OPPORTUNITY 3206 02:05:06,323 --> 02:05:07,424 TO PARTICIPATE IN THIS FANTASTIC 3207 02:05:07,424 --> 02:05:12,463 MEETING. 3208 02:05:12,463 --> 02:05:14,865 SO IT FEELS LIKE WE'RE FACING A 3209 02:05:14,865 --> 02:05:16,934 MOMENT OF COGNITIVE DISSIDENCE 3210 02:05:16,934 --> 02:05:18,535 WHERE ON THE ONE HAND, WE HAVE 3211 02:05:18,535 --> 02:05:21,105 THE REMARKABLE OPPORTUNITY TO 3212 02:05:21,105 --> 02:05:23,173 OFFER SICKLE CELL DISEASE 3213 02:05:23,173 --> 02:05:25,142 PATIENTS APPROVED GENETIC 3214 02:05:25,142 --> 02:05:25,909 MEDICINES, ON THE OTHER HAND, 3215 02:05:25,909 --> 02:05:32,016 THE THERAPIES ARE FLE -- COMPLE, 3216 02:05:32,016 --> 02:05:36,020 COSTLY, AND CANNOT -- OF AN 3217 02:05:36,020 --> 02:05:36,653 ESTIMATED 300,000 BABIES BORN 3218 02:05:36,653 --> 02:05:38,756 AROUND THE WORLD EACH YEAR WITH 3219 02:05:38,756 --> 02:05:39,189 SICKLE CELL DISEASE. 3220 02:05:39,189 --> 02:05:40,290 I WOULD ARGUE THIS MEANS WE 3221 02:05:40,290 --> 02:05:41,558 STILL NEED TO DEVELOP BETTER 3222 02:05:41,558 --> 02:05:42,993 APPROACHES THAT ARE SIMPLER, 3223 02:05:42,993 --> 02:05:48,098 SAFER, AND MORE EFFECTIVE. 3224 02:05:48,098 --> 02:05:54,438 HERE ARE MY DISCLOSURES. 3225 02:05:54,438 --> 02:05:56,740 CLINICAL OBSERVATIONS DATING 3226 02:05:56,740 --> 02:05:58,776 BACK TO THOSE OF JANET WATSON IN 3227 02:05:58,776 --> 02:06:00,310 THE 1940s INDICATE THAT 3228 02:06:00,310 --> 02:06:00,978 NEWBORNS WITH SICKLE CELL 3229 02:06:00,978 --> 02:06:02,179 DISEASE ARE PROTECTED DUE TO 3230 02:06:02,179 --> 02:06:04,448 HIGH LEVEL EXPRESSION OF FETAL 3231 02:06:04,448 --> 02:06:07,484 HEMOGLOBIN. 3232 02:06:07,484 --> 02:06:09,920 DISEASE ONLY BEGINS ONCE FETAL 3233 02:06:09,920 --> 02:06:12,423 GAMMA GLOBIN, THE PAIR LOG AND 3234 02:06:12,423 --> 02:06:14,491 GENOMIC NEIGHBOR OF ADULT BETA 3235 02:06:14,491 --> 02:06:15,592 GLOBIN HAS BEEN 3236 02:06:15,592 --> 02:06:16,927 TRANSCRIPTIONALLY SILENCED AFTER 3237 02:06:16,927 --> 02:06:17,561 BIRTH. 3238 02:06:17,561 --> 02:06:18,762 THE LONG-STANDING GOAL OF 3239 02:06:18,762 --> 02:06:20,297 HEMATOLOGY HAS BEEN TO DEEPLY 3240 02:06:20,297 --> 02:06:21,832 UNDERSTAND HEMOGLOBIN SWITCHING 3241 02:06:21,832 --> 02:06:25,002 TO ENABLE THERAPEUTIC INDUCTION 3242 02:06:25,002 --> 02:06:26,970 OF FETAL HEMOGLOBIN. 3243 02:06:26,970 --> 02:06:32,009 WHEN I JOINED STU ORKIN'S LAB AS 3244 02:06:32,009 --> 02:06:35,145 A FELLOW, I BECAME INTERESTED OF 3245 02:06:35,145 --> 02:06:38,115 HOW COMMON GENETIC VARIATION AT 3246 02:06:38,115 --> 02:06:39,883 BCL11A INFLUENCED FETAL 3247 02:06:39,883 --> 02:06:40,184 HEMOGLOBIN. 3248 02:06:40,184 --> 02:06:49,460 WE OBSERVED DISEASE ASSOCIA 3249 02:06:49,460 --> 02:06:50,561 ASSOCIATED -- BECAUSE GENE 3250 02:06:50,561 --> 02:06:52,963 EDITING CAN DISRUPT THE 3251 02:06:52,963 --> 02:06:54,398 SEQUENCES IN MOUTHY RIT ROID 3252 02:06:54,398 --> 02:06:57,101 CELL LINE AND OBSERVED THAT 3253 02:06:57,101 --> 02:06:59,603 ERYTHROID BCL11A ERYTHROID 3254 02:06:59,603 --> 02:07:04,108 ENHANCERS WERE ESSENTIALLY -- 3255 02:07:04,108 --> 02:07:11,181 FOR BCL11A EXPRESSION. 3256 02:07:11,181 --> 02:07:14,885 NEXT, CRISPR DENSE MU TOE 3257 02:07:14,885 --> 02:07:16,653 GENESIS -- THAT COULD SERVE AS 3258 02:07:16,653 --> 02:07:18,722 THERAPEUTIC TARGETS. 3259 02:07:18,722 --> 02:07:22,893 WE FOUND GATA1 BINDING SITES AT 3260 02:07:22,893 --> 02:07:26,463 THE PLUS 50A -- THAT WERE 3261 02:07:26,463 --> 02:07:28,365 REQUIRED FOR ROBUST FETAL 3262 02:07:28,365 --> 02:07:28,999 HEMOGLOBIN SILENCING. 3263 02:07:28,999 --> 02:07:30,634 THIS LED TO A SIMPLE THERAPEUTIC 3264 02:07:30,634 --> 02:07:33,370 VISION TO DISRUPT THE BCL11A 3265 02:07:33,370 --> 02:07:35,305 ENHANCER IN HEMATOPOIETIC STEM 3266 02:07:35,305 --> 02:07:38,375 CELLS, LEADING TO REDUCTION OF 3267 02:07:38,375 --> 02:07:40,744 BCL11A SPECIFICALLY IN ERYTHROID 3268 02:07:40,744 --> 02:07:42,379 PRECURSORS, AND SUBSEQUENT D 3269 02:07:42,379 --> 02:07:45,649 REPRESSION OF FETAL HEMOGLOBIN. 3270 02:07:45,649 --> 02:07:47,718 EX-VO VO MODIFIED LP STEM CELLS 3271 02:07:47,718 --> 02:07:49,686 COULD SERVE AS AN AUTOLOGOUS 3272 02:07:49,686 --> 02:07:50,888 GRAFT FOR HEMATOPOIETIC 3273 02:07:50,888 --> 02:07:53,857 TRANSPLANT. 3274 02:07:53,857 --> 02:07:54,925 RECENT CLINICAL TRIALS SPONSORED 3275 02:07:54,925 --> 02:07:56,860 BY CRISPR THERAPEUTICS AND 3276 02:07:56,860 --> 02:07:58,929 VERTEX HAVE SHOWN THAT IN 43 3277 02:07:58,929 --> 02:08:01,131 SICKLE CELL DISEASE PATIENTS, EX 3278 02:08:01,131 --> 02:08:04,168 VIVO GENE EDITING CAN PRODUCE 3279 02:08:04,168 --> 02:08:06,904 EFFICIENT INDELLS IN BLOOD 3280 02:08:06,904 --> 02:08:08,005 CELLS. 3281 02:08:08,005 --> 02:08:09,206 POTENT FETAL HEMOGLOBIN 3282 02:08:09,206 --> 02:08:10,841 INDUCTION COMPRISING ABOUT 40% 3283 02:08:10,841 --> 02:08:14,678 OF TOTAL HEMOGLOBIN, IMPROVEMENT 3284 02:08:14,678 --> 02:08:18,248 IN HEMOLYSIS AND REDUCTION IN 3285 02:08:18,248 --> 02:08:18,882 VASO-OCCLUSIVE CRISIS FREQUENCY 3286 02:08:18,882 --> 02:08:22,819 LEADING TO THE FDA AKROFL IN 3287 02:08:22,819 --> 02:08:26,223 DECEMBER OF 2023 OF CASGEVY. 3288 02:08:26,223 --> 02:08:31,495 NONNONT LESS, PATIENTS HAD SOME 3289 02:08:31,495 --> 02:08:35,465 RESIDUAL HEMOLYSIS AND -- THE 3290 02:08:35,465 --> 02:08:37,501 IMPACT ON THE INSIDIOUS 3291 02:08:37,501 --> 02:08:38,635 DETERIORATION CHARACTERISTIC OF 3292 02:08:38,635 --> 02:08:40,170 SICKLE CELL DISEASE ORGAN 3293 02:08:40,170 --> 02:08:42,139 FUNCTION IN LONG TERM OUTCOMES 3294 02:08:42,139 --> 02:08:48,445 REMAIN UNKNOWN. 3295 02:08:48,445 --> 02:08:50,280 THIS STUDY REPORTS A BRAZILIAN 3296 02:08:50,280 --> 02:08:55,219 COHORT OF HEMOGLOBIN S HPFH 3297 02:08:55,219 --> 02:08:57,287 COMPOUND HETEROSIGH JUST 3298 02:08:57,287 --> 02:09:00,023 CHILDREN WITH MEAN HEMOGLOBIN -- 3299 02:09:00,023 --> 02:09:02,392 AND FETAL ABOUT 42%, SIMILAR 3300 02:09:02,392 --> 02:09:04,461 VALUES AS REPORTED IN THE RECENT 3301 02:09:04,461 --> 02:09:07,297 CLINICAL TRIAL REVEALED GREAT 3302 02:09:07,297 --> 02:09:08,065 AMELIORATION OF SICKLE CELL 3303 02:09:08,065 --> 02:09:10,267 DISEASE, BUT STILL SOME EPISODES 3304 02:09:10,267 --> 02:09:11,668 OF ACUTE CHEST SYNDROME, ACUTE 3305 02:09:11,668 --> 02:09:14,037 PAIN CRISES AND TRANSFUSION 3306 02:09:14,037 --> 02:09:15,606 REQUIREMENTS SUGGESTING CLINICAL 3307 02:09:15,606 --> 02:09:16,740 MANIFESTATIONS OF SICKLE CELL 3308 02:09:16,740 --> 02:09:18,442 DISEASE WERE NOT COMPLETELY 3309 02:09:18,442 --> 02:09:21,178 REVERSED. 3310 02:09:21,178 --> 02:09:23,614 WE KNOW THAT INDIVIDUALS WITH 3311 02:09:23,614 --> 02:09:25,148 SICKLE CELL TRAIT WITH A 3312 02:09:25,148 --> 02:09:26,984 HETEROZYGOUS HBS MUTATION ARE 3313 02:09:26,984 --> 02:09:28,085 LARGELY HEALTHY. 3314 02:09:28,085 --> 02:09:30,254 UNDER VENOUS OXYGEN TENSION OF 3315 02:09:30,254 --> 02:09:33,190 ABOUT 4%, IT TAKES ABOUT 65% 3316 02:09:33,190 --> 02:09:35,292 ADULT HEMOGLOBIN TO PREVENT 3317 02:09:35,292 --> 02:09:36,360 SICKLING, WHICH IS THE PRECISE 3318 02:09:36,360 --> 02:09:38,395 DX OF ADULT HEMOGLOBIN FOUND IN 3319 02:09:38,395 --> 02:09:40,297 SICKLE CELL TRAIT. 3320 02:09:40,297 --> 02:09:42,266 50% FETAL HEMOGLOBIN WOULD BE 3321 02:09:42,266 --> 02:09:43,800 EXPECTED TO ACHIEVE A 3322 02:09:43,800 --> 02:09:45,202 SIMILAR DEGREE OF SICKLING 3323 02:09:45,202 --> 02:09:45,902 PROTECTION. 3324 02:09:45,902 --> 02:09:48,038 SUGGESTING THAT SLIGHTLY MORE 3325 02:09:48,038 --> 02:09:49,473 ROBUST FETAL HEMOGLOBIN 3326 02:09:49,473 --> 02:09:51,241 INDUCTION MIGHT YIELD CLINICAL 3327 02:09:51,241 --> 02:09:52,909 OUTCOMES NON-INFERIOR TO SICKLE 3328 02:09:52,909 --> 02:09:56,246 CELL TRAIT. 3329 02:09:56,246 --> 02:09:59,883 RECENT WORK FROM MY LAB LED BY 3330 02:09:59,883 --> 02:10:02,552 JIN DP. ZENG SHOWS THE COMBINED 3331 02:10:02,552 --> 02:10:05,222 TARGETING OF THE TWO MAJOR 3332 02:10:05,222 --> 02:10:08,158 BCLA11 ENHANCERS PRODUCES 3333 02:10:08,158 --> 02:10:14,598 SUPERIOR ENHANCER DISRUPTION. 3334 02:10:14,598 --> 02:10:16,566 COMPARED TO SINGLE ENHANCER 3335 02:10:16,566 --> 02:10:18,735 DISRUPTION OR ALTERNATIVE 3336 02:10:18,735 --> 02:10:21,505 APPROACHES LIKE BCL11A KNOCKDOWN 3337 02:10:21,505 --> 02:10:25,842 OR TARGET THE PROMOTER 115 SITE 3338 02:10:25,842 --> 02:10:28,445 COMBINED BCR11A ENHANCER EDITING 3339 02:10:28,445 --> 02:10:29,980 PRODUCED THE GREATEST FETAL 3340 02:10:29,980 --> 02:10:31,181 HEMOGLOBIN INDUCTION AND 3341 02:10:31,181 --> 02:10:34,051 PREVENTION OF IN VITRO OR 3342 02:10:34,051 --> 02:10:37,821 ERYTHROCYTE SICKLING. 3343 02:10:37,821 --> 02:10:40,257 ATTRIBUTABLE TO -- UP TO FOUR 3344 02:10:40,257 --> 02:10:41,925 TOTAL BINDING SITES DISRUPTED 3345 02:10:41,925 --> 02:10:46,563 PER CELL. 3346 02:10:46,563 --> 02:10:50,300 WITH OUR COLLEAGUES AT NHLBI, WE 3347 02:10:50,300 --> 02:10:52,602 TESTED THIS COMBINED ENHANCER 3348 02:10:52,602 --> 02:10:56,606 GENE EDITING PROTOCOL IN THE 3349 02:10:56,606 --> 02:10:59,142 RHESUS MACAQUE GENE EDITING -- 3350 02:10:59,142 --> 02:11:00,210 INCLUDING MOBILIZING, 3351 02:11:00,210 --> 02:11:02,112 COLLECTING, PURIFYING 3352 02:11:02,112 --> 02:11:02,846 HEMATOPOIETIC STEM CELLS PRIOR 3353 02:11:02,846 --> 02:11:05,816 TO GENE EDITING EX VIVO AND YOU 3354 02:11:05,816 --> 02:11:06,883 AUTOLOGOUS INFUSION. 3355 02:11:06,883 --> 02:11:08,752 WE TESTED TWO COHORTS, ONE 3356 02:11:08,752 --> 02:11:11,121 TREATED WITH STANDARD BUSULFAN 3357 02:11:11,121 --> 02:11:12,022 CHEMOTHERAPY, AND THE OTHER 3358 02:11:12,022 --> 02:11:16,259 TREATED WITH AN ANTICD45 3359 02:11:16,259 --> 02:11:24,701 ANTIBODY DRUG CONGUGATE. 3360 02:11:24,701 --> 02:11:27,170 >> WITH OR WITHOUT CHEMOTHERAPY 3361 02:11:27,170 --> 02:11:28,739 OVER AT LEAST A YEAR FOLLOW-UP, 3362 02:11:28,739 --> 02:11:30,340 PROVIDING PROOF OF CONCEPT THAT 3363 02:11:30,340 --> 02:11:32,542 CHEMOTHERAPY IS NOT REQUIRED FOR 3364 02:11:32,542 --> 02:11:34,177 EFFECTIVE HEMATOPOIETIC 3365 02:11:34,177 --> 02:11:35,479 RECONSTITUTION BY GENE EDITED 3366 02:11:35,479 --> 02:11:40,550 CELLS. 3367 02:11:40,550 --> 02:11:42,519 ONE POSSIBLE RISK OF GENE ID 3368 02:11:42,519 --> 02:11:44,488 ITING IS OFF TARGET EFFECTS. 3369 02:11:44,488 --> 02:11:46,123 WITH OUR BIOINFORMATIC 3370 02:11:46,123 --> 02:11:48,291 COLLEAGUES, WE BUILT A TOOL 3371 02:11:48,291 --> 02:11:58,235 CALLED CRISPRME. 3372 02:11:58,235 --> 02:11:59,669 THE GENETIC VARIANT SHOWN ON THE 3373 02:11:59,669 --> 02:12:03,640 LEFT IN BLUE WHICH CREATES A PAN 3374 02:12:03,640 --> 02:12:06,309 SEQUENCE WHICH ALLOWS TO BIND AT 3375 02:12:06,309 --> 02:12:08,378 THE ADJACENT SITE WITH JUST 3376 02:12:08,378 --> 02:12:09,613 THREE MISMATCHES. 3377 02:12:09,613 --> 02:12:12,682 THIS VARIANT IS FOUND IN ABOUT 3378 02:12:12,682 --> 02:12:14,518 5% ALLELE FREQUENCY IN AFRICAN 3379 02:12:14,518 --> 02:12:15,352 ANCESTRY INDIVIDUALS, SUGGESTING 3380 02:12:15,352 --> 02:12:18,455 THAT UP TO 1 IN 10 SICKLE CELL 3381 02:12:18,455 --> 02:12:19,423 DISEASE PATIENTS MIGHT CARRY 3382 02:12:19,423 --> 02:12:19,956 THIS VARIANT. 3383 02:12:19,956 --> 02:12:21,725 SINCE THE OFF-TARGET SITE IS ON 3384 02:12:21,725 --> 02:12:24,561 THE Q ARM OF CHROMOSOME 2, MORE 3385 02:12:24,561 --> 02:12:27,831 THAN 150 MEGA BASES FROM THE 3386 02:12:27,831 --> 02:12:30,133 BCL11A TARGET SITE ON THE P ARM, 3387 02:12:30,133 --> 02:12:31,635 WE HYPOTHESIZE THAT SIMULTANEOUS 3388 02:12:31,635 --> 02:12:32,636 CLEAVAGE OF THE SITES COULD 3389 02:12:32,636 --> 02:12:34,404 RESULT IN PERICENTRIC INVERSIONS 3390 02:12:34,404 --> 02:12:36,873 WHICH INDEED WE CONFIRMED WERE 3391 02:12:36,873 --> 02:12:39,376 PRESENT AT ABOUT 1 IN 600 ALLELE 3392 02:12:39,376 --> 02:12:41,578 FREQUENCY AFTER GENE EDITING IN 3393 02:12:41,578 --> 02:12:42,512 DONOR HEMATOPOIETIC CELLS 3394 02:12:42,512 --> 02:12:44,514 CARRYING A HETEROZYGOUS RISK 3395 02:12:44,514 --> 02:12:45,515 VARIANT. 3396 02:12:45,515 --> 02:12:47,150 WE THINK GENETIC VARIANT 3397 02:12:47,150 --> 02:12:49,820 ASSOCIATED OFF-TARGET EDITING IS 3398 02:12:49,820 --> 02:12:51,388 A GENERIC RISK OF GENE EDITING 3399 02:12:51,388 --> 02:12:52,923 AND SHOULD BE CONSIDERED IN 3400 02:12:52,923 --> 02:12:54,224 EDITING DESIGN, PATIENT 3401 02:12:54,224 --> 02:12:55,525 SCREENING AND CLINICAL 3402 02:12:55,525 --> 02:12:59,029 FOLLOW-UP. 3403 02:12:59,029 --> 02:13:02,399 ALONGSIDE ITS APPROVAL OF 3404 02:13:02,399 --> 02:13:03,834 CASGEVY IN DECEMBER 2023, THE 3405 02:13:03,834 --> 02:13:05,602 FDA MANDATED A POST MARKETING 3406 02:13:05,602 --> 02:13:06,803 SURVEILLANCE STUDY TO SCREEN 3407 02:13:06,803 --> 02:13:09,072 PATIENTS FOR THE CPS1 VARIANT 3408 02:13:09,072 --> 02:13:11,508 AND ASSESS FOR GENETIC 3409 02:13:11,508 --> 02:13:12,342 VARIANT-ASSOCIATED OFF TARGET 3410 02:13:12,342 --> 02:13:16,046 EDITING. 3411 02:13:16,046 --> 02:13:17,347 MANY POTENTIAL GENETIC VARIANT 3412 02:13:17,347 --> 02:13:18,682 ASSOCIATED OFF-TARGET EFFECTS 3413 02:13:18,682 --> 02:13:21,318 ARE DUE TO MUCH RARER VARIANTS 3414 02:13:21,318 --> 02:13:23,353 THAN THE CPS1 VARIANT WHICH 3415 02:13:23,353 --> 02:13:26,223 MIGHT MAKE IT INFEASIBLE TO FIND 3416 02:13:26,223 --> 02:13:28,158 DONORS FOR EXPERIMENTAL TESTING. 3417 02:13:28,158 --> 02:13:29,493 HERE I'M SHOWING THE MINOR 3418 02:13:29,493 --> 02:13:32,562 ALLELE FREQUENCY OF 72 CANDIDATE 3419 02:13:32,562 --> 02:13:34,631 VARIANT ASSOCIATED OFF TARGETS 3420 02:13:34,631 --> 02:13:37,033 WITH A SCORE OF AT LEAST 0.4. 3421 02:13:37,033 --> 02:13:38,134 MOST ASSOCIATED WITH VERY RARE 3422 02:13:38,134 --> 02:13:39,336 GENETIC VARIANTS. 3423 02:13:39,336 --> 02:13:41,838 IT WOULD NOT BE FEASIBLE TO 3424 02:13:41,838 --> 02:13:43,607 OBTAIN CD34 CELLS IN DONORS 3425 02:13:43,607 --> 02:13:44,941 CARRYING EACH OF THESE VARIANTS 3426 02:13:44,941 --> 02:13:46,343 FOR DIRECT OFF-TARGET 3427 02:13:46,343 --> 02:13:47,944 ASSESSMENT. 3428 02:13:47,944 --> 02:13:49,579 TO ADDRESS THIS CHALLENGE, WE'VE 3429 02:13:49,579 --> 02:13:50,881 DEVELOPED AN ASSAY THAT CAN 3430 02:13:50,881 --> 02:13:54,417 ASSESS THESE 3431 02:13:54,417 --> 02:13:55,485 EDITED FOR MAINTAINING 3432 02:13:55,485 --> 02:13:57,020 CLINICALLY RELEVANT CELLULAR AND 3433 02:13:57,020 --> 02:14:01,591 GENE EDITING DELIVERY CONTEXT. 3434 02:14:01,591 --> 02:14:05,028 THE EXPERIMENTAL DESIGN OF OUR 3435 02:14:05,028 --> 02:14:11,034 SO-CALLED ABSOLVE SEQ ASSAY 3436 02:14:11,034 --> 02:14:12,736 INTRODUCED ALTERNATIVE ALLELE 3437 02:14:12,736 --> 02:14:16,573 SEQUENCES TO CD34 CELLS AND 3438 02:14:16,573 --> 02:14:18,308 PERFORMING EDITING WITH 3439 02:14:18,308 --> 02:14:19,910 CLINICALLY RELEVANT PROTOCOLS 3440 02:14:19,910 --> 02:14:22,245 AND MOLECULAR IDENTIFIERS TO 3441 02:14:22,245 --> 02:14:26,082 DETECT SINGLE EDITING EVENTS AND 3442 02:14:26,082 --> 02:14:27,784 PULLED THEM TOGETHER AND 3443 02:14:27,784 --> 02:14:30,220 INCLUDED BAR CODES TO 3444 02:14:30,220 --> 02:14:31,421 DIFFERENTIATE TARGETS AND 3445 02:14:31,421 --> 02:14:35,959 DEVELOPED A COMPUTATIONAL 3446 02:14:35,959 --> 02:14:38,562 PIPELINE IN TO ASSESS THE 3447 02:14:38,562 --> 02:14:39,963 TARGETING SITE. 3448 02:14:39,963 --> 02:14:42,198 HERE'S THE RESULTS WITH 72 PROXY 3449 02:14:42,198 --> 02:14:48,805 OFF TARGETS TO CD34 CELLS 3450 02:14:48,805 --> 02:14:54,477 FOLLOWED BY THE KAS 9 AND GUIDE 3451 02:14:54,477 --> 02:14:57,380 RNAs AND THE TWO ON TARGET PROXY 3452 02:14:57,380 --> 02:14:59,149 SEQUENCES AND THE ONE KNOWN 3453 02:14:59,149 --> 02:15:02,319 VARIANT OFF TARGET AT CPS1 3454 02:15:02,319 --> 02:15:03,954 SHOWING SIGNIFICANT INCREASE IN 3455 02:15:03,954 --> 02:15:05,789 THE TREATED SAMPLE. 3456 02:15:05,789 --> 02:15:08,925 OF THE 72 VARIANT ASSOCIATED 3457 02:15:08,925 --> 02:15:10,393 CANDIDATE OFF TARGETS NONE 3458 02:15:10,393 --> 02:15:12,462 SHOWED SIGNIFICANT PROXY 3459 02:15:12,462 --> 02:15:12,696 EDITING. 3460 02:15:12,696 --> 02:15:14,097 THOUGH THIS WAS REASSURING FOR 3461 02:15:14,097 --> 02:15:18,034 OUR EDITING APPROACH WE HOPE 3462 02:15:18,034 --> 02:15:21,037 MORE BROADLY IT SHOWS A STRATEGY 3463 02:15:21,037 --> 02:15:22,539 FOR NOVEL CANDIDATE GENE 3464 02:15:22,539 --> 02:15:26,376 EDITORS. 3465 02:15:26,376 --> 02:15:27,944 WE HAVE GREAT OPPORTUNITIES 3466 02:15:27,944 --> 02:15:28,812 AHEAD FOR SICKLE CELL DISEASE 3467 02:15:28,812 --> 02:15:30,480 THERAPY TO GENE EDITING. 3468 02:15:30,480 --> 02:15:33,483 WITH GENETIC MEDICINE WE CAN 3469 02:15:33,483 --> 02:15:35,518 AASPIRE TO PUBLIC A LARGE IMPACT 3470 02:15:35,518 --> 02:15:37,687 ON THE CLINICAL UNMET NEED. 3471 02:15:37,687 --> 02:15:39,222 DUE TO THE ACCESSIBILITY OF THE 3472 02:15:39,222 --> 02:15:40,957 BLOOD SYSTEM WE CAN EXPECT TO 3473 02:15:40,957 --> 02:15:43,093 DEEPLY UNDERSTAND THE IMPACT OF 3474 02:15:43,093 --> 02:15:45,195 GENE EDITING AT MOLECULAR, 3475 02:15:45,195 --> 02:15:47,530 CELLULAR AND PHYSIOLOGIC LEVELS 3476 02:15:47,530 --> 02:15:52,068 WITH INDEFINITE FOLLOW-UP. 3477 02:15:52,068 --> 02:15:54,337 I'M EXTREMELY GRATEFUL TO 3478 02:15:54,337 --> 02:15:58,541 CURRENT AND FORMER LAB MEMBERS 3479 02:15:58,541 --> 02:16:00,710 AND MENTORS, COLLABORATORS AND 3480 02:16:00,710 --> 02:16:03,947 SICKLE CELL DISEASE PATIENTS. 3481 02:16:03,947 --> 02:16:14,124 THANK YOU. 3482 02:16:14,524 --> 02:16:17,894 >> QUESTIONS ONLINE OR HERE IN 3483 02:16:17,894 --> 02:16:19,929 THE AUDIENCE? 3484 02:16:19,929 --> 02:16:24,768 THERE'S ONE. 3485 02:16:24,768 --> 02:16:31,041 >> VERY ELEGANT WORK BUT I'M 3486 02:16:31,041 --> 02:16:33,610 INTRIGUED BY ONE OBSERVATION 3487 02:16:33,610 --> 02:16:35,979 WHICH HAS COME TO LIGHT MORE 3488 02:16:35,979 --> 02:16:39,916 RECENTLY THAT IN INDIA MOST THE 3489 02:16:39,916 --> 02:16:42,085 SICKLE CELL PATIENTS HAVE VERY 3490 02:16:42,085 --> 02:16:44,854 HIGH HEMOGLOBIN F WHICH PERSISTS 3491 02:16:44,854 --> 02:16:48,258 THROUGHOUT THEIR LIFE UP TO IN 3492 02:16:48,258 --> 02:16:51,861 30% OR SO. 3493 02:16:51,861 --> 02:16:55,732 SO, THEY HAVE COMORBIDITIES 3494 02:16:55,732 --> 02:16:57,867 SIMILAR TO THOSE WHO HAVE LOWER 3495 02:16:57,867 --> 02:16:59,936 HPF IN OTHER PARTS OF THE WORLD. 3496 02:16:59,936 --> 02:17:04,074 SO HOW WOULD THIS WORK IN THOSE 3497 02:17:04,074 --> 02:17:07,110 AND HOW DO WE REALLY EXPLAIN 3498 02:17:07,110 --> 02:17:07,377 THAT? 3499 02:17:07,377 --> 02:17:09,579 >> YEAH. 3500 02:17:09,579 --> 02:17:11,147 IT'S A GREAT QUESTION. 3501 02:17:11,147 --> 02:17:14,751 I THINK IT HIGHLIGHTS THE NEED 3502 02:17:14,751 --> 02:17:18,354 FOR LONG-TERM FOLLOW-UP IN 3503 02:17:18,354 --> 02:17:20,156 SICKLE CELL DISEASE BOTH TO 3504 02:17:20,156 --> 02:17:24,127 REALLY UNDERSTAND THE NATURAL 3505 02:17:24,127 --> 02:17:27,964 HISTORY OF HETEROGENEOUS DISEASE 3506 02:17:27,964 --> 02:17:31,267 AND THE RESPONSE OF NOVEL 3507 02:17:31,267 --> 02:17:32,469 THERAPIES AND WE'RE SORT OF 3508 02:17:32,469 --> 02:17:34,137 BLESSED TO HAVE MANY THERAPIES 3509 02:17:34,137 --> 02:17:36,139 COMING ON BOARD BUT REQUIRES AN 3510 02:17:36,139 --> 02:17:38,875 ONUS ON US TO FOLLOW PATIENTS 3511 02:17:38,875 --> 02:17:42,145 AND UNDERSTAND THE OUTCOME. 3512 02:17:42,145 --> 02:17:46,015 FETAL HEMOGLOBIN LEVEL DEPENDS 3513 02:17:46,015 --> 02:17:47,784 ON THE ABSOLUTE LEVEL WITHIN THE 3514 02:17:47,784 --> 02:17:49,953 RED CELL AND DISTRIBUTION OF THE 3515 02:17:49,953 --> 02:17:51,488 RED CELLS AND POPULATION OF THE 3516 02:17:51,488 --> 02:17:54,257 RED CELLS AND THE SURVIVAL OF 3517 02:17:54,257 --> 02:17:55,625 THOSE RED CELLS AS DR. LEONARD 3518 02:17:55,625 --> 02:17:58,795 INTRODUCED EARLIER TODAY. 3519 02:17:58,795 --> 02:18:03,500 AND SO I THINK WE HAVE AN 3520 02:18:03,500 --> 02:18:05,869 UNDERSTANDING OF HOW THE 3521 02:18:05,869 --> 02:18:07,937 DISTRIBUTIONS ARE PRESENT IN 3522 02:18:07,937 --> 02:18:10,573 VARIOUS PATIENTS AND HOW THEY'RE 3523 02:18:10,573 --> 02:18:12,776 ASSOCIATED WITH CLINICAL OUTCOME 3524 02:18:12,776 --> 02:18:16,312 BUT MAY NEED HIGHER LEVELS OF 3525 02:18:16,312 --> 02:18:19,516 FETAL HEMOGLOBIN TO REALLY HAVE 3526 02:18:19,516 --> 02:18:20,984 THE BEST POSSIBLE OUTCOMES WHICH 3527 02:18:20,984 --> 02:18:24,020 I WOULD SAY ARE NON INFERIOR TO 3528 02:18:24,020 --> 02:18:34,531 THOSE WITH SICKLE CELL TRAIT. 3529 02:18:36,132 --> 02:18:36,966 >> THANK YOU FOR A WONDERFUL 3530 02:18:36,966 --> 02:18:37,233 TALK. 3531 02:18:37,233 --> 02:18:44,407 WE HAVE OUR NEXT TALK IS GENE 3532 02:18:44,407 --> 02:18:48,111 CORRECTION OF THE NUCLEOTIDE 3533 02:18:48,111 --> 02:18:48,912 VARIANT OF SICKLE CELL DISEASE 3534 02:18:48,912 --> 02:18:50,980 PROGRESS AND UPDATES. 3535 02:18:50,980 --> 02:18:51,781 MATTHEW PORTEUS. 3536 02:18:51,781 --> 02:18:53,616 >> THANK YOU FOR INVITING ME AND 3537 02:18:53,616 --> 02:18:55,285 THANK YOU FOR BEING HERE. 3538 02:18:55,285 --> 02:18:58,822 I'M GOING TO GIVE AN UPDATE ON A 3539 02:18:58,822 --> 02:18:59,422 SINGLE PATIENT CLINICAL TRIAL 3540 02:18:59,422 --> 02:19:09,699 AND WHERE WE'RE GOING. 3541 02:19:09,699 --> 02:19:12,268 THESE ARE MY DISCLOSURES FOR 3542 02:19:12,268 --> 02:19:14,771 THERAPEUTICS WHO HAVE TAKEN OVER 3543 02:19:14,771 --> 02:19:15,572 SPONSORSHIP OF A CLINICAL TRIAL 3544 02:19:15,572 --> 02:19:19,509 I'M GOING TO DESCRIBE. 3545 02:19:19,509 --> 02:19:21,644 WE'RE INTERESTED IN HARNESSING 3546 02:19:21,644 --> 02:19:26,349 THE PATHWAY OF GENE EDITING IN 3547 02:19:26,349 --> 02:19:28,651 WHICH A CRISPR IS USED TO MAKE A 3548 02:19:28,651 --> 02:19:31,187 BREAK BUT INSTEAD OF ALLOWING IT 3549 02:19:31,187 --> 02:19:33,156 TO BE REPAIRED WE PROVIDED A 3550 02:19:33,156 --> 02:19:35,258 DONOR THAT ALLOWS THE REPAIR TO 3551 02:19:35,258 --> 02:19:38,294 BE TEMPLATED BY THE DONOR AND 3552 02:19:38,294 --> 02:19:41,397 INTRODUCED PRECISELY FOR THE 3553 02:19:41,397 --> 02:19:41,965 CHANGES. 3554 02:19:41,965 --> 02:19:44,300 THE FLEXIBILITY OF 3555 02:19:44,300 --> 02:19:47,837 MULTI-DIRECTIVE REPAIR IS 3556 02:19:47,837 --> 02:19:48,338 FANTASTIC. 3557 02:19:48,338 --> 02:19:57,614 YOU CAN PUT IN LARGE SETS AND 3558 02:19:57,614 --> 02:20:01,184 REVERSING TO A NON-PATH LOGIC 3559 02:20:01,184 --> 02:20:05,054 AND THIS IS HIGHLY RELEVANT TO 3560 02:20:05,054 --> 02:20:07,957 SICKLE CELL DISEASE WHERE EVERY 3561 02:20:07,957 --> 02:20:13,663 PATIENT CARRIES AND THE GAG 3562 02:20:13,663 --> 02:20:16,666 MAKING TO A POLAR INSTEAD OF A 3563 02:20:16,666 --> 02:20:22,338 CHARGE ACID. 3564 02:20:22,338 --> 02:20:26,109 SO 2016 WE PUBLISHED A CONCEPT 3565 02:20:26,109 --> 02:20:29,178 PAPER IN NATURE SHOWING WE CAN 3566 02:20:29,178 --> 02:20:34,017 HARNESS THE PROTEIN DELIVERY OF 3567 02:20:34,017 --> 02:20:37,754 THE CRISPR KAS 9 FOR TEMPLATE TO 3568 02:20:37,754 --> 02:20:37,987 REPAIR. 3569 02:20:37,987 --> 02:20:41,224 WHAT I WANT TO HIGHLIGHT IS THE 3570 02:20:41,224 --> 02:20:45,428 REVERSE TO THE NON-PATHOLOGIC A 3571 02:20:45,428 --> 02:20:52,535 AND SILENCE MUE TAILITIONS AND A 3572 02:20:52,535 --> 02:20:55,038 PAPER IN SCIENCE AND MEDICINE IN 3573 02:20:55,038 --> 02:21:01,177 2021 WE PUBLISHED ON OUR SCALE 3574 02:21:01,177 --> 02:21:02,145 UP AND STUDIES. 3575 02:21:02,145 --> 02:21:08,518 IN THIS WORK WE ACTUALLY SHOWED 3576 02:21:08,518 --> 02:21:10,453 IN VITRO WHEN RED BLOOD CELLS 3577 02:21:10,453 --> 02:21:13,423 WERE DIFFERENTIATED FROM CD34 3578 02:21:13,423 --> 02:21:15,925 CELLS FROM PATIENTS WITH SICKLE 3579 02:21:15,925 --> 02:21:19,595 CELL DISEASE AND UNMODIFIED 3580 02:21:19,595 --> 02:21:22,398 CELLS GENERATED HIGH AMOUNTS OF 3581 02:21:22,398 --> 02:21:25,201 HEMOGLOBIN S AND WE GOT HIGH 3582 02:21:25,201 --> 02:21:30,540 LEVELS OF HEMOGLOBIN A AND FETAL 3583 02:21:30,540 --> 02:21:33,810 HEMOGLOBIN I ATTRIBUTED TO THE 3584 02:21:33,810 --> 02:21:35,945 ARTIFACT OF DIFFERENT SYSTEMS 3585 02:21:35,945 --> 02:21:38,247 AND IT MAY BE RELATED TO OUR 3586 02:21:38,247 --> 02:21:39,682 FIRST PATIENT. 3587 02:21:39,682 --> 02:21:45,855 SO WE TRANSFERRED THE PROTOCOL 3588 02:21:45,855 --> 02:21:52,328 TO GRAPHITE BIO WHO TREATED A 3589 02:21:52,328 --> 02:21:53,429 PATIENT WITH THE PROTOCOL ALMOST 3590 02:21:53,429 --> 02:21:54,497 TWO YEARS TO THE DAY AND I WANT 3591 02:21:54,497 --> 02:21:56,399 TO GIVE AN UPDATE. 3592 02:21:56,399 --> 02:21:59,702 WE DON'T QUITE HAVE THE TWO YEAR 3593 02:21:59,702 --> 02:22:03,006 FOLLOW UP AND IS COMING NEXT 3594 02:22:03,006 --> 02:22:05,008 WEEK FOR EXAMS. 3595 02:22:05,008 --> 02:22:07,343 UP THROUGH MONTH 21 THIS IS WHAT 3596 02:22:07,343 --> 02:22:11,080 HER PARAMETERS LOOK LIKE. 3597 02:22:11,080 --> 02:22:14,784 SHE HAD SLOW ENGRAFTMENT AND 3598 02:22:14,784 --> 02:22:17,220 REQUIRED PLATELET TRANSFUSIONS 3599 02:22:17,220 --> 02:22:22,158 THROUGH MONTH SIX AND 3600 02:22:22,158 --> 02:22:23,926 TRANSFUS 3601 02:22:23,926 --> 02:22:28,564 TRANSFUSIONS AND WAS STARTING ON 3602 02:22:28,564 --> 02:22:31,934 AN AGONIST INCREASINGLY USED TO 3603 02:22:31,934 --> 02:22:34,637 TREAT AND THAT IS CONTINUED FROM 3604 02:22:34,637 --> 02:22:40,443 DAY 108 TO APPROXIMATELY 320. 3605 02:22:40,443 --> 02:22:43,946 AFTER THE DISCONTINUATION HER 3606 02:22:43,946 --> 02:22:49,419 HEMOGLOBIN IS NOW STABLE AND THE 3607 02:22:49,419 --> 02:22:51,921 PLATELET COUNT HAS STILL 3608 02:22:51,921 --> 02:22:53,990 INCREASED BUT STILL NOT NORMAL. 3609 02:22:53,990 --> 02:22:55,858 THE WHITE BLOOD CELL COUNT IS 3610 02:22:55,858 --> 02:22:59,929 NORMAL AND HEALTHY AND DOESN'T 3611 02:22:59,929 --> 02:23:04,567 SHOW HYPERLEUKO CYTOSIS AND HER 3612 02:23:04,567 --> 02:23:07,737 GENE MARKING SHOWS SIGNIFICANT 3613 02:23:07,737 --> 02:23:10,373 INDELS AND SMALL PERCENTAGE OF 3614 02:23:10,373 --> 02:23:14,977 HDL BUT REMARKABLY AS THE 3615 02:23:14,977 --> 02:23:16,946 PRESENCE OF SMALL AMOUNT OF 3616 02:23:16,946 --> 02:23:20,650 HEMOGLOBIN A AND RESIDUAL AMOUNT 3617 02:23:20,650 --> 02:23:24,754 OF HEMOGLOBIN S AND AN 3618 02:23:24,754 --> 02:23:26,923 UNEXPECTED OUTCOME FROM A 3619 02:23:26,923 --> 02:23:30,760 PROCESS DESIGN TO CREATE HEME 3620 02:23:30,760 --> 02:23:30,960 ZBLOEB -- 3621 02:23:33,663 --> 02:23:37,366 HEMOGLOBIN A NOT F AND WHEN WE 3622 02:23:37,366 --> 02:23:40,403 PUT THE LABORATORY VALUES 3623 02:23:40,403 --> 02:23:43,940 TOGETHER LOW HC HER PICTURE IS 3624 02:23:43,940 --> 02:23:49,879 CONSISTENT WITH A TRANSFUSION 3625 02:23:49,879 --> 02:23:55,918 INDEPENDENT OF THE FETAL 3626 02:23:55,918 --> 02:23:59,088 HEMOGLOBIN AND WE TOOK THIS FROM 3627 02:23:59,088 --> 02:24:00,590 DIFFERENT GENE EDITING PROGRAMS 3628 02:24:00,590 --> 02:24:04,026 AND THIS IS UNIQUELY CREATING 3629 02:24:04,026 --> 02:24:07,196 LOW HEMOGLOBIN S WHICH 3630 02:24:07,196 --> 02:24:08,531 HIGHLIGHTS ARE KEY FEATURES OF 3631 02:24:08,531 --> 02:24:09,665 THE DECREASE OF THE SYMPTOMS OF 3632 02:24:09,665 --> 02:24:20,009 SICKLE CELL DISEASE. 3633 02:24:32,021 --> 02:24:34,123 WE SEE MULTIDIRECTIVE REPAIR 3634 02:24:34,123 --> 02:24:36,792 FROM THE AC DONOR TEMPLATE AND 3635 02:24:36,792 --> 02:24:39,428 THAT'S HERE BUT WE ALSO SEE AND 3636 02:24:39,428 --> 02:24:41,664 THIS HAS BEEN DESCRIBED BY 3637 02:24:41,664 --> 02:24:51,941 SEVERAL DIFFERENT GROUPS IS A 3638 02:24:51,941 --> 02:24:54,610 PATCH OF THE DELTA HEMOGLOBIN 3639 02:24:54,610 --> 02:24:57,847 INTO THE BETA HEMOGLOBIN GENE 3640 02:24:57,847 --> 02:25:00,816 WHICH REVERTS THE SICKLE CELL 3641 02:25:00,816 --> 02:25:02,118 MUTATION BUT ADDS A COUPLE 3642 02:25:02,118 --> 02:25:05,421 ADDITIONAL AMINO ACID CHANGES. 3643 02:25:05,421 --> 02:25:09,258 SO IF WE LOOK AT THE ALLELE 3644 02:25:09,258 --> 02:25:14,263 FREQUENCIES OVER TIME WHAT WE 3645 02:25:14,263 --> 02:25:18,668 SEE IS FIRST OF ALL A SORT OF 3646 02:25:18,668 --> 02:25:20,903 DECLINE IN VARIOUS ALLELE 3647 02:25:20,903 --> 02:25:23,839 FREQUENCIES AND THEN AROUND 3648 02:25:23,839 --> 02:25:27,910 MONTH SIX WE SEE THE SLOW 3649 02:25:27,910 --> 02:25:31,881 INCREASE OF THE MINUS 2 DELETION 3650 02:25:31,881 --> 02:25:37,853 IN THE BETA GLOBIN GENE AND 3651 02:25:37,853 --> 02:25:44,193 INCREASE FROM MONTH SIX TO MONTH 3652 02:25:44,193 --> 02:25:46,629 21. 3653 02:25:46,629 --> 02:25:51,067 SORRY, YEAH, MONTH 12 AND SINCE 3654 02:25:51,067 --> 02:25:55,438 THAT TIME SLOWED AND I FORGOT TO 3655 02:25:55,438 --> 02:25:56,672 COMMENT ON THE PREVIOUS SLIDE BY 3656 02:25:56,672 --> 02:25:59,875 MONTH SIX WE DETECTED A SPLICE 3657 02:25:59,875 --> 02:26:03,746 SITE VARIANT IN THE B CORE GENE 3658 02:26:03,746 --> 02:26:08,618 AND THAT HAS INCREASED AS WELL. 3659 02:26:08,618 --> 02:26:13,856 IT SEEMS THAT WHETHER IT WAS A 3660 02:26:13,856 --> 02:26:16,492 DRIVER OR THE INEFFECTIVE 3661 02:26:16,492 --> 02:26:17,727 HEMATOPOIESIS WE SELECTED FOR 3662 02:26:17,727 --> 02:26:19,595 THE CLONE. 3663 02:26:19,595 --> 02:26:20,997 THE CLONE HAS NOW SLOWLY DRIFTED 3664 02:26:20,997 --> 02:26:26,535 DOWN OVER TIME AND WITH THAT 3665 02:26:26,535 --> 02:26:33,009 CLONE DRIFTING DOWN AND TO THE 3666 02:26:33,009 --> 02:26:39,315 REPAIR CLONES ARE DECREASING AND 3667 02:26:39,315 --> 02:26:41,183 HOPEFULLY WE'LL SEE THE DECLINE 3668 02:26:41,183 --> 02:26:47,957 DRIVEN BY B CLOR WITH A MORE 3669 02:26:47,957 --> 02:26:52,628 POLY CLONAL HEMATOPOIESIS AND 3670 02:26:52,628 --> 02:26:55,064 SIMILAR TO A PATIENT TREATED IN 3671 02:26:55,064 --> 02:26:58,167 WHICH A CLONE AN INTEGRATION 3672 02:26:58,167 --> 02:27:01,003 SITE SLOWLY DISSIPATED OVER 3673 02:27:01,003 --> 02:27:02,438 TIME. 3674 02:27:02,438 --> 02:27:04,640 AGAIN, NO WAY TO KNOW WHAT WILL 3675 02:27:04,640 --> 02:27:09,412 HAPPEN IN THIS PATIENT. 3676 02:27:09,412 --> 02:27:15,918 SO WE LEARNED THAT WE COULD SEE 3677 02:27:15,918 --> 02:27:18,120 ENGRAFTMENT OF THE CELLS AND IT 3678 02:27:18,120 --> 02:27:19,722 WAS SLOW BUT SHE IS NOW 3679 02:27:19,722 --> 02:27:21,223 CONTINUING TO DO CLINICALLY 3680 02:27:21,223 --> 02:27:21,424 WELL. 3681 02:27:21,424 --> 02:27:24,694 SO WHAT DO WE NEED TO DO TO 3682 02:27:24,694 --> 02:27:26,228 IMPROVE THE HDR PROCESS SO THE 3683 02:27:26,228 --> 02:27:27,930 OUTCOMES IN THE NEXT PATIENTS 3684 02:27:27,930 --> 02:27:29,732 MAY BE BETTER? 3685 02:27:29,732 --> 02:27:34,904 ONE OF THE THINGS WE'LL DISCOVER 3686 02:27:34,904 --> 02:27:38,808 OR HIGHLIGHTED BETWEEN THE BEGIN 3687 02:27:38,808 --> 02:27:42,778 INITIATION OF THE CLINICAL TRIAL 3688 02:27:42,778 --> 02:27:45,481 IS THE DONOR TEMPLATE HIGHLY 3689 02:27:45,481 --> 02:27:46,749 EFFECTIVE IN GETTING IT IN THE 3690 02:27:46,749 --> 02:27:50,720 CELLS THE NATURE OF THE GENOME 3691 02:27:50,720 --> 02:27:55,925 ACTIVATES THE H53 RESPONSE. 3692 02:27:55,925 --> 02:27:59,895 WE USED THE AAV2500 RESULTS IN 3693 02:27:59,895 --> 02:28:02,898 ABOUT 200 OF AAV GENOMES IN 3694 02:28:02,898 --> 02:28:05,201 CELLS ON AVERAGE. 3695 02:28:05,201 --> 02:28:09,505 WHEN WE REDUCE THE AAV TO 625 3696 02:28:09,505 --> 02:28:12,575 THE NUMBER OF VECTOR GENOMES PER 3697 02:28:12,575 --> 02:28:17,546 CELL DECREASES TO 50 AND THERE'S 3698 02:28:17,546 --> 02:28:18,981 A DIRECT DOSE RESPONSE BETWEEN 3699 02:28:18,981 --> 02:28:21,550 P21 THE DOWN STREAM TARGET OF 3700 02:28:21,550 --> 02:28:23,352 P53 AND THE AMOUNT OF VECTOR 3701 02:28:23,352 --> 02:28:23,719 GENOMES. 3702 02:28:23,719 --> 02:28:26,956 ONE CAN SEE IF WE COULD GET THE 3703 02:28:26,956 --> 02:28:28,624 VECTOR GENOME IN THE CELL TO A 3704 02:28:28,624 --> 02:28:31,927 MUCH LOWER AMOUNT WE MAY BE ABLE 3705 02:28:31,927 --> 02:28:34,630 TO IMPROVE THE CELL QUALITY THAT 3706 02:28:34,630 --> 02:28:35,798 IS TRANSPLANTED IN THE PATIENTS. 3707 02:28:35,798 --> 02:28:42,772 SO HOW CAN WE DO THAT? 3708 02:28:42,772 --> 02:28:46,542 SO ONE MECHANISM IS TO USE A 3709 02:28:46,542 --> 02:28:53,816 SMALL MOLECULE TO INHIBIT THE 3710 02:28:53,816 --> 02:28:57,953 CANONICAL PATHWAY AND THIS WAS 3711 02:28:57,953 --> 02:28:59,088 PUBLISHED BY OUR GROUP LAST YEAR 3712 02:28:59,088 --> 02:29:01,290 BUT I WANT TO SWITCH TO AN 3713 02:29:01,290 --> 02:29:04,026 ALTERNATIVE MECHANISM WHICH IS 3714 02:29:04,026 --> 02:29:12,735 SHOWN IN THE NEXT SLIDE. 3715 02:29:12,735 --> 02:29:15,938 WHICH WAS FIRST DESCRIBED SHOWED 3716 02:29:15,938 --> 02:29:16,005 A 3717 02:29:16,672 --> 02:29:24,079 DNA PLASMID INHIBITING THE 53BP1 3718 02:29:24,079 --> 02:29:30,286 AROUND THE SITE OF A DOUBLE 3719 02:29:30,286 --> 02:29:34,723 STRANDED BREAK AND THOUGHT THE 3720 02:29:34,723 --> 02:29:38,727 BLOCK OF THE ABILITY TO DO HDR. 3721 02:29:38,727 --> 02:29:41,797 THROUGH PRIOR WORK WE FELT USING 3722 02:29:41,797 --> 02:29:44,433 AN mRNA OR TRANSFECTION WAS NOT 3723 02:29:44,433 --> 02:29:47,236 GOING TO BE A VIABLE APPROACH IN 3724 02:29:47,236 --> 02:29:48,771 CD 34 CELLS TO MAINTAIN THAT 3725 02:29:48,771 --> 02:29:53,476 CELL HEALTH. 3726 02:29:53,476 --> 02:29:55,411 SO WE SWITCHED TO DELIVERING THE 3727 02:29:55,411 --> 02:29:57,246 SAME MOLECULE THAT HAS A PEPTIDE 3728 02:29:57,246 --> 02:30:01,917 GIVEN OUR SUCCESSES WITH 3729 02:30:01,917 --> 02:30:04,320 DELIVERING CAS 9 COLLABORATED 3730 02:30:04,320 --> 02:30:06,922 AND SHOWED WE COULD GET MAINTAIN 3731 02:30:06,922 --> 02:30:11,961 A HIGH FREQUENCY OF HDR BY 3732 02:30:11,961 --> 02:30:14,763 ADDING A PEPTIDE BUT ABLE TO 3733 02:30:14,763 --> 02:30:18,734 DECREASE THE MOI BY FOURFOLD. 3734 02:30:18,734 --> 02:30:22,171 AND WHAT YOU SEE IS ALONG THE Y 3735 02:30:22,171 --> 02:30:25,307 AXIS WITH THE PEPTIDE WE WERE 3736 02:30:25,307 --> 02:30:26,408 ABLE TO GENERATE HIGH 3737 02:30:26,408 --> 02:30:29,478 FREQUENCIES OF HDR AND ALONG THE 3738 02:30:29,478 --> 02:30:33,315 X AXIS THE PERCENT USED IN THE 3739 02:30:33,315 --> 02:30:35,951 ORIGINAL PROCESS WAS ABOUT 50% 3740 02:30:35,951 --> 02:30:39,822 TO 60% OF UNMODIFIED CELLS NOW 3741 02:30:39,822 --> 02:30:42,591 WITH A LOWER MOI IS 100% OF THE 3742 02:30:42,591 --> 02:30:43,859 UNMODIFIED CELLS. 3743 02:30:43,859 --> 02:30:46,295 WE INCREASED AND MAINTAINED OR 3744 02:30:46,295 --> 02:30:48,397 EVEN INCREASED THE HPR FREQUENCY 3745 02:30:48,397 --> 02:30:50,966 BUT INCREASED THE CELL HEALTH AS 3746 02:30:50,966 --> 02:30:58,340 MEASURED THROUGH CFUs. 3747 02:30:58,340 --> 02:31:02,077 SO I'M GOING TO -- THIS IS A 3748 02:31:02,077 --> 02:31:04,647 TABLE OUTLINING THE VARIOUS 3749 02:31:04,647 --> 02:31:08,050 CRITICAL ATTRIBUTES WE NOW 3750 02:31:08,050 --> 02:31:11,954 ACHIEVED AT CLINICAL SCALE 3751 02:31:11,954 --> 02:31:13,255 MANUFACTURING AND YOU CAN SEE 3752 02:31:13,255 --> 02:31:15,925 THAT THERE'S AN IMPROVEMENT IN 3753 02:31:15,925 --> 02:31:17,593 QUALITY FORMATION AND 3754 02:31:17,593 --> 02:31:20,195 IMPROVEMENT IN THE NUMBER OF 3755 02:31:20,195 --> 02:31:25,067 CLONES IN THE CFU ASSAY WITH AT 3756 02:31:25,067 --> 02:31:26,635 LEAST ONE ALLELE CORRECTED AN 3757 02:31:26,635 --> 02:31:30,205 THIS DATA SHOWN AS A TABLE WE 3758 02:31:30,205 --> 02:31:31,040 REDUCED THE MANUFACTURING TIME 3759 02:31:31,040 --> 02:31:34,610 FROM FIVE DAYS TO THREE DAYS AND 3760 02:31:34,610 --> 02:31:35,844 INCREASED THE CELL CORRECTION TO 3761 02:31:35,844 --> 02:31:40,349 75% AND INCREASED THE NUMBER OF 3762 02:31:40,349 --> 02:31:43,986 CFUs AND QUALITATIVELY THEY 3763 02:31:43,986 --> 02:31:49,291 APPEAR LARGER AND REDUCE THE 3764 02:31:49,291 --> 02:31:53,629 COST OF GOODS TO JUST VERY VERY 3765 02:31:53,629 --> 02:31:55,931 LARGE 450,000. 3766 02:31:55,931 --> 02:32:05,107 JUST TO SHOW WE CONTINUE TO MAKE 3767 02:32:05,107 --> 02:32:06,008 IMPROVEMENTS. 3768 02:32:06,008 --> 02:32:07,743 AGAIN, VISUALLY TO SHOW THE 3769 02:32:07,743 --> 02:32:09,511 DIFFERENCE BETWEEN THE VERSION 1 3770 02:32:09,511 --> 02:32:11,880 AND 2 WE'RE INCREASING OUR 3771 02:32:11,880 --> 02:32:14,750 ALLELE AND NUMBER OF COLONIES 3772 02:32:14,750 --> 02:32:19,188 THAT HAVE AT LEAST ONE ALLELE 3773 02:32:19,188 --> 02:32:24,193 CORRECTED AND WE'RE DECREASING 3774 02:32:24,193 --> 02:32:27,296 THE NUMBERS WITH THE EQUIVALENT 3775 02:32:27,296 --> 02:32:28,897 NUMBER TO ONE LESS THAN 20% IN 3776 02:32:28,897 --> 02:32:34,403 THE MANUFACTURING PROCESS. 3777 02:32:34,403 --> 02:32:37,973 SO THE IS NOW OPEN WITH THE NEW 3778 02:32:37,973 --> 02:32:38,741 MANUFACTURING PROCESS AT 3779 02:32:38,741 --> 02:32:39,541 STANFORD. 3780 02:32:39,541 --> 02:32:45,014 YOU CAN EITHER CONTACT STANFORD 3781 02:32:45,014 --> 02:32:49,084 DIRECTLY OR OUR STUDY CONTACT 3782 02:32:49,084 --> 02:32:51,920 JENNI HERBER AND IT WILL SOON BE 3783 02:32:51,920 --> 02:32:53,288 OPEN AT WASHINGTON UNIVERSITY 3784 02:32:53,288 --> 02:32:55,758 AND HOPING TO OPEN AT NATIONWIDE 3785 02:32:55,758 --> 02:32:58,661 CHILDREN'S HOSPITAL IN 2025. 3786 02:32:58,661 --> 02:33:00,729 SO THANK YOU AGAIN FOR THE 3787 02:33:00,729 --> 02:33:02,264 OPPORTUNITY TO SPEAK. 3788 02:33:02,264 --> 02:33:04,099 AS EVERYONE HAS HIGHLIGHTED THIS 3789 02:33:04,099 --> 02:33:05,634 IS TEAM SCIENCE THAT TAKES MORE 3790 02:33:05,634 --> 02:33:07,770 THAN A VILLAGE. 3791 02:33:07,770 --> 02:33:11,206 IT TAKES MAYBE A SMALL CITY, 3792 02:33:11,206 --> 02:33:18,080 MAYBE RENO TO DO THIS. 3793 02:33:18,080 --> 02:33:20,949 I WANT TO HIGHLIGHT WE WOULD 3794 02:33:20,949 --> 02:33:23,252 HAVE NEVER HAVE GOTTEN OFF THE 3795 02:33:23,252 --> 02:33:24,486 GROUND WITHOUT THE CARE SICKLE 3796 02:33:24,486 --> 02:33:25,187 CELL DISEASE INITIATIVE AND 3797 02:33:25,187 --> 02:33:26,889 FINALLY I'LL END WITH A PICTURE 3798 02:33:26,889 --> 02:33:28,657 OF THE PEOPLE IN MY LAB WOULD 3799 02:33:28,657 --> 02:33:31,226 CONTRIBUTED TO THE PROCESS. 3800 02:33:31,226 --> 02:33:41,570 THANK YOU VERY MUCH. 3801 02:33:42,971 --> 02:33:46,075 >> NO QUESTIONS. 3802 02:33:46,075 --> 02:33:47,810 >> I'M FROM THE UNIVERSITY OF 3803 02:33:47,810 --> 02:33:48,043 TORONTO. 3804 02:33:48,043 --> 02:33:49,745 YOU MENTIONED YOU WANT TO TALK 3805 02:33:49,745 --> 02:33:54,983 ABOUT THE HUMAN FETAL HEMOGLOBIN 3806 02:33:54,983 --> 02:33:56,685 ELEVATION BUT WASN'T SURE IF YOU 3807 02:33:56,685 --> 02:33:58,654 TALKED ABOUT IT. 3808 02:33:58,654 --> 02:34:01,190 >> SO, IT'S STILL A BIT OF A 3809 02:34:01,190 --> 02:34:02,991 MYSTERY TO US WHY IT'S SO HIGH. 3810 02:34:02,991 --> 02:34:04,059 IT'S CLEARLY COMING FROM A CLONE 3811 02:34:04,059 --> 02:34:08,931 I WOULD HAVE PREDICTED AHEAD OF 3812 02:34:08,931 --> 02:34:10,699 TIME SHOULD HAVE A MUTATION IN 3813 02:34:10,699 --> 02:34:14,703 BOTH ALLELES. 3814 02:34:14,703 --> 02:34:19,308 SOMEHOW THAT CLONE IS CAUSING 3815 02:34:19,308 --> 02:34:19,908 SOME FETAL HEMOGLOBIN 3816 02:34:19,908 --> 02:34:23,245 UPREGULATION NOT TO MAKE A FULLY 3817 02:34:23,245 --> 02:34:28,984 HEALTHY RED BLOOD CELL. 3818 02:34:28,984 --> 02:34:32,421 WHETHER IT'S BECAUSE THE 3819 02:34:32,421 --> 02:34:33,522 TRANSPLANT FETAL HEMOGLOBIN WAS 3820 02:34:33,522 --> 02:34:38,427 8% SO IT'S NOT LIKE SHE HAD HPF8 3821 02:34:38,427 --> 02:34:44,032 WHETHER THERE'S A CRYPTIC FETAL 3822 02:34:44,032 --> 02:34:45,968 HEMOGLOBIN POLYMORPHISM WE WANT 3823 02:34:45,968 --> 02:34:48,103 TO UNDERSTAND AND WILL DO THAT 3824 02:34:48,103 --> 02:34:51,306 FIRST BY DOING WHOLE GENOME 3825 02:34:51,306 --> 02:34:52,841 SEQUENCING AND WORK OUR WAY 3826 02:34:52,841 --> 02:34:55,310 THROUGH THE VARIOUS HYPOTHESES 3827 02:34:55,310 --> 02:34:56,912 BUT VERY INTERESTED IN ANYONE 3828 02:34:56,912 --> 02:34:57,479 HAVING IDEAS. 3829 02:34:57,479 --> 02:35:00,215 >> YOU MENTIONED THE CLONE. 3830 02:35:00,215 --> 02:35:03,051 BEFORE YOU MENTIONED THE CLONE I 3831 02:35:03,051 --> 02:35:06,455 THOUGHT IT WAS SLOWING OF THE 3832 02:35:06,455 --> 02:35:09,024 CYCLING AND A LAB HAS SHOWN YOU 3833 02:35:09,024 --> 02:35:14,029 CAN INCREASE FETAL HEMOGLOBIN. 3834 02:35:14,029 --> 02:35:17,266 >> SO WE HAVEN'T DONE ANY DIRECT 3835 02:35:17,266 --> 02:35:18,333 MEASURES OF CELL CYCLE. 3836 02:35:18,333 --> 02:35:21,470 WHAT I WILL SAY IS THE MARROW 3837 02:35:21,470 --> 02:35:23,872 WENT FROM LESS THAN 5% CELLULAR 3838 02:35:23,872 --> 02:35:27,042 TO FULLY CELLULAR AND THE FETAL 3839 02:35:27,042 --> 02:35:34,683 HEMOGLOBIN CAME UP AT THE SAME 3840 02:35:34,683 --> 02:35:45,093 TIME CERTAINLY STRESSED 3841 02:36:01,910 --> 02:36:02,211 ERYTHROEPOIESIS. 3842 02:36:02,211 --> 02:36:07,950 >> OUR NEXT TALK IS AGAIN 3843 02:36:07,950 --> 02:36:15,958 VIRTUAL FYODOR URNOV CRISPR 3844 02:36:15,958 --> 02:36:18,727 CURES FOR HEMOGLOBINOPATHY A 3845 02:36:18,727 --> 02:36:19,595 VIEW TO 2034. 3846 02:36:19,595 --> 02:36:22,931 >> THANK YOU FOR THE INVITATION. 3847 02:36:22,931 --> 02:36:24,266 HERE ARE MY DISCLOSURES. 3848 02:36:24,266 --> 02:36:27,769 I KNEW I'D BE THE LAST ONE 3849 02:36:27,769 --> 02:36:28,704 BEFORE LUNCH AND THEREFORE I'M 3850 02:36:28,704 --> 02:36:32,808 GOING TO GIVE A SHORT TALK WHICH 3851 02:36:32,808 --> 02:36:34,343 WILL NOT HAVE A LOT OF DATA 3852 02:36:34,343 --> 02:36:36,211 DENSE SLIDES BUT WANT TO LEAVE 3853 02:36:36,211 --> 02:36:39,615 YOU WITH A SENSE OF URGENCY. 3854 02:36:39,615 --> 02:36:42,150 I THINK WE HAVE A BIT OF A 3855 02:36:42,150 --> 02:36:44,720 CRISIS IN THE GENE EDITING FIELD 3856 02:36:44,720 --> 02:36:46,889 IN HELPING FOLKS AND I'D LIKE TO 3857 02:36:46,889 --> 02:36:52,694 OFFER A POTENTIAL PATH FORWARD. 3858 02:36:52,694 --> 02:36:54,830 DAN BAUER AND I DID NOT 3859 02:36:54,830 --> 02:36:56,498 COORDINATE AND THAT SAID I'LL 3860 02:36:56,498 --> 02:36:58,700 START THE TALK THE SAME WAY. 3861 02:36:58,700 --> 02:37:07,943 OUR VIEW TO 2034 IS INFORMED BY 3862 02:37:07,943 --> 02:37:10,245 THE COGNITIVE DISSONANCE OF 3863 02:37:10,245 --> 02:37:13,582 WHERE THEY'RE WORKING AND WHERE 3864 02:37:13,582 --> 02:37:21,590 THE PUBLIC HEALTH CHALLENGESS 3865 02:37:21,590 --> 02:37:22,391 LIE. 3866 02:37:22,391 --> 02:37:25,827 GENE EDITING HAS A THREE DECADE 3867 02:37:25,827 --> 02:37:27,162 HISTORY AND BY FOLKS MENTIONED 3868 02:37:27,162 --> 02:37:31,566 AT THE BOTTOM OF THE SLIDE. 3869 02:37:31,566 --> 02:37:32,634 I'M GOING TO EXTRAPOLATE FROM 3870 02:37:32,634 --> 02:37:34,202 THE PAST WHICH IS THE ONE WAY WE 3871 02:37:34,202 --> 02:37:35,671 KNOW HOW TO DO THIS IN LOOKING 3872 02:37:35,671 --> 02:37:38,173 TO THE DECADE AHEAD AND IN 3873 02:37:38,173 --> 02:37:41,209 PARTICULAR HIGHLIGHT A PROFOUND 3874 02:37:41,209 --> 02:37:49,818 CHALLENGE WE AS A COMMUNITY ARE 3875 02:37:49,818 --> 02:37:52,387 EXPERIENCING. 3876 02:37:52,387 --> 02:37:53,755 EXACEL MANUFACTURE HAS 3877 02:37:53,755 --> 02:37:58,627 PROGENITOR CELLS USING THE 3878 02:37:58,627 --> 02:38:01,596 PROTEIN PARTICLE AND IN THE RNA 3879 02:38:01,596 --> 02:38:04,733 DAN BAUER DESCRIBED AND WE HAVE 3880 02:38:04,733 --> 02:38:07,402 200 MILLION IN WHICH THERE'S A 3881 02:38:07,402 --> 02:38:13,775 PROTEIN CREATING A DOUBLE STRAND 3882 02:38:13,775 --> 02:38:14,743 BREAK. 3883 02:38:14,743 --> 02:38:17,379 THE SUBJECT UNDER GOES 3884 02:38:17,379 --> 02:38:18,580 CONDITIONING IN THE CELLS. 3885 02:38:18,580 --> 02:38:22,050 I WANT TO HIGHLIGHT TWO KEY 3886 02:38:22,050 --> 02:38:23,986 PERFORMANCE METHODS OF THE 3887 02:38:23,986 --> 02:38:28,757 PROTEIN PARTICLE AND GUIDE RNA 3888 02:38:28,757 --> 02:38:32,260 AS IT GOES TO HEMOGLOBINOPATHY 3889 02:38:32,260 --> 02:38:38,166 AND THE PHARMACEUTICALS AND YOU 3890 02:38:38,166 --> 02:38:39,935 SEE THE SOME TOTAL OF CANDIDATE 3891 02:38:39,935 --> 02:38:43,138 OFF TARGET SITES FOR THE GUIDE 3892 02:38:43,138 --> 02:38:45,207 RNA IN THE HUMAN GENOME. 3893 02:38:45,207 --> 02:38:55,717 YOU CAN SEE NORTH OF 5,000 SITES 3894 02:38:55,717 --> 02:38:59,921 AND TARGET SITES. 3895 02:38:59,921 --> 02:39:05,127 IN A LARGE NUMBER OF EDITED WORK 3896 02:39:05,127 --> 02:39:08,563 LOOKING AT ALL THE OFF TARGET 3897 02:39:08,563 --> 02:39:11,600 SITES NO TARGETING WAS DETECTED 3898 02:39:11,600 --> 02:39:13,402 THAT IS AN IMPRESSIVE OUTCOME 3899 02:39:13,402 --> 02:39:17,706 FOR GENE EDITING. 3900 02:39:17,706 --> 02:39:19,908 STAYING IN MY NARROW LANE OF 3901 02:39:19,908 --> 02:39:21,877 GENE EDITING IN ADDITION TO THE 3902 02:39:21,877 --> 02:39:25,514 OR TARGET ISSUES THERE WAS 3903 02:39:25,514 --> 02:39:25,881 TRANSPLANTATION. 3904 02:39:25,881 --> 02:39:26,615 THIS IS DATA PRESENTED AND WHAT 3905 02:39:26,615 --> 02:39:37,159 YOU SEE AT THE TOP IS EDITING IN 3906 02:39:37,926 --> 02:39:39,928 THE ENHANCER MENTIONED AND THE 3907 02:39:39,928 --> 02:39:43,331 EDITING AT THE TARGET IN THE 3908 02:39:43,331 --> 02:39:44,800 BONE MARROW OF THE TARGET IS 3909 02:39:44,800 --> 02:39:46,401 FLAT. 3910 02:39:46,401 --> 02:39:52,074 IN THE BOTTOM YOU SEE IN THE 3911 02:39:52,074 --> 02:39:55,944 LARGER NUMBER THE INDEL 3912 02:39:55,944 --> 02:39:57,446 EFFICIENCY STAYS FLAT OVER TIME. 3913 02:39:57,446 --> 02:40:04,386 THE EDITED CELLS ONCE THEY 3914 02:40:04,386 --> 02:40:06,655 ENGRAFT PROVIDE STABLE 3915 02:40:06,655 --> 02:40:10,358 HEMATOPOIETIC CONDITION AND IN 3916 02:40:10,358 --> 02:40:15,530 TERMS OF THEIR SYMPTOMS OF 3917 02:40:15,530 --> 02:40:18,333 SICKLE CELL DISEASE IS MORE 3918 02:40:18,333 --> 02:40:21,303 SUCCESSFUL AND HERE I AM AT TO 3919 02:40:21,303 --> 02:40:26,374 THE GENE EDITOR AND HERE'S WHAT 3920 02:40:26,374 --> 02:40:28,110 I CAN OFFER. 3921 02:40:28,110 --> 02:40:31,446 THE ON-TARGET EFFICIENCY OF GENE 3922 02:40:31,446 --> 02:40:32,948 EDITING AT THERAPEUTIC CELL TYPE 3923 02:40:32,948 --> 02:40:35,951 OF CLINICAL SCALE PRODUCTION IS 3924 02:40:35,951 --> 02:40:39,955 AT, OR ABOVE THE THERAPEUTIC 3925 02:40:39,955 --> 02:40:46,728 THRESHOLD AND NO OFF-TARGET 3926 02:40:46,728 --> 02:40:50,265 CUTTING OBSERVED ABOVE THE LOD 3927 02:40:50,265 --> 02:40:55,604 IN THE LARGEST SUCH PANEL AND MY 3928 02:40:55,604 --> 02:40:59,274 SUMMARY CRISPR CAS 9 GENE 3929 02:40:59,274 --> 02:41:02,577 EDITING 1.0 HAS REDUCED AND MET 3930 02:41:02,577 --> 02:41:03,311 THE REQUIRED PERFORMANCE METRICS 3931 02:41:03,311 --> 02:41:08,650 TO DATE. 3932 02:41:08,650 --> 02:41:12,154 HOW IS THIS GOING? 3933 02:41:12,154 --> 02:41:15,757 VERTEX DISCLOSED THEY ENROLLED 3934 02:41:15,757 --> 02:41:21,630 20 PATIENTS TO BE TREATED AND 3935 02:41:21,630 --> 02:41:23,832 HERE COMES THE COGNITIVE 3936 02:41:23,832 --> 02:41:27,469 DISSONANCE WHAT DOES 20 PATIENTS 3937 02:41:27,469 --> 02:41:27,702 MEAN? 3938 02:41:27,702 --> 02:41:30,105 AND OBVIOUSLY THE LIMITING 3939 02:41:30,105 --> 02:41:34,409 FACTOR IS THE CELL CROSSING AND 3940 02:41:34,409 --> 02:41:35,477 TRANSPLANT AND OTHERS PURSUE 3941 02:41:35,477 --> 02:41:36,745 GENE EDITING FOR SICKLE CELL 3942 02:41:36,745 --> 02:41:40,582 DISEASE. 3943 02:41:40,582 --> 02:41:43,518 AND ONE HAS SHOWED IMPRESSIVE 3944 02:41:43,518 --> 02:41:47,522 DATA USING A DIFFERENT NUCLEASE 3945 02:41:47,522 --> 02:41:49,691 CAS 12A AND THE DOUBLE STRAND 3946 02:41:49,691 --> 02:41:52,527 BREAK MAKING OUTSTANDING 3947 02:41:52,527 --> 02:41:55,230 CLINICAL DATA AND THE 3948 02:41:55,230 --> 02:41:55,864 MANUFACTURING PROCESS EX VIVO 3949 02:41:55,864 --> 02:42:00,235 AND TRANSPLANT IS THE SAME. 3950 02:42:00,235 --> 02:42:05,540 THE PATH TO MAKING A GLOBAL 3951 02:42:05,540 --> 02:42:07,943 IMPACT WILL HAVE TO COME FROM 3952 02:42:07,943 --> 02:42:11,947 THE SYNERGISTIC INTERPLAY OF 3953 02:42:11,947 --> 02:42:14,382 FOUR THINGS. 3954 02:42:14,382 --> 02:42:17,819 EDITING INNOVATION, IN VIVO 3955 02:42:17,819 --> 02:42:19,020 DELIVERY AND REDUCTION OR 3956 02:42:19,020 --> 02:42:21,823 ELIMINATION OF CONDITIONING AND 3957 02:42:21,823 --> 02:42:24,326 CLINICAL TRACT. 3958 02:42:24,326 --> 02:42:25,627 I'LL SPEAK TO EVERYTHING OUTSIDE 3959 02:42:25,627 --> 02:42:30,265 CONDITIONING I DON'T WANT TO 3960 02:42:30,265 --> 02:42:32,534 SPEAK ABOUT CONDITIONING. 3961 02:42:32,534 --> 02:42:36,738 WHO CAN SPEAK ABOUT AND I CAN'T. 3962 02:42:36,738 --> 02:42:38,406 LET ME SPEAK ABOUT THE CLINICAL 3963 02:42:38,406 --> 02:42:39,741 TRACK RECORD BECAUSE I THINK 3964 02:42:39,741 --> 02:42:42,777 IT'S RELEVANT TO WHAT AS GENE 3965 02:42:42,777 --> 02:42:44,145 EDITORS SHOULD BE THINKING 3966 02:42:44,145 --> 02:42:45,480 ABOUT. 3967 02:42:45,480 --> 02:42:48,917 THESE ARE PUBLISHED DATA AND IN 3968 02:42:48,917 --> 02:42:51,920 THE STUDY THEY ARE USED NANO 3969 02:42:51,920 --> 02:42:53,755 PARTICLE DELIVERY IN VIVO AND 3970 02:42:53,755 --> 02:42:55,857 GUIDE RNA THAT TARGETS CAS 9 TO 3971 02:42:55,857 --> 02:42:59,694 A GENE CALLED ATTR. 3972 02:42:59,694 --> 02:43:03,498 IT'S SHOWN ON THE SCHEMATIC FROM 3973 02:43:03,498 --> 02:43:06,067 TO THE JOURNAL PAPER IT DELIVERS 3974 02:43:06,067 --> 02:43:08,803 THE mRNA TRANSLATED TO CAS 9 AND 3975 02:43:08,803 --> 02:43:10,739 IT GOES TO THE NUCLEUS AND 3976 02:43:10,739 --> 02:43:13,108 CREATES A DOUBLE STRAND BREAK 3977 02:43:13,108 --> 02:43:14,542 BUT IN A DIFFERENT GENE AND 3978 02:43:14,542 --> 02:43:16,544 SMALL INVERSIONS IN DELETIONS 3979 02:43:16,544 --> 02:43:17,545 AND WE HOPE THE SUBJECT 3980 02:43:17,545 --> 02:43:18,780 EXPERIENCED A REDUCTION IN THE 3981 02:43:18,780 --> 02:43:20,749 AMOUNT OF TOXIC PROTEIN IN THEIR 3982 02:43:20,749 --> 02:43:25,353 BLOODSTREAM. 3983 02:43:25,353 --> 02:43:27,422 AS AN EDITOR I CONTINUE TO WORRY 3984 02:43:27,422 --> 02:43:29,591 ABOUT THE TARGET SITES. 3985 02:43:29,591 --> 02:43:33,028 IT'S COMFORTING BUT NOT 3986 02:43:33,028 --> 02:43:34,195 COMPLETELY SATISFIED UNTIL WE 3987 02:43:34,195 --> 02:43:35,897 KNOW ABOUT THE LARGE PANEL OF 3988 02:43:35,897 --> 02:43:38,300 SUBJECTS ON THE CLINICAL TRIAL 3989 02:43:38,300 --> 02:43:39,701 BUT THERE ARE NOW CLINICAL DATA 3990 02:43:39,701 --> 02:43:44,172 FOR SPECIFICITY OF THIS GUIDE 3991 02:43:44,172 --> 02:43:46,408 FOR DIFFERENT EXPERIMENTS IS 3992 02:43:46,408 --> 02:43:48,243 QUITE COMPELLING. 3993 02:43:48,243 --> 02:43:52,280 THEY LOOKED AT A LARGE NUMBER OF 3994 02:43:52,280 --> 02:43:57,752 SITES AND SAW ZERO DETECTION. 3995 02:43:57,752 --> 02:44:01,956 TWO DIFFERENT TEAMS, TWO 3996 02:44:01,956 --> 02:44:05,327 DIFFERENT GUIDE RNAs AND ATTR 3997 02:44:05,327 --> 02:44:07,495 AND ON TARGET EFFICIENCY ROBUST 3998 02:44:07,495 --> 02:44:10,332 AND LOOKING AT TARGETS, NO 3999 02:44:10,332 --> 02:44:12,734 MEASURABLE TARGET CUTTING. 4000 02:44:12,734 --> 02:44:15,236 HOW ARE THE SUBJECTS DOING 4001 02:44:15,236 --> 02:44:15,537 CLINICALLY? 4002 02:44:15,537 --> 02:44:19,941 I'LL SHOW THE BIOMARKER IS THE 4003 02:44:19,941 --> 02:44:23,411 TOXIC PROTEIN SEVERAL COHORTS OF 4004 02:44:23,411 --> 02:44:27,916 SUBJECTS ON TO DIFFERENT 4005 02:44:27,916 --> 02:44:30,318 INDICATIONS AND WITHIN TWO 4006 02:44:30,318 --> 02:44:31,920 MONTHS OF DOSING THE GENE 4007 02:44:31,920 --> 02:44:33,221 THEY'RE TRYING TO KNOCK OUT GOES 4008 02:44:33,221 --> 02:44:34,155 DOWN TO JUST ABOUT THE LEVEL OF 4009 02:44:34,155 --> 02:44:39,928 DETECTION. 4010 02:44:39,928 --> 02:44:45,333 FORMIDABLE THE SUBJECT RESPONSE. 4011 02:44:45,333 --> 02:44:49,704 FOLKS, INTELIA IS DOING A 4012 02:44:49,704 --> 02:44:51,039 CLINICAL TRIAL WITH 765 SUBJECTS 4013 02:44:51,039 --> 02:44:52,640 WITH THIS APPROACH. 4014 02:44:52,640 --> 02:44:55,043 AS A GENE EDITOR AS I LOOK BACK 4015 02:44:55,043 --> 02:44:59,180 AT OUR 20 PLUS YEAR HISTORY IT'S 4016 02:44:59,180 --> 02:45:00,982 FORMIDABLE A TRIAL OF SUCH SIZE 4017 02:45:00,982 --> 02:45:03,952 IS ABOUT TO TAKE PLACE BUT 4018 02:45:03,952 --> 02:45:05,019 NOTABLY NOT FOR SICKLE CELL 4019 02:45:05,019 --> 02:45:10,058 DISEASE BUT FOR DOSES. 4020 02:45:10,058 --> 02:45:11,960 WITH RESPECT TO IN VIVO NON 4021 02:45:11,960 --> 02:45:18,633 VIRAL DELIVERY OF GENE EDITORING 4022 02:45:18,633 --> 02:45:21,703 A FORMIDABLE AMOUNT OF WORK IS 4023 02:45:21,703 --> 02:45:24,539 GOING AND THERE'S DIFFERENT GENE 4024 02:45:24,539 --> 02:45:26,841 EDITING BUT THE DELIVERY IS THE 4025 02:45:26,841 --> 02:45:28,777 SAME, LNP. 4026 02:45:28,777 --> 02:45:33,381 I MENTIONED VICTORIA GRAY SHOWN 4027 02:45:33,381 --> 02:45:39,354 HERE THE FIRST WITH THE EXACELL 4028 02:45:39,354 --> 02:45:41,089 ARE USING THIS AND THERE'S OTHER 4029 02:45:41,089 --> 02:45:44,592 TOOLS THAT DO NOT REQUIRE THE 4030 02:45:44,592 --> 02:45:45,794 CLASSICAL DOUBLE STRAND BREAK 4031 02:45:45,794 --> 02:45:47,829 AND THESE ARE ADVANCING TO THE 4032 02:45:47,829 --> 02:45:49,330 CLINICAL IN FACT SUBJECTS ARE 4033 02:45:49,330 --> 02:45:52,667 BEING DOSED AND THIS REALLY 4034 02:45:52,667 --> 02:45:54,202 UNDER LIES THE FACT AS DELIVERY 4035 02:45:54,202 --> 02:45:56,404 IMPROVES SO DOES THE EDITING 4036 02:45:56,404 --> 02:45:58,773 TOOLBOX AND IT'S MOVING TO THE 4037 02:45:58,773 --> 02:46:01,209 CLINIC. 4038 02:46:01,209 --> 02:46:03,812 WHY AM I TELLING YOU THIS? 4039 02:46:03,812 --> 02:46:08,650 WHAT IS THE RELEVANCE OF THE 4040 02:46:08,650 --> 02:46:11,453 EDITING THE RELEVANCE IS THE 4041 02:46:11,453 --> 02:46:11,853 LNP. 4042 02:46:11,853 --> 02:46:15,323 THERE WAS A LOVELY PAPER IN 4043 02:46:15,323 --> 02:46:17,325 SCIENCE MAYBE A MONTH AGO 4044 02:46:17,325 --> 02:46:22,764 DEMONSTRATING THAT LIPID NANO 4045 02:46:22,764 --> 02:46:24,799 PARTICLE DELIVERY TO 4046 02:46:24,799 --> 02:46:26,434 HEMATOPOIETIC STEM AND 4047 02:46:26,434 --> 02:46:28,236 PROGENITOR CELLS IS FEASIBLE AND 4048 02:46:28,236 --> 02:46:32,040 THE DATA ON THE RIGHT IS FROM A 4049 02:46:32,040 --> 02:46:33,775 BIOTECHNOLOGY COMPANY AND THEY 4050 02:46:33,775 --> 02:46:35,643 HAVE SHOWN A LIPID NANO PARTICLE 4051 02:46:35,643 --> 02:46:39,214 DELIVERY OF THE MESSENGER RNA TO 4052 02:46:39,214 --> 02:46:43,952 THE LT IN THE MARROW OF 4053 02:46:43,952 --> 02:46:46,521 HUMANIZED MICE AND CRITICALLY 4054 02:46:46,521 --> 02:46:50,959 NON-HUMAN PRIMATES AND LOOK AT 4055 02:46:50,959 --> 02:46:52,427 THE EFFICIENCY WITH WHICH THE 4056 02:46:52,427 --> 02:46:56,431 mRNA HAS BEEN DELIVERED. 4057 02:46:56,431 --> 02:47:00,802 BEFORE WE CELEBRATE LET ME 4058 02:47:00,802 --> 02:47:06,307 SPRINKLE A HEALTHY DOSE OF NOT 4059 02:47:06,307 --> 02:47:07,942 NEGATIVE NANCY BUT THERE'S DATA 4060 02:47:07,942 --> 02:47:10,778 BUT THEY HAD TO CUT THEIR 4061 02:47:10,778 --> 02:47:12,280 WORKFORCE AND I WILL EXPLAIN WHY 4062 02:47:12,280 --> 02:47:14,616 AND WHAT IMPLICATIONS THAT HAS 4063 02:47:14,616 --> 02:47:17,051 FOR OUR COMMUNITIES OF EDITOR 4064 02:47:17,051 --> 02:47:21,155 FOR THE HEMOGLOBINOPATHIES IN A 4065 02:47:21,155 --> 02:47:21,689 SECOND. 4066 02:47:21,689 --> 02:47:28,263 THE POSITIVE NEWS IS PEOPLE 4067 02:47:28,263 --> 02:47:34,769 ACTIVELY ACTING TO USE IN VIVO 4068 02:47:34,769 --> 02:47:39,841 NANO PARTICLE ENCAPSULATION AND 4069 02:47:39,841 --> 02:47:45,280 THIS PAST YEAR THEY DESCRIBED AN 4070 02:47:45,280 --> 02:47:47,949 INNOVATIVE APPROACH ON USING 4071 02:47:47,949 --> 02:47:54,689 GENE EDITING TO SHIELD THE 4072 02:47:54,689 --> 02:47:58,026 EDITED HEMATOPOIETIC STEM CELL 4073 02:47:58,026 --> 02:48:01,329 AND KEEP THE EDITED CELLS 4074 02:48:01,329 --> 02:48:03,031 INTACT. 4075 02:48:03,031 --> 02:48:04,566 A DIFFERENT BIO TECHNOLOGY 4076 02:48:04,566 --> 02:48:09,804 COMPANY HAS DISCLOSED AN ELEGANT 4077 02:48:09,804 --> 02:48:12,840 APPROACH AND IN SICKLE THEY'RE 4078 02:48:12,840 --> 02:48:17,445 PROPOSING WITH ONE EDITOR EDIT 4079 02:48:17,445 --> 02:48:20,415 THE MUTATION AND WITH THE SAME 4080 02:48:20,415 --> 02:48:21,983 CELL CREATE THE SHIELDING 4081 02:48:21,983 --> 02:48:24,085 MUTATION SUCH THAT WHEN THE 4082 02:48:24,085 --> 02:48:26,754 CELLS ARE TRANSPLANTED BACK YOU 4083 02:48:26,754 --> 02:48:31,225 CAN CONDITION THE PATIENT WITH 4084 02:48:31,225 --> 02:48:39,467 AN ANTIBODY AND HOW EXCITING. 4085 02:48:39,467 --> 02:48:42,537 WELL, THEY JUST HAD A MAJOR 4086 02:48:42,537 --> 02:48:44,706 WORKFORCE REDUCTION. 4087 02:48:44,706 --> 02:48:46,641 FOLKS, WRAPPING UP, I'VE TOLD 4088 02:48:46,641 --> 02:48:48,309 YOU THE PATH TO 2034 LIES 4089 02:48:48,309 --> 02:48:50,011 THROUGH THESE FOUR THINGS AND 4090 02:48:50,011 --> 02:48:50,612 I'VE GIVEN YOU THE FOLLOWING 4091 02:48:50,612 --> 02:48:55,450 EXAMPLES. 4092 02:48:55,450 --> 02:48:58,453 PEOPLE ARE ACTIVELY DEPLOYING 4093 02:48:58,453 --> 02:49:03,358 LNP DELIVERY OF CAS 9 IN VIVO TO 4094 02:49:03,358 --> 02:49:09,964 HSCs IN THE NON-HUMAN PRIMATES. 4095 02:49:09,964 --> 02:49:12,367 EDITING INNOVATION FROM 1.0 TO 4096 02:49:12,367 --> 02:49:15,136 2.0 TO 3.0 IS GROWING GIVING US 4097 02:49:15,136 --> 02:49:21,943 GENE EDITORS MORE OPTIONS HOW TO 4098 02:49:21,943 --> 02:49:22,176 CREATE. 4099 02:49:22,176 --> 02:49:24,712 ALL OF THIS IS HAPPENING AT THE 4100 02:49:24,712 --> 02:49:26,180 TIME WHEN LIPID NANO PARTICLE 4101 02:49:26,180 --> 02:49:28,750 DELIVERY OF THE EDITING 4102 02:49:28,750 --> 02:49:31,119 MODALITIES IS GROWING IN 4103 02:49:31,119 --> 02:49:31,953 CLINICAL SCALE. 4104 02:49:31,953 --> 02:49:33,688 IN THREE YEARS THEY'LL HAVE 4105 02:49:33,688 --> 02:49:35,657 COMPLETED THE PHASE 3. 4106 02:49:35,657 --> 02:49:43,364 THERE'LL BE MORE THAN 1,000 4107 02:49:43,364 --> 02:49:45,133 SUBJECTS DOSED AND IT WILL 4108 02:49:45,133 --> 02:49:47,101 PROVIDE INFORMATION IN TERMS OF 4109 02:49:47,101 --> 02:49:48,403 WHAT THE SAFETY PROFILE IS OF 4110 02:49:48,403 --> 02:49:53,474 THIS APPROACH AND FINALLY I 4111 02:49:53,474 --> 02:49:54,142 MENTIONED THE POTENTIAL FOR 4112 02:49:54,142 --> 02:49:58,279 DOUBLE EDITING TO REDUCE THE 4113 02:49:58,279 --> 02:49:59,514 CONDITION. 4114 02:49:59,514 --> 02:50:01,416 AND SO MY LAST SLIDE THANK YOU 4115 02:50:01,416 --> 02:50:02,650 FOR THE OPPORTUNITY TO SPEAK 4116 02:50:02,650 --> 02:50:05,920 WITH YOU IS THE FOLLOWING. 4117 02:50:05,920 --> 02:50:10,158 I MENTIONED WORKFORCE REDUCTION. 4118 02:50:10,158 --> 02:50:12,460 THERE'S NO SIMPLER WORD THAN IT 4119 02:50:12,460 --> 02:50:14,395 GRIEVES ME. 4120 02:50:14,395 --> 02:50:16,798 THAT OUR ENTIRE SECTOR IS 4121 02:50:16,798 --> 02:50:19,734 EXPERIENCING FROM A WORKFORCE 4122 02:50:19,734 --> 02:50:20,935 REDUCTION PERSPECTIVE WHAT ONE 4123 02:50:20,935 --> 02:50:22,470 LEADING SCIENTIST AT THE COMPANY 4124 02:50:22,470 --> 02:50:27,475 DESCRIBES AT QUOTE, A BLOOD BATH 4125 02:50:27,475 --> 02:50:29,877 IN PRACTICAL TERMS MY 4126 02:50:29,877 --> 02:50:30,845 PROFESSIONAL ASSESSMENT AS 4127 02:50:30,845 --> 02:50:32,613 SOMEBODY WHO FORTUNATELY IS ON 4128 02:50:32,613 --> 02:50:34,549 THE FIRST-NAME BASIS WITH MANY 4129 02:50:34,549 --> 02:50:37,018 LEADERS AT EVERY ONE OF THESE 4130 02:50:37,018 --> 02:50:39,821 BIO TECHS NOT ONE OF THE FOR 4131 02:50:39,821 --> 02:50:44,158 PROFIT ENTITIES WILL 4132 02:50:44,158 --> 02:50:46,127 AGGRESSIVELY GO OVER GENE 4133 02:50:46,127 --> 02:50:49,163 EDITING WHICH WOULD BE SCALABLE 4134 02:50:49,163 --> 02:50:53,334 TO THE GLOBAL CHALLENGE WHICH IS 4135 02:50:53,334 --> 02:50:54,268 THE MARKET CONDITIONS WILL 4136 02:50:54,268 --> 02:50:55,937 SIMPLY NOT ALLOW THEM TO DO THAT 4137 02:50:55,937 --> 02:50:58,372 IN THE NEXT FIVE YEARS. 4138 02:50:58,372 --> 02:51:04,345 LET ME END ON THE NOTE OF HOPE. 4139 02:51:04,345 --> 02:51:05,880 THE FEDERAL GOVERNMENT STEPPED 4140 02:51:05,880 --> 02:51:09,784 IN AND PROVIDED $140 MILLION TO 4141 02:51:09,784 --> 02:51:15,223 THE SOMATIC GENE EDITING 4142 02:51:15,223 --> 02:51:16,791 CONSORTIUM BUT NOT SICKLE. 4143 02:51:16,791 --> 02:51:18,960 IT'S NOT THEY MEANT TO EXCLUDE 4144 02:51:18,960 --> 02:51:20,628 SICKLE, IT'S NOT HOW THE PROGRAM 4145 02:51:20,628 --> 02:51:26,300 WAS CONFIGURED. 4146 02:51:26,300 --> 02:51:28,803 I THEREFORE WOULD POSE FOR THE 4147 02:51:28,803 --> 02:51:30,171 AUDIENCE THE QUESTION WHETHER 4148 02:51:30,171 --> 02:51:31,806 NOW IS THE TIME IN THE FIELD TO 4149 02:51:31,806 --> 02:51:34,809 LEVERAGE ALL THIS AMAZING 4150 02:51:34,809 --> 02:51:36,811 INNOVATION FROM DAN BAUER AND 4151 02:51:36,811 --> 02:51:38,212 MATT THAT EVERYONE HAS SPOKEN 4152 02:51:38,212 --> 02:51:39,180 ABOUT AND EVERYONE IN THE FIELD 4153 02:51:39,180 --> 02:51:41,816 HAS DEVELOPED TO HAVE US AS A 4154 02:51:41,816 --> 02:51:44,986 NATION STEP FORWARD WITH RESPECT 4155 02:51:44,986 --> 02:51:47,955 TO SUPPORTING AN ACCELERATED 4156 02:51:47,955 --> 02:51:52,593 PATH FOR GENE EDITING SOLUTION 4157 02:51:52,593 --> 02:51:54,061 SCALABLE FOR THE GLOBAL HEALTH 4158 02:51:54,061 --> 02:51:57,932 CHALLENGE BY 2034. 4159 02:51:57,932 --> 02:51:58,633 WHY DO THIS? 4160 02:51:58,633 --> 02:52:01,636 IN TERMS OF DESCRIBING HOW TO 4161 02:52:01,636 --> 02:52:04,572 ACT AND SHE SAID WE MUST MERGE 4162 02:52:04,572 --> 02:52:06,574 MERCY WITH MIGHT AND MIGHT WITH 4163 02:52:06,574 --> 02:52:06,774 RIGHT. 4164 02:52:06,774 --> 02:52:15,249 THANK YOU. 4165 02:52:15,249 --> 02:52:19,954 >> THANK YOU, DR. URNOV WITH THE 4166 02:52:19,954 --> 02:52:22,757 WONDERFUL SYSTEMS APPROACH. 4167 02:52:22,757 --> 02:52:23,024 QUESTIONS? 4168 02:52:23,024 --> 02:52:28,229 ANYBODY FROM THE AUDIENCE? 4169 02:52:28,229 --> 02:52:28,930 NONE. 4170 02:52:28,930 --> 02:52:31,933 SO YOU'VE BEEN VERY CLEAR IN 4171 02:52:31,933 --> 02:52:34,235 YOUR MESSAGE. 4172 02:52:34,235 --> 02:52:35,703 THANK YOU AGAIN FOR GIVING US 4173 02:52:35,703 --> 02:52:38,573 THE FUTURISTIC VIEW OF WHERE WE 4174 02:52:38,573 --> 02:52:40,041 SHOULD BE HEADING. 4175 02:52:40,041 --> 02:52:41,242 THANK YOU ALL AND THANK YOU FOR 4176 02:52:41,242 --> 02:52:41,776 ALL THE SPEAKERS FOR THE 4177 02:52:41,776 --> 02:52:43,778 SESSION. 4178 02:52:43,778 --> 02:52:46,881 AND SO LET'S TAKE A LUNCH BREAK 4179 02:52:46,881 --> 02:52:48,367 AND TRY TO BE BACK PROMPTLY HERE 4180 02:52:48,367 --> 02:52:49,468 GOOD AFTERNOON, EVERYBODY. 4181 02:52:49,468 --> 02:52:52,404 WE'RE GOING TO START WITH OUR 4182 02:52:52,404 --> 02:52:55,941 NEXT SESSION THAT IS UPDATES ON 4183 02:52:55,941 --> 02:52:57,843 IN THE SESSION BUT THE NEXT 4184 02:52:57,843 --> 02:52:59,645 COMPONENT OF THE SESSION 1 WHICH 4185 02:52:59,645 --> 02:53:03,082 IS UPDATES ON TRIALS ON SICKLE 4186 02:53:03,082 --> 02:53:03,615 CELL DISEASE. 4187 02:53:03,615 --> 02:53:06,218 SO THE FIRST TALK IS GOING TO BE 4188 02:53:06,218 --> 02:53:09,088 BY DR. MARK WALTERS FROM 4189 02:53:09,088 --> 02:53:09,722 UNIVERSITY OF CALIFORNIA SAN 4190 02:53:09,722 --> 02:53:14,226 FRANCISCO AND HE'S GOING TO BE 4191 02:53:14,226 --> 02:53:15,394 TALKING ABOUT CRISPR SICKLE CELL 4192 02:53:15,394 --> 02:53:17,763 DISEASE GENE EDITING TRYING 4193 02:53:17,763 --> 02:53:22,101 UPDATES. 4194 02:53:22,101 --> 02:53:22,334 MARK. 4195 02:53:22,334 --> 02:53:23,702 >> THANKS AND THANK YOU FOR THE 4196 02:53:23,702 --> 02:53:25,838 OPPORTUNITY TO GIVE THIS UPDATE. 4197 02:53:25,838 --> 02:53:31,443 SO HERE'S MY TITLE SLIDE. 4198 02:53:31,443 --> 02:53:34,613 I WANTED TO ALSO ACKNOWLEDGE THE 4199 02:53:34,613 --> 02:53:36,815 REMARKABLE PROJECT TEAM WE'VE 4200 02:53:36,815 --> 02:53:40,052 ASSEMBLED AT UNIVERSITY OF 4201 02:53:40,052 --> 02:53:40,552 CALIFORNIA CAMPUSES. 4202 02:53:40,552 --> 02:53:48,260 SO CURRENTLY IT'S LED BY THE 4203 02:53:48,260 --> 02:53:51,096 INNOVATIVE GENOMICS INSTITUTE AT 4204 02:53:51,096 --> 02:53:55,534 U.C. BERKELEY AND UCLA WITH THE 4205 02:53:55,534 --> 02:53:58,837 MANUFACTURING COMPONENT AND UCSF 4206 02:53:58,837 --> 02:54:04,710 AND HUMIDITY WORK OF THE IGI. 4207 02:54:04,710 --> 02:54:06,578 MORE IMPORTANT OF COURSE IS THE 4208 02:54:06,578 --> 02:54:08,781 FUNDING STREAM. 4209 02:54:08,781 --> 02:54:10,716 WE'VE BENEFITTED FROM A 4210 02:54:10,716 --> 02:54:12,251 COMBINATION OF CALIFORNIA 4211 02:54:12,251 --> 02:54:13,385 REGENERATIVE MEDICINE FUNDING 4212 02:54:13,385 --> 02:54:15,320 AND FOLLOWING A MEMORANDUM OF 4213 02:54:15,320 --> 02:54:20,392 UNDERSTANDING PARTNERSHIP WITH 4214 02:54:20,392 --> 02:54:21,693 CURE SICKLE CELL INITIATIVE. 4215 02:54:21,693 --> 02:54:23,128 THIS FUNDED PRECLINICAL 4216 02:54:23,128 --> 02:54:24,063 DEVELOPMENT OF THE PROJECT AND 4217 02:54:24,063 --> 02:54:28,133 NOW IN THE CLINICAL PHASE. 4218 02:54:28,133 --> 02:54:31,670 THIS IS A REMINDER OF THE 4219 02:54:31,670 --> 02:54:34,440 SCHEMATIC OF WHAT WE'RE 4220 02:54:34,440 --> 02:54:36,809 ATTEMPTING TO DO THE REPAIR AND 4221 02:54:36,809 --> 02:54:39,878 IN THE SCHEMATIC THERE'S THE 4222 02:54:39,878 --> 02:54:44,783 SEQUENCE OF THE SINGLE STRANDED 4223 02:54:44,783 --> 02:54:52,791 OLIGO NUCLEOTIDE DONOR AND GAA 4224 02:54:52,791 --> 02:54:56,428 TO HELP DISTINGUISH WILD TYPE 4225 02:54:56,428 --> 02:54:58,230 GLUCAMIC ACID DURING THE 4226 02:54:58,230 --> 02:54:59,431 PRECLINICAL DEVELOPMENT. 4227 02:54:59,431 --> 02:55:03,936 THE SITE IS EDITED AND THE 4228 02:55:03,936 --> 02:55:06,238 CLEAVAGE SITE IS SOMEWHAT 4229 02:55:06,238 --> 02:55:08,474 UPSTREAM OF THE CORRECTION SITE 4230 02:55:08,474 --> 02:55:10,509 SO HDR CAN OCCUR AND CORRECT THE 4231 02:55:10,509 --> 02:55:12,778 PAM BUT THE STRAPPED CAN FALL 4232 02:55:12,778 --> 02:55:19,384 OFF BEFORE IT REACHES THE ALLELE 4233 02:55:19,384 --> 02:55:20,719 AND THE COMPLEMENTARY GUIDE 4234 02:55:20,719 --> 02:55:23,122 SEQUENCES IS HIGHLIGHTED. 4235 02:55:23,122 --> 02:55:27,726 SO THESE WERE DATA I'VE SHOWN 4236 02:55:27,726 --> 02:55:30,596 BEFORE AND EACH GRAY DOT 4237 02:55:30,596 --> 02:55:36,235 RESPONSES A MOUSE IN IN VIVO 4238 02:55:36,235 --> 02:55:38,537 GENE EDITING PRE CLINICAL WORK 4239 02:55:38,537 --> 02:55:40,772 AND WE HAVE THE SECOND CONTROL 4240 02:55:40,772 --> 02:55:45,978 LEFT TO RIGHT OF THE ORANGE 4241 02:55:45,978 --> 02:55:47,946 COLORED ONE IS WHEN THERE'S PAM 4242 02:55:47,946 --> 02:55:54,253 ONLY HDR AND NO DIFFERENCE IN 4243 02:55:54,253 --> 02:56:01,260 EDITING ON UNFRACTIONATED 4244 02:56:01,260 --> 02:56:02,728 ERYTHROID LINEAGE AND YOU SEE 4245 02:56:02,728 --> 02:56:06,932 THE NICE ENRICHMENT FROM THE 20% 4246 02:56:06,932 --> 02:56:13,872 TO 25% OR SO MARROW NC34 4247 02:56:13,872 --> 02:56:15,507 POSITIVE POPULATION FOLLOWING 4248 02:56:15,507 --> 02:56:18,243 THE PRINCIPLES OF MIXED 4249 02:56:18,243 --> 02:56:22,781 CHIMERISM WITH IMPROVED SURVIVAL 4250 02:56:22,781 --> 02:56:24,716 OF THE CORRECTED ERYTHROID 4251 02:56:24,716 --> 02:56:26,752 PROGENITORS IN THE NICE TALK 4252 02:56:26,752 --> 02:56:32,324 GIVEN EARLIER BY ALEXUS LEONARD 4253 02:56:32,324 --> 02:56:37,196 AND NICE WORK BY GORDON FITZHUGH 4254 02:56:37,196 --> 02:56:41,133 SHOULD BE SUFFICIENT FOR A 4255 02:56:41,133 --> 02:56:44,503 CURATIVE AFFECT. 4256 02:56:44,503 --> 02:56:45,737 NON-HOMOLOGOUS EN JOINING IS OUT 4257 02:56:45,737 --> 02:56:49,408 OF FRAME ON THE FAR RIGHT PANEL 4258 02:56:49,408 --> 02:56:51,910 HAPPENS ABOUT 50% TO 70% OF THE 4259 02:56:51,910 --> 02:56:57,783 TIME. 4260 02:56:57,783 --> 02:56:59,618 UNFORTUNATELY IT CREATES THE 4261 02:56:59,618 --> 02:57:06,258 DROP OUT OF THE PROGENITORS AS 4262 02:57:06,258 --> 02:57:16,802 YOU PREDICT IN THE HALOCEMIA FOR 4263 02:57:20,005 --> 02:57:22,741 CLINICAL AFFECT. 4264 02:57:22,741 --> 02:57:28,780 SO WE SUCCESSFULLY COMPLETED OUR 4265 02:57:28,780 --> 02:57:30,015 PRE-CLINICAL MANUFACTURING 4266 02:57:30,015 --> 02:57:32,117 OUTCOMES USING CLINICAL GRADE 4267 02:57:32,117 --> 02:57:35,053 PATIENT MATERIALS IN THE 4268 02:57:35,053 --> 02:57:38,657 LABORATORY AND AGAIN CIRCLED ARE 4269 02:57:38,657 --> 02:57:40,759 THE HGR CORRECTION IN THE SIX 4270 02:57:40,759 --> 02:57:42,261 MONTHS WE RAN. 4271 02:57:42,261 --> 02:57:47,165 AND THE FIVE RUNS WE RAN WITH A 4272 02:57:47,165 --> 02:57:49,501 20% TO 25% CORRECTION BALANCED 4273 02:57:49,501 --> 02:57:52,404 BY A HIGHER FRACTION OF 4274 02:57:52,404 --> 02:57:56,375 INSERTION DELETION WITH A SINGLE 4275 02:57:56,375 --> 02:57:58,910 OFF-TARGET GENERALLY OCCURRING 4276 02:57:58,910 --> 02:58:08,453 5% OF THE TIME FULFILLED OUR INA 4277 02:58:08,453 --> 02:58:12,557 ENABLING GOALS FOR R&D. 4278 02:58:12,557 --> 02:58:15,661 WE HAVE SINCE COMPLETED THE 4279 02:58:15,661 --> 02:58:17,696 ACQUISITION OF CLINICAL GRADE 4280 02:58:17,696 --> 02:58:23,001 GMP GRADE RE-AGENTS AND SHOWS 4281 02:58:23,001 --> 02:58:25,437 THE COMPARABILITY TESTING ONE 4282 02:58:25,437 --> 02:58:28,974 MOST DIFFICULT TO CURE THE 4283 02:58:28,974 --> 02:58:29,741 SSOEN. 4284 02:58:29,741 --> 02:58:33,812 EACH BAR REPRESENTS A SICKLE 4285 02:58:33,812 --> 02:58:35,213 CELL DISEASE DONOR THE POSITIVE 4286 02:58:35,213 --> 02:58:37,983 CELLS FROM TWO DIFFERENT DONORS 4287 02:58:37,983 --> 02:58:41,787 AND COMPARES THE RNP ALONE WITH 4288 02:58:41,787 --> 02:58:45,290 OUR RESEARCH-USE ONLY TO GET 4289 02:58:45,290 --> 02:58:48,660 CLEARANCE OF THE IND AND THE 4290 02:58:48,660 --> 02:58:51,330 CURRENT CITY OF HOPE CLINICAL 4291 02:58:51,330 --> 02:58:51,830 GRADE. 4292 02:58:51,830 --> 02:58:57,736 YOU CAN SEE WITH VIABILITY AND 4293 02:58:57,736 --> 02:59:02,007 CLONOGENIC POTENTIAL THE OLICO 4294 02:59:02,007 --> 02:59:04,443 NUCLEOTIDES PERFORMED COMPARABLY 4295 02:59:04,443 --> 02:59:08,780 AND THE HDR AND NHEJ RATES ARE 4296 02:59:08,780 --> 02:59:09,881 ALSO COMPARABLE. 4297 02:59:09,881 --> 02:59:13,885 THIS CLEARED THE CLINICAL GRADE 4298 02:59:13,885 --> 02:59:15,787 SSODN FOR CLINICAL 4299 02:59:15,787 --> 02:59:16,288 MANUFACTURING. 4300 02:59:16,288 --> 02:59:19,791 FINALLY WE RECENTLY COMPLETED A 4301 02:59:19,791 --> 02:59:21,993 CLINICAL SCALE RUN USING ALL GNP 4302 02:59:21,993 --> 02:59:28,133 GRADE RE-AGENTS IN THE GENE 4303 02:59:28,133 --> 02:59:34,373 EDITING LABORATORY AT UCLA AND 4304 02:59:34,373 --> 02:59:37,376 WE AND DON COMBS' TEAMS HANDS 4305 02:59:37,376 --> 02:59:40,779 HAD RELEASE IN GENE EDITING AND 4306 02:59:40,779 --> 02:59:42,114 FREQUENCY AND OFF-TARGET 4307 02:59:42,114 --> 02:59:46,818 EDITING. 4308 02:59:46,818 --> 02:59:49,554 JUST TO GO THROUGH THE TIME 4309 02:59:49,554 --> 02:59:49,788 LINE. 4310 02:59:49,788 --> 02:59:55,927 THE IND WAS OBTAINED IN 2020 AND 4311 02:59:55,927 --> 02:59:58,063 THE PANDEMIC OCCURRED AND GOT 4312 02:59:58,063 --> 03:00:01,166 FUNDING RELEASED IN LATE 2021 4313 03:00:01,166 --> 03:00:03,034 AND JUST COMPLETED OUR 4314 03:00:03,034 --> 03:00:07,205 INITIATION VISIT AT UCLA AND 4315 03:00:07,205 --> 03:00:09,307 UCSF AND ANTICIPATE THE FIRST 4316 03:00:09,307 --> 03:00:10,909 PATIENT WILL BE ENROLLED NEXT 4317 03:00:10,909 --> 03:00:11,309 MONTH. 4318 03:00:11,309 --> 03:00:16,081 THIS WILL TAKE SEVERAL YEARS TO 4319 03:00:16,081 --> 03:00:19,951 COMPLETE THE UP TO NINE PATIENT 4320 03:00:19,951 --> 03:00:20,519 TRIAL. 4321 03:00:20,519 --> 03:00:22,654 SO THIS IS IN GREEN THIS TIME 4322 03:00:22,654 --> 03:00:22,921 LINE. 4323 03:00:22,921 --> 03:00:24,523 THIS WAS PRE-PANDEMIC. 4324 03:00:24,523 --> 03:00:26,825 IT WAS VERY OPTIMISTIC. 4325 03:00:26,825 --> 03:00:29,795 WE THOUGHT WE'D GET CLEARED OF 4326 03:00:29,795 --> 03:00:32,764 OUR FDA IND BY THE FALL OF 2020 4327 03:00:32,764 --> 03:00:35,734 AND WOULD APPLY FOR CLINICAL 4328 03:00:35,734 --> 03:00:38,370 TRIAL FUNDING IMMEDIATELY AND 4329 03:00:38,370 --> 03:00:40,172 WOULD HAVE IT IN HAND 2021 AND 4330 03:00:40,172 --> 03:00:44,776 BEGIN TO ENROLL PATIENTS. 4331 03:00:44,776 --> 03:00:47,245 THE NEXT SLIDE IS NOT GREEN IT'S 4332 03:00:47,245 --> 03:00:49,347 A REDDISH HUE AND JUST 4333 03:00:49,347 --> 03:00:50,382 ILLUSTRATES SOME OF THE 4334 03:00:50,382 --> 03:00:52,250 CHALLENGES WE EXPERIENCED ON OUR 4335 03:00:52,250 --> 03:00:54,085 WAY TO CLINICAL READINESS TO 4336 03:00:54,085 --> 03:00:57,989 COMMENCE PATIENT ENROLLMENT. 4337 03:00:57,989 --> 03:01:01,693 SO IT DID TAKE SEVERAL TWO 4338 03:01:01,693 --> 03:01:03,562 ROUNDS OF GRANT SUBMISSION AND 4339 03:01:03,562 --> 03:01:07,532 ULTIMATELY WE WERE SUCCESSFUL IN 4340 03:01:07,532 --> 03:01:10,469 PROCURING FUNDS BY THE END OF 4341 03:01:10,469 --> 03:01:10,669 2021. 4342 03:01:10,669 --> 03:01:12,671 WE ENGAGED A MANUFACTURING 4343 03:01:12,671 --> 03:01:14,573 FACILITY TO MAKE THE CLINICAL 4344 03:01:14,573 --> 03:01:18,510 GRADE SSODN IN 2021 AND EXPECTED 4345 03:01:18,510 --> 03:01:21,746 TO HAVE IT IN ONE YEAR TIME FOR 4346 03:01:21,746 --> 03:01:24,850 OCTOBER '22. 4347 03:01:24,850 --> 03:01:27,719 UNFORTUNATELY, THERE WERE 4348 03:01:27,719 --> 03:01:29,154 SIGNIFICANT DELAYS DUE TO 4349 03:01:29,154 --> 03:01:30,288 MANUFACTURING MATERIAL SUPPLY 4350 03:01:30,288 --> 03:01:33,191 CHAIN PROBLEMS THAT WERE VERY 4351 03:01:33,191 --> 03:01:35,460 COMMON IN THE PANDEMIC AND ITS 4352 03:01:35,460 --> 03:01:38,463 RECOVERY, AS YOU MIGHT REMEMBER 4353 03:01:38,463 --> 03:01:41,600 AND KEPT PLUGGING LONG AND HAD 4354 03:01:41,600 --> 03:01:43,134 AMENDMENTS ADDED TO THE IND AND 4355 03:01:43,134 --> 03:01:49,574 A CLINICAL PROTOCOL WAS IN 2022. 4356 03:01:49,574 --> 03:01:52,444 THIS GETS BRIGHT RED BECAUSE WE 4357 03:01:52,444 --> 03:01:55,146 HAD ONGOING DELAYS WITH THE 4358 03:01:55,146 --> 03:01:56,948 SSODN READINESS DELAY AND FILM 4359 03:01:56,948 --> 03:02:00,285 FINISH ULTIMATELY THE SSODN WAS 4360 03:02:00,285 --> 03:02:03,488 RELEASED IN JANUARY 2024. 4361 03:02:03,488 --> 03:02:05,757 DURING THIS PERIOD WE ALSO 4362 03:02:05,757 --> 03:02:07,659 DISCOVERED SINGLE NUCLEOTIDE 4363 03:02:07,659 --> 03:02:10,395 ERRORS IN THE SSODN THAT 4364 03:02:10,395 --> 03:02:12,197 RESULTED IN OUR FILING AN 4365 03:02:12,197 --> 03:02:14,466 AMENDMENT IN OCTOBER 2023 WITH A 4366 03:02:14,466 --> 03:02:16,334 MITIGATION PLAN ACCEPTED BY THE 4367 03:02:16,334 --> 03:02:24,042 FDA AND THEN SET UP OUR CLINICAL 4368 03:02:24,042 --> 03:02:26,511 GENOMIC SEQUENCING AND PROCESSES 4369 03:02:26,511 --> 03:02:28,914 LOCALLY AT UCSF. 4370 03:02:28,914 --> 03:02:32,350 I'M HAPPY TO SAY WE COMPLETED 4371 03:02:32,350 --> 03:02:33,652 THE INITIATION VISIT AT BOTH 4372 03:02:33,652 --> 03:02:36,321 CENTERS AND SHOULD BEGIN 4373 03:02:36,321 --> 03:02:37,055 ENROLLMENT NEXT MONTH. 4374 03:02:37,055 --> 03:02:38,590 BUT IT WAS A DAUNTING EXPERIENCE 4375 03:02:38,590 --> 03:02:40,125 FROM THE START AS WE STARTED TO 4376 03:02:40,125 --> 03:02:42,160 DO THE PRE-CLINICAL TESTING 4377 03:02:42,160 --> 03:02:46,197 OPTIMIZING THE EDITORS IN 2015 4378 03:02:46,197 --> 03:02:47,065 AND HERE WE ARE NINE AND A HALF 4379 03:02:47,065 --> 03:02:52,737 YEARS LATER TO ILLUSTRATE THE 4380 03:02:52,737 --> 03:02:58,843 PACE THINGS CAN SOMETIMES GO. 4381 03:02:58,843 --> 03:03:04,749 THIS IS DATA LAST YEAR WHEN WE 4382 03:03:04,749 --> 03:03:08,620 DISCOVERED SINGLE NUCLEOTIDE 4383 03:03:08,620 --> 03:03:13,625 ERRORS WITHIN THE SITE WITH THE 4384 03:03:13,625 --> 03:03:14,092 RESEARCH GREAT OLIGO. 4385 03:03:14,092 --> 03:03:16,561 THE CLINICAL GRADE ERROR RATE IS 4386 03:03:16,561 --> 03:03:18,563 MUCH LOWER GENERALLY LESS THAN 4387 03:03:18,563 --> 03:03:19,764 2% COMPARING THE GREEN SPIKES 4388 03:03:19,764 --> 03:03:23,401 FROM THE RESEARCH USE ONLY TO 4389 03:03:23,401 --> 03:03:24,903 THE ORANGE AND BLUE SPIKES WITH 4390 03:03:24,903 --> 03:03:26,271 THE CLINICAL GRADE. 4391 03:03:26,271 --> 03:03:30,875 SO THAT'S VERY GOOD NEWS. 4392 03:03:30,875 --> 03:03:32,310 OF INTEREST THE AREAS APPEAR TO 4393 03:03:32,310 --> 03:03:35,146 BE OCCURRING AT THE SAME BASIS 4394 03:03:35,146 --> 03:03:36,014 IN THE SYNTHESIS PATTERN. 4395 03:03:36,014 --> 03:03:41,686 SO WHY THIS HAPPENS IS A MYSTERY 4396 03:03:41,686 --> 03:03:46,858 AND IS SOMETHING THAT WILL 4397 03:03:46,858 --> 03:03:50,495 CONTINUE TO CHALLENGE THE 4398 03:03:50,495 --> 03:03:56,434 SYNTHESIS OLIGO NUCLEOTIDES FOR 4399 03:03:56,434 --> 03:03:56,835 HDR. 4400 03:03:56,835 --> 03:04:01,239 THE MOST COMMON SNIPS INTRODUCED 4401 03:04:01,239 --> 03:04:03,174 DO CREATE VARIANT HEMOGLOBINS 4402 03:04:03,174 --> 03:04:06,344 BUT I WAS HAPPY TO SHOW LAST 4403 03:04:06,344 --> 03:04:08,546 YEAR THESE ARE FOR THE MOST PART 4404 03:04:08,546 --> 03:04:14,419 COMPLETELY BENIGN AND PRO 4405 03:04:14,419 --> 03:04:14,853 SICKLING VARIANTS. 4406 03:04:14,853 --> 03:04:16,621 IT PROVIDES AN OPPORTUNITY FOR 4407 03:04:16,621 --> 03:04:23,128 BAR CODING, IF YOU WILL, TO LOOK 4408 03:04:23,128 --> 03:04:24,629 AT COLONIES AND CLONES GENERATED 4409 03:04:24,629 --> 03:04:26,031 THROUGH THE MANUFACTURING 4410 03:04:26,031 --> 03:04:31,202 PROCESS THAT WE'LL COME BACK TO. 4411 03:04:31,202 --> 03:04:34,005 SO, WHEN THIS WAS PUBLISHED 4412 03:04:34,005 --> 03:04:36,808 EARLIER THIS YEAR FROM CINDY 4413 03:04:36,808 --> 03:04:37,809 DUMBAR'S GROUP IT RAISED 4414 03:04:37,809 --> 03:04:43,114 CONCERNS IN ADDITION TO THE 4415 03:04:43,114 --> 03:04:47,052 SINGLE ENROLLMENT BIO WHERE 4416 03:04:47,052 --> 03:04:52,357 PERHAPS A LIMITING NUMBER OF 4417 03:04:52,357 --> 03:04:54,259 STEM CELLS WERE COMMON IN BOTH 4418 03:04:54,259 --> 03:04:56,795 THE CLINICAL SETTING AND IN THE 4419 03:04:56,795 --> 03:04:58,830 RHESUS MACAQUE MODEL. 4420 03:04:58,830 --> 03:05:01,933 WHAT CINDY'S GROUP SHOWED IS 4421 03:05:01,933 --> 03:05:05,503 TARGETING CD33 THEY WERE ABLE TO 4422 03:05:05,503 --> 03:05:11,242 GET IN PANEL B ABOUT 15% TO 20% 4423 03:05:11,242 --> 03:05:13,244 IN THE DRUG PRODUCT GENERATED 4424 03:05:13,244 --> 03:05:17,949 FROM THESE NON-HUMAN PRIMATES 4425 03:05:17,949 --> 03:05:19,451 AND IN THE PRODUCT IN THE VERY 4426 03:05:19,451 --> 03:05:24,089 DARK COLORS ARE THE THREE 4427 03:05:24,089 --> 03:05:27,525 DIFFERENT HGR ALLELE ASSORTMENT 4428 03:05:27,525 --> 03:05:29,928 AF THE EDITING TO ACCOUNT FOR 4429 03:05:29,928 --> 03:05:32,464 15% TO 20%. 4430 03:05:32,464 --> 03:05:33,998 BY SIX MONTHS POST TRANSPLANT IN 4431 03:05:33,998 --> 03:05:38,136 THE MODEL ALMOST ALL THE CD33 4432 03:05:38,136 --> 03:05:42,407 WAS WILD TYPE WITHOUT 4433 03:05:42,407 --> 03:05:48,980 PERSISTENCE OF HGR HEMATOPOIETIC 4434 03:05:48,980 --> 03:05:56,788 STEM CELLS COMPARED WITH THE 4435 03:05:56,788 --> 03:06:01,092 LENITY VECTOR COMPARED TO 4436 03:06:01,092 --> 03:06:03,428 INDELS IN GRAY AND HGR IN BRIGHT 4437 03:06:03,428 --> 03:06:05,630 ORANGE AND THE HGR ACCOUNTS FOR 4438 03:06:05,630 --> 03:06:07,665 FAR LESS THAN 1% OF THE 4439 03:06:07,665 --> 03:06:09,968 LONG-TERM REPOPULATING CELLS. 4440 03:06:09,968 --> 03:06:11,870 SO THESE TWO EXPERIENCES GAVE US 4441 03:06:11,870 --> 03:06:14,239 GREAT PAUSE AND OF COURSE WE'RE 4442 03:06:14,239 --> 03:06:16,107 VERY CONCERNED ABOUT RELIABILITY 4443 03:06:16,107 --> 03:06:19,077 OF OUR MOUSE MODEL COMPARED TO 4444 03:06:19,077 --> 03:06:24,349 THE CLINICAL AND NON-HUMAN 4445 03:06:24,349 --> 03:06:26,518 PRIMATE EXPERIENCE AND GET TO 4446 03:06:26,518 --> 03:06:31,122 REPOPULATED STEM CELLS TO HAVE A 4447 03:06:31,122 --> 03:06:34,125 CLINICAL BENEFIT. 4448 03:06:34,125 --> 03:06:36,094 IN OUR 2016 ITERATION OF THE 4449 03:06:36,094 --> 03:06:38,329 MANUFACTURING PROTOCOLS WE SAW 4450 03:06:38,329 --> 03:06:41,399 SOMETHING SIMILAR IF YOU LOOK AT 4451 03:06:41,399 --> 03:06:49,340 PANEL B, 10% TO 15% HGR IN BLUE 4452 03:06:49,340 --> 03:06:52,944 AND IN WEEK 16, 2% TO 3% EDITING 4453 03:06:52,944 --> 03:06:55,013 IN THE REPOPULATING STEM CELLS. 4454 03:06:55,013 --> 03:06:59,217 SO A SIGNIFICANT DROP OUT AS 4455 03:06:59,217 --> 03:07:00,952 CINDY DUMBAR SHOWED IN THE 4456 03:07:00,952 --> 03:07:03,988 NON-HUMAN PRIMATES AND WITH 4457 03:07:03,988 --> 03:07:05,690 IMPROVEMENTS AND THE PANEL 4458 03:07:05,690 --> 03:07:06,758 PUBLISHED YEARS AGO EACH OPEN 4459 03:07:06,758 --> 03:07:12,030 CIRCLE FOR THE COHORT OF MICE 4460 03:07:12,030 --> 03:07:15,700 DEPICTED IS THE INPUT 4461 03:07:15,700 --> 03:07:16,367 INVESTIGATIONAL PRODUCT COMPARED 4462 03:07:16,367 --> 03:07:21,039 TO ON THE MIDDLE PANEL B THE HGR 4463 03:07:21,039 --> 03:07:23,641 RATE AT THE MICE IN 16 TO 18 4464 03:07:23,641 --> 03:07:23,842 WEEKS. 4465 03:07:23,842 --> 03:07:26,010 WHILE THERE'S SOME DROP OFF IN 4466 03:07:26,010 --> 03:07:31,683 COHORT 1 AND 3, COHORTS 2 AND 3 4467 03:07:31,683 --> 03:07:33,384 SHOWED LITTLE DROP OFF IN 4468 03:07:33,384 --> 03:07:35,820 GENERAL AND THE BOTTOM PANEL 4469 03:07:35,820 --> 03:07:38,923 SHOWED NON-HOMOLOGOUS END 4470 03:07:38,923 --> 03:07:39,424 JOINING. 4471 03:07:39,424 --> 03:07:41,025 SOME ENRICHMENT BUT NOT 4472 03:07:41,025 --> 03:07:43,661 SIGNIFICANT AND WE ARGUE THE 4473 03:07:43,661 --> 03:07:45,930 IMPROVEMENTS INSTITUTED IN OUR 4474 03:07:45,930 --> 03:07:46,865 MANUFACTURING PROTOCOL MADE STEM 4475 03:07:46,865 --> 03:07:52,237 CELL EDITING VIA HGR AN EVENT 4476 03:07:52,237 --> 03:07:52,770 THAT OCCURS. 4477 03:07:52,770 --> 03:07:58,743 IN FACT THIS IS ILLUSTRATED 4478 03:07:58,743 --> 03:08:00,111 NICELY IN THE LABORATORY 4479 03:08:00,111 --> 03:08:02,680 COMPARING DIFFERENT MEDIA 4480 03:08:02,680 --> 03:08:02,981 CONDITIONS. 4481 03:08:02,981 --> 03:08:07,585 THE AOF AT THE TOP IS THE GMP 4482 03:08:07,585 --> 03:08:10,521 GRADE MEDIA WE USE CURRENTLY IN 4483 03:08:10,521 --> 03:08:11,456 THE LAB. 4484 03:08:11,456 --> 03:08:14,225 AND EX VIVO 15 FOR YEARS HAS 4485 03:08:14,225 --> 03:08:19,497 BEEN THE STANDARD MEDIA USE FOR 4486 03:08:19,497 --> 03:08:21,966 LET'S SAY LENITY VIRAL GENE 4487 03:08:21,966 --> 03:08:22,567 THERAPY MANUFACTURING. 4488 03:08:22,567 --> 03:08:29,707 WHAT THE AOF DID AND THE SFEM 4489 03:08:29,707 --> 03:08:33,511 DID MOVE MORE CELLS TO G1 WHERE 4490 03:08:33,511 --> 03:08:37,348 HGR CAN OCCUR AND ON THE BOTTOM 4491 03:08:37,348 --> 03:08:40,818 LEFT THE RATIO IMPROVED WHEN AOF 4492 03:08:40,818 --> 03:08:42,787 WAS IMPROVED AND THIS 4493 03:08:42,787 --> 03:08:44,188 ILLUSTRATES ONE OF THE THINGS 4494 03:08:44,188 --> 03:08:53,698 WE'VE DONE TO SELECT FOR HGR. 4495 03:08:53,698 --> 03:08:55,700 SO, THIS JUST SHOWED USING THE 4496 03:08:55,700 --> 03:09:00,405 BAR CODING THAT IN COHORT 1 MICE 4497 03:09:00,405 --> 03:09:03,608 YOU SEE THIS POLY CLONAL 4498 03:09:03,608 --> 03:09:04,909 DISTRIBUTION AT 18 WEEKS. 4499 03:09:04,909 --> 03:09:07,345 SO WE THINK WE'RE GETTING HGR 4500 03:09:07,345 --> 03:09:09,113 OCCURRING IN THE STEM CELLS IS 4501 03:09:09,113 --> 03:09:12,050 POLY CLONAL USING THE BAR CODING 4502 03:09:12,050 --> 03:09:13,985 WE HAVE AVAILABLE NOW AND GIVES 4503 03:09:13,985 --> 03:09:15,386 US HOPE AND CONFIDENCE TO 4504 03:09:15,386 --> 03:09:17,088 CONDUCT THE CLINICAL TRIAL. 4505 03:09:17,088 --> 03:09:19,624 SO THE LAST SLIGHT JUST 4506 03:09:19,624 --> 03:09:21,125 SUMMARIZES WHAT I PRESENTED. 4507 03:09:21,125 --> 03:09:23,027 THE CRITICAL QUESTIONS WILL THE 4508 03:09:23,027 --> 03:09:27,365 BALANCE OF ON TARGET INSERTION 4509 03:09:27,365 --> 03:09:33,638 DELETIONS AND HOMOLOGOUS REPAIR 4510 03:09:33,638 --> 03:09:39,410 BE BENEFICIAL FOR THE TYPE AND 4511 03:09:39,410 --> 03:09:41,980 IS THERE RISK OCCUR AND THE COST 4512 03:09:41,980 --> 03:09:47,552 RESTRICT ACCESS TO CARE. 4513 03:09:47,552 --> 03:09:57,095 THESE ARE ALL AND THANK YOU FOR 4514 03:09:57,095 --> 03:10:02,333 YOUR ATTENTION. 4515 03:10:02,333 --> 03:10:04,035 >> THANK YOU, MARK. 4516 03:10:04,035 --> 03:10:05,536 WE'LL MOVE TO OUR NEXT TALK 4517 03:10:05,536 --> 03:10:10,208 WHICH IS UPDATE ON THE BCL11A 4518 03:10:10,208 --> 03:10:15,913 LENTIVIRUS TRIAL AND DR. DAVID 4519 03:10:15,913 --> 03:10:18,516 WILLIAMS FROM HARVARD BOSTON'S 4520 03:10:18,516 --> 03:10:19,217 CHILDREN'S HOSPITAL. 4521 03:10:19,217 --> 03:10:25,423 >> I'M IN CLINIC BUT I HOPE TO 4522 03:10:25,423 --> 03:10:27,592 GO IN TOMORROW MORNING ALLOWING. 4523 03:10:27,592 --> 03:10:33,865 I WANTED TO START BY LIKE MARK 4524 03:10:33,865 --> 03:10:35,366 THANKING THE BLOOD DIVISION OF 4525 03:10:35,366 --> 03:10:36,801 NHLBI FOR SUPPORTING OUR TWO 4526 03:10:36,801 --> 03:10:45,309 TRIALS I'LL TALK ABOUT TODAY. 4527 03:10:45,309 --> 03:10:48,012 AND THE SUPPORT OF THE GRAFT 4528 03:10:48,012 --> 03:10:50,715 TRIAL AND THE LARGE GROUP AT 4529 03:10:50,715 --> 03:10:55,920 NHLBI THAT'S BEEN HELPFUL TO US 4530 03:10:55,920 --> 03:10:58,122 AND CALL OUT SUPPORT OF WHAT 4531 03:10:58,122 --> 03:11:03,728 WE'RE TRYING TO DO. 4532 03:11:03,728 --> 03:11:05,530 SO I WON'T BELABOR THIS IT'S 4533 03:11:05,530 --> 03:11:06,864 BEEN TALKED ABOUT AND DAN BAUER 4534 03:11:06,864 --> 03:11:09,300 DID A GREAT JOB THIS MORNING AND 4535 03:11:09,300 --> 03:11:11,002 THE GROUP KNOWS THIS ALREADY I 4536 03:11:11,002 --> 03:11:14,605 THINK BUT THERE'S A REASON TO 4537 03:11:14,605 --> 03:11:15,339 FOCUS ON FETAL HEMOGLOBIN 4538 03:11:15,339 --> 03:11:16,774 INDUCTION IN THE DISEASE AND 4539 03:11:16,774 --> 03:11:25,516 LOTS OF STUDIES IN THE PAST HAVE 4540 03:11:25,516 --> 03:11:30,855 SHOWN THAT EARLY IN NEWBORN LIFE 4541 03:11:30,855 --> 03:11:33,324 AND THE FETAL HEMOGLOBIN IS HIGH 4542 03:11:33,324 --> 03:11:37,128 THERE'S NO SYMPTOMS OF SICKLE 4543 03:11:37,128 --> 03:11:38,529 CELL AND SYMPTOMS OCCUR WHEN THE 4544 03:11:38,529 --> 03:11:40,098 BETA CELL IS TURNED ON. 4545 03:11:40,098 --> 03:11:43,401 THIS HAS BEEN DOCUMENTED NOW 4546 03:11:43,401 --> 03:11:44,769 THROUGH MANY YEARS WITH CLINICAL 4547 03:11:44,769 --> 03:11:51,509 DATA. 4548 03:11:51,509 --> 03:11:58,983 STUDIES SHOW PAIN AND FREQUENCY 4549 03:11:58,983 --> 03:12:04,388 AND EVEN DURATION OF LIFE ARE 4550 03:12:04,388 --> 03:12:05,223 ATTENUATED BY HIGHER HEMOGLOBIN 4551 03:12:05,223 --> 03:12:07,758 AND I'LL POINT OUT FROM A PAPER 4552 03:12:07,758 --> 03:12:11,896 A LONG TIME AGO HERE WE'RE 4553 03:12:11,896 --> 03:12:12,530 TALKING ABOUT FETAL HEMOGLOBIN 4554 03:12:12,530 --> 03:12:18,269 LEVELS ABOVE AND BELOW THE 9%. 4555 03:12:18,269 --> 03:12:19,604 WE'LL COME BACK TO THAT IN A 4556 03:12:19,604 --> 03:12:19,871 MINUTE. 4557 03:12:19,871 --> 03:12:27,044 AS YOU PROBABLY KNOW, GWAS 4558 03:12:27,044 --> 03:12:34,318 STUDIES IMPLICATED THE GENE 11A 4559 03:12:34,318 --> 03:12:37,188 AS A REGULATOR OF HEMOGLOBIN AND 4560 03:12:37,188 --> 03:12:39,657 IT'S A B CELL TRANSCRIPTION 4561 03:12:39,657 --> 03:12:42,426 FACTOR AND STUDIES WENT ON TO 4562 03:12:42,426 --> 03:12:44,228 VALIDATE THIS IN MODELS OF 4563 03:12:44,228 --> 03:12:46,130 SICKLE CELL DISEASE. 4564 03:12:46,130 --> 03:12:50,668 SO AS DAN POINTED OUT ALREADY, 4565 03:12:50,668 --> 03:12:54,405 OUR APPROACH IS TO USE LENITY 4566 03:12:54,405 --> 03:13:00,411 VIRAL VECTORS TO SWITCH FROM 4567 03:13:00,411 --> 03:13:02,413 BETA GLOBIN BACK TO FETAL AND 4568 03:13:02,413 --> 03:13:07,852 THAT'S OUR GOAL AND INCREASING 4569 03:13:07,852 --> 03:13:09,387 THE AFFECT OF HEMOGLOBIN F WHILE 4570 03:13:09,387 --> 03:13:12,323 REDUCING THE CONCENTRATION IN 4571 03:13:12,323 --> 03:13:16,294 THE CELL SIMULTANEOUSLY AND 4572 03:13:16,294 --> 03:13:16,627 COORDINATEDLY. 4573 03:13:16,627 --> 03:13:20,364 SO BASICALLY WE'RE TREATING 4574 03:13:20,364 --> 03:13:25,169 BCL11 AS A BINARY SWITCH INDUCE 4575 03:13:25,169 --> 03:13:25,636 LARGE LEVELS OF FETAL 4576 03:13:25,636 --> 03:13:28,139 HEMOGLOBIN. 4577 03:13:28,139 --> 03:13:36,914 TO DO THIS WE GENERATED A LENTI 4578 03:13:36,914 --> 03:13:37,481 VIRAL VECTOR THAT KNOCKS DOWN 4579 03:13:42,486 --> 03:13:46,691 BCL11A AND CALL THIS A SHARER. 4580 03:13:46,691 --> 03:13:48,426 THE REASON IS TWO. 4581 03:13:48,426 --> 03:13:55,066 IT ALLOWS US TO EXPRESS THE 4582 03:13:55,066 --> 03:13:57,535 SHRNA AT LEVEL CONSISTENT WITH 4583 03:13:57,535 --> 03:14:01,572 MICRORNA AND SECOND ALLOWS US TO 4584 03:14:01,572 --> 03:14:06,477 EXPRESS ONLY IN THE ERYTHROID 4585 03:14:06,477 --> 03:14:08,212 AND BY USING MICRORNA BACKBONE 4586 03:14:08,212 --> 03:14:11,482 WE CAN USE THE PROMOTER AND HS2 4587 03:14:11,482 --> 03:14:15,853 AND HS3 WITH THE MINIMAL BETA 4588 03:14:15,853 --> 03:14:17,054 PROMOTER AND IT WENT QUITE WELL. 4589 03:14:17,054 --> 03:14:19,657 THIS LED TO OUR FIRST STUDY 4590 03:14:19,657 --> 03:14:23,127 WHICH WAS A FEASIBILITY STUDY AT 4591 03:14:23,127 --> 03:14:25,129 THE SINGLE SITE STUDY INITIALLY 4592 03:14:25,129 --> 03:14:27,698 SEVEN PATIENTS TO BE ENROLLED 4593 03:14:27,698 --> 03:14:29,033 AND WE DID 10 BECAUSE THE TRIAL 4594 03:14:29,033 --> 03:14:33,971 WENT SO WELL. 4595 03:14:33,971 --> 03:14:35,339 WE HAD THREE DIFFERENT AGE 4596 03:14:35,339 --> 03:14:36,807 GROUPS AND AMENDED THIS AFTER 4597 03:14:36,807 --> 03:14:40,244 THE STUDY WAS STARTED THE LOWER 4598 03:14:40,244 --> 03:14:43,581 AGE GROUP TO INCREASE IT TO H12 4599 03:14:43,581 --> 03:14:47,952 BASED ON DATA FROM MARY'S PAPER 4600 03:14:47,952 --> 03:14:49,954 ON OUTCOMES OF IMPLANTATION. 4601 03:14:49,954 --> 03:14:52,590 YOU COULD NOT HAVE A MATCH 4602 03:14:52,590 --> 03:14:56,427 SIBLING DONOR AND COULD HAVE A 4603 03:14:56,427 --> 03:15:03,100 PHENOTYPE THAT FAILED HYDROXY 4604 03:15:03,100 --> 03:15:05,603 UREA AND THE BMP VECTOR WAS 4605 03:15:05,603 --> 03:15:12,443 PRODUCED AS PART OF A LICENSE 4606 03:15:12,443 --> 03:15:16,781 AGREEM 4607 03:15:16,781 --> 03:15:22,153 AGREEMENT. 4608 03:15:22,153 --> 03:15:25,756 THIS IS THE LENTI VIRAL PROTOCOL 4609 03:15:25,756 --> 03:15:26,424 AND MOBILIZED STEM CELLS I'LL 4610 03:15:26,424 --> 03:15:30,528 COME BACK TO IN A MOMENT. 4611 03:15:30,528 --> 03:15:33,631 AND THE BLOOD WAS TRANSDUCED AND 4612 03:15:33,631 --> 03:15:36,467 AFTER CRITERIA WAS MET THE 4613 03:15:36,467 --> 03:15:40,571 PATIENT WAS ADMITTED. 4614 03:15:40,571 --> 03:15:43,240 SO OUR INITIAL DATA WERE 4615 03:15:43,240 --> 03:15:45,843 PUBLISHED IN 2021 IN JANUARY AND 4616 03:15:45,843 --> 03:15:50,081 WE CALL THIS APPROACH 4617 03:15:50,081 --> 03:15:51,482 POST-TRANSCRIPTIONAL GENETIC 4618 03:15:51,482 --> 03:15:52,883 SILENCING OPPOSED TO GENE 4619 03:15:52,883 --> 03:15:54,452 EDITING BECAUSE WE ARE NOT DOING 4620 03:15:54,452 --> 03:15:57,722 DOUBLE STRAND BREAK TO ADD IT AT 4621 03:15:57,722 --> 03:16:08,265 THE BCL11A LOCUS AND FIRST PROOF 4622 03:16:09,934 --> 03:16:11,068 AS A TARGET. 4623 03:16:11,068 --> 03:16:14,338 I WANT TO TALK A MINUTE ABOUT 4624 03:16:14,338 --> 03:16:16,607 THE ADDITIONAL SAFETY THAT CAME 4625 03:16:16,607 --> 03:16:20,010 UP THIS MORNING SEVERAL TIMES. 4626 03:16:20,010 --> 03:16:24,682 THIS WAS THE FIRST TIME A 4627 03:16:24,682 --> 03:16:28,519 CHIMERIC THERAPY WAS USED AND AS 4628 03:16:28,519 --> 03:16:32,289 SPOKE ABOUT THIS MORNING IN THE 4629 03:16:32,289 --> 03:16:34,525 VIRAL IT'S A DIFFERENT 4630 03:16:34,525 --> 03:16:37,328 LENTIVIRAL VECTOR DESIGN AND 4631 03:16:37,328 --> 03:16:38,662 REQUIRED US TO IMPLEMENT 4632 03:16:38,662 --> 03:16:42,867 ANALYSIS FOR MUTATION ASSOCIATED 4633 03:16:42,867 --> 03:16:45,536 AS PART OF THE PILOT STUDY. 4634 03:16:45,536 --> 03:16:48,472 WE USED WHAT'S CALLED THE RAPID 4635 03:16:48,472 --> 03:16:51,075 HEME PANEL AT BRIGHAM AND 4636 03:16:51,075 --> 03:16:52,543 WOMEN'S HOSPITAL TO THE 4637 03:16:52,543 --> 03:16:55,679 CERTIFIED PANEL AND WE PUBLISHED 4638 03:16:55,679 --> 03:16:58,682 ANALYSIS POST-ENROLLMENT AND 4639 03:16:58,682 --> 03:17:00,117 POST TREATMENT A NUMBER OF 4640 03:17:00,117 --> 03:17:02,720 PATIENTS USING BANK STUDIES AND 4641 03:17:02,720 --> 03:17:04,688 PROSPECTIVELY FROM THAT POINT ON 4642 03:17:04,688 --> 03:17:08,859 AND I'LL TOUCH ON THE DATA IN A 4643 03:17:08,859 --> 03:17:09,093 MINUTE. 4644 03:17:09,093 --> 03:17:12,463 SO TODAY OVER 50 SAMPLE HAVE 4645 03:17:12,463 --> 03:17:16,767 BEEN ANALYZED USING THE TEST 4646 03:17:16,767 --> 03:17:19,637 WITH LONGEST FOLLOW-UP A LITTLE 4647 03:17:19,637 --> 03:17:23,641 OVER FOUR YEARS AND SHORTEST LAT 4648 03:17:23,641 --> 03:17:25,309 OVER THREE YEARS AND DID 4649 03:17:25,309 --> 03:17:27,311 ANALYSIS ON THE PATIENTS AND 4650 03:17:27,311 --> 03:17:27,945 I'LL TOUCH ON THE SAFETY DATA 4651 03:17:27,945 --> 03:17:30,448 ALSO. 4652 03:17:30,448 --> 03:17:32,750 SO I DID WANT TO MAKE THIS POINT 4653 03:17:32,750 --> 03:17:38,522 WHICH HAS NOT BEEN TALKED ABOUT 4654 03:17:38,522 --> 03:17:40,191 VERY MUCH TODAY. 4655 03:17:40,191 --> 03:17:44,161 BUT USING JOHN NAS' EXPERTISE WE 4656 03:17:44,161 --> 03:17:44,795 WERE ABLE TO MANUFACTURE 4657 03:17:44,795 --> 03:17:46,430 OUTSTANDING PRODUCTS FOR THE 4658 03:17:46,430 --> 03:17:48,432 PATIENTS AND FOR ALL BUT ONE OF 4659 03:17:48,432 --> 03:17:52,036 THEM THAT OCCURRED IN JUST ONE 4660 03:17:52,036 --> 03:17:54,205 MOBILIZATION COLLECTION CYCLE. 4661 03:17:54,205 --> 03:17:57,208 ONE PATIENT REQUIRED TWO AND IN 4662 03:17:57,208 --> 03:18:06,450 THESE THERE WERE TWO EFOREESE 4663 03:18:09,086 --> 03:18:16,760 AND I'LL CALL OUT THIS IS MY 4664 03:18:16,760 --> 03:18:20,764 COLLEAGUE AND THIS IS FROM THE 4665 03:18:20,764 --> 03:18:22,600 CRISPR PAPER FROM THE NEW 4666 03:18:22,600 --> 03:18:23,701 ENGLAND JOURNAL AND IN CONTRAST 4667 03:18:23,701 --> 03:18:29,940 BECAUSE OF THE LOSS OF CELLS 4668 03:18:29,940 --> 03:18:33,077 DURING EDITING APHERESIS WAS UP 4669 03:18:33,077 --> 03:18:35,012 TO THREE CONSECUTIVE DAYS FOR 4670 03:18:35,012 --> 03:18:44,688 EACH CYCLE AND BOTH COHORTS 4671 03:18:44,688 --> 03:18:47,758 REQUIRED THE MOBILIZATION CYCLE. 4672 03:18:47,758 --> 03:18:49,693 THERE'S A DRAMATIC DIFFERENT 4673 03:18:49,693 --> 03:18:50,995 BETWEEN THE PROCEDURE AND THE 4674 03:18:50,995 --> 03:18:53,664 TIME IT TAKES TO GENERATE THE 4675 03:18:53,664 --> 03:18:55,533 CELLS WE NEED FOR MANUFACTURING 4676 03:18:55,533 --> 03:18:59,003 WHEN YOUR DOING GENE EDITING FOR 4677 03:18:59,003 --> 03:19:01,505 THE LENTIVIRAL VECTOR 4678 03:19:01,505 --> 03:19:02,573 TRANSDUCTION AND WE'VE HAD YEARS 4679 03:19:02,573 --> 03:19:12,316 NOW OF EXPERIENCE IN DOING. 4680 03:19:12,316 --> 03:19:15,519 AND YOU CAN SEE THE SUMMARY OF 4681 03:19:15,519 --> 03:19:17,922 EACH PATIENT OF TIME POINTS PRE 4682 03:19:17,922 --> 03:19:19,523 AND POST INFUSION. 4683 03:19:19,523 --> 03:19:23,427 OF THE 10 PATIENTS ONE OF THE 4684 03:19:23,427 --> 03:19:28,065 SUBJECTS HAD A MUTATION PRESENT 4685 03:19:28,065 --> 03:19:31,201 AT LOW LEVEL BEFORE COLLECTION. 4686 03:19:31,201 --> 03:19:33,337 IT WAS BELOW FROM THE CLIA 4687 03:19:33,337 --> 03:19:35,773 STANDPOINT BUT ONCE WE FOUND THE 4688 03:19:35,773 --> 03:19:36,974 MUTATION AFTER THE INCLUSION 4689 03:19:36,974 --> 03:19:39,910 OCCURRED WE WENT BECOME AND 4690 03:19:39,910 --> 03:19:40,978 VALIDATED IT IT WAS THERE BEFORE 4691 03:19:40,978 --> 03:19:41,645 HAND. 4692 03:19:41,645 --> 03:19:50,521 YOU CAN SEE THE MUTATION IN THE 4693 03:19:50,521 --> 03:19:54,425 DMAP3A GENE READILY SEEN 4694 03:19:54,425 --> 03:19:57,561 MUTATION IN HEMATOPOIESIS AND 4695 03:19:57,561 --> 03:20:00,264 REMAINS STABLE AND FOLLOW THE 4696 03:20:00,264 --> 03:20:01,765 PATIENTS CLOSELY AND WERE 4697 03:20:01,765 --> 03:20:03,534 HEALTHY AND NO ABNORMALITIES 4698 03:20:03,534 --> 03:20:05,102 WITH REGARD TO THEIR BONE MARROW 4699 03:20:05,102 --> 03:20:15,579 OR RESPONSE TO THE THERAPY. 4700 03:20:16,513 --> 03:20:20,217 AND YOU CAN LOOK CAREFULLY AT 4701 03:20:20,217 --> 03:20:23,587 THE NO INSERTION SITE AND 4702 03:20:23,587 --> 03:20:24,221 ABNORMALITIES ASSOCIATED WITH 4703 03:20:24,221 --> 03:20:26,624 THE GROWTH AND WE'VE SEEN NO 4704 03:20:26,624 --> 03:20:28,792 SIGNAL AT ALL IN ANY OF THESE 4705 03:20:28,792 --> 03:20:30,160 PATIENTS AT ANY TIME POINTS 4706 03:20:30,160 --> 03:20:30,361 SEEN. 4707 03:20:30,361 --> 03:20:37,501 TREMENDOUSLY SAFE SO FAR. 4708 03:20:37,501 --> 03:20:41,205 I WON'T GO IN THE DETAILS OF THE 4709 03:20:41,205 --> 03:20:48,078 EFFICACY OF THE TIME POINT AND 4710 03:20:48,078 --> 03:20:51,915 THERE'S LONG-TERM FOLLOW-UP BUT 4711 03:20:51,915 --> 03:20:53,484 YOU CAN SEE FETAL HEMOGLOBIN IS 4712 03:20:53,484 --> 03:20:58,489 ROBUST WITH THE ONE EXCEPTION 4713 03:20:58,489 --> 03:21:03,527 WITH THE BLUE ARROW 20% TO 40%. 4714 03:21:03,527 --> 03:21:06,263 THE PERCENT OF F CELLS IS HIGH, 4715 03:21:06,263 --> 03:21:07,531 BROAD AND STABLE OVER TIME. 4716 03:21:07,531 --> 03:21:12,036 EXCEPT FOR ONE PATIENT WITH A 4717 03:21:12,036 --> 03:21:14,872 LOW IN VIVO BCN BELOW .2. 4718 03:21:14,872 --> 03:21:19,677 ALL THE OTHER PATIENTS HAVE BTNs 4719 03:21:19,677 --> 03:21:21,278 ABOVE .3 AND GOOD INDUCTION AND 4720 03:21:21,278 --> 03:21:26,917 RESULTS FROM THE THERAPY. 4721 03:21:26,917 --> 03:21:34,091 SO THIS INITIAL PILOT RESULT 4722 03:21:34,091 --> 03:21:37,828 ALONG THE FOLLOW-UP NOW IS OVER 4723 03:21:37,828 --> 03:21:38,996 FOUR YEARS. 4724 03:21:38,996 --> 03:21:41,932 IT SEEMED SAFE AND GOOD 4725 03:21:41,932 --> 03:21:43,167 TRANSDUCTION AND NO EVENTS 4726 03:21:43,167 --> 03:21:50,974 RELATED TO THE VECTOR ITSELF. 4727 03:21:50,974 --> 03:21:54,278 AND THERE'S A HIGH CELL IN THE F 4728 03:21:54,278 --> 03:21:57,848 CELL AND SIGNIFICANT ATTENUATION 4729 03:21:57,848 --> 03:22:04,455 OF THE PHENOTYPE WITH MINIMUM 4730 03:22:04,455 --> 03:22:04,621 VCN. 4731 03:22:04,621 --> 03:22:06,590 IT DOESN'T HAVE TO BE THREE, 4732 03:22:06,590 --> 03:22:08,125 FOUR OR FIVE OR GET GOOD 4733 03:22:08,125 --> 03:22:08,392 INDUCTION. 4734 03:22:08,392 --> 03:22:12,496 IT'S MORE ONE TO TWO. 4735 03:22:12,496 --> 03:22:13,497 SO I WASN'T ASKED TO TALK ABOUT 4736 03:22:13,497 --> 03:22:15,199 THE PAPER BUT WANTED TO MENTION 4737 03:22:15,199 --> 03:22:20,804 THEM TO YOU AND POINT THEM OUT 4738 03:22:20,804 --> 03:22:21,271 TO YOU. 4739 03:22:21,271 --> 03:22:28,579 WE PUBLISHED A PAPER WITH OUR 4740 03:22:28,579 --> 03:22:29,713 COLLABORATOR ON SINGLE CELL 4741 03:22:29,713 --> 03:22:33,851 ANALYSIS COMPARING PATIENTS WITH 4742 03:22:33,851 --> 03:22:35,452 THE TRIAL WITH THE PROOF OF 4743 03:22:35,452 --> 03:22:40,390 BLOOD HEAVILY WITH HYDROXYUREA 4744 03:22:40,390 --> 03:22:42,659 AND LOOKED AT THE EFFECT OF 4745 03:22:42,659 --> 03:22:44,461 MANUFACTURING AND TRANSDUCTION 4746 03:22:44,461 --> 03:22:48,766 AND ENGRAFTMENT WHICH IS 4747 03:22:48,766 --> 03:22:50,167 ACTUALLY RELEVANT TO GENE 4748 03:22:50,167 --> 03:22:52,770 EDITING PROTOCOL AND LOOKED AT 4749 03:22:52,770 --> 03:22:58,842 THE MUTATION BURDEN OF THIS 4750 03:22:58,842 --> 03:22:59,409 MANUFACTURING ENGRAFTMENT 4751 03:22:59,409 --> 03:23:01,812 PROCEDURE AND WE'RE DOING A 4752 03:23:01,812 --> 03:23:03,781 STUDY FUNDED BY TO THE GATES 4753 03:23:03,781 --> 03:23:06,150 FOUNDATION LOOKING AT THE 4754 03:23:06,150 --> 03:23:10,554 LANDSCAPE IN SICKLE CELL DISEASE 4755 03:23:10,554 --> 03:23:12,589 PATIENTS COMPARED TO TANZANIA 4756 03:23:12,589 --> 03:23:17,795 AND U.K. AND BOSTON AND 4757 03:23:17,795 --> 03:23:20,497 DEVELOPING IN VIVO GENE 4758 03:23:20,497 --> 03:23:23,934 TECHNOLOGY USING NANO PARTICLES 4759 03:23:23,934 --> 03:23:26,203 AND ALSO USING VIRAL VECTORS AND 4760 03:23:26,203 --> 03:23:29,139 MODIFIED VIRAL VECTORS. 4761 03:23:29,139 --> 03:23:33,410 THE TRIAL I'LL TALK ABOUT IS 4762 03:23:33,410 --> 03:23:38,882 PART OF A LARGE SCALE GENOMIC 4763 03:23:38,882 --> 03:23:40,784 ANALYSIS AT BRIGHAM AND WOMEN'S 4764 03:23:40,784 --> 03:23:45,088 HOSPITAL. 4765 03:23:45,088 --> 03:23:47,691 SO THIS BROUGHT US TO THE GRAPH 4766 03:23:47,691 --> 03:23:52,729 STUDY WHICH IS THE PHASE 2 STUDY 4767 03:23:52,729 --> 03:23:55,032 TO REDUCE SICKLE PAIN IN A 4768 03:23:55,032 --> 03:24:04,775 PATIENT'S RECEIVING THE THERAPY. 4769 03:24:04,775 --> 03:24:06,743 TO WRAP UP QUICKLY THIS IS NINE 4770 03:24:06,743 --> 03:24:08,245 CENTERS HERE AND ALL THE SITES 4771 03:24:08,245 --> 03:24:11,048 ARE ACTIVATED WITH THE P.I.s 4772 03:24:11,048 --> 03:24:11,315 LISTED. 4773 03:24:11,315 --> 03:24:15,686 AND THE STUDY DESIGN IS OPEN 4774 03:24:15,686 --> 03:24:17,221 LABELLED AND ASKING CAN THE 4775 03:24:17,221 --> 03:24:20,290 SINGLE INFUSION OF THE CELLS 4776 03:24:20,290 --> 03:24:23,527 WITH THE VECTOR REDUCE PAIN IN 4777 03:24:23,527 --> 03:24:24,461 THE PATIENTS. 4778 03:24:24,461 --> 03:24:26,296 WE HAVE A SAMPLE SIZE OF 25 4779 03:24:26,296 --> 03:24:28,065 INFUSED PATIENTS AND THE TIME 4780 03:24:28,065 --> 03:24:29,900 LINE FOR ENROLLMENT TO INFUSION 4781 03:24:29,900 --> 03:24:33,103 AS YOU CAN SEE IS FROM 2022 TO 4782 03:24:33,103 --> 03:24:43,213 2024. 4783 03:24:44,281 --> 03:24:48,185 I WANT TO POINT OUT THE PILOT 4784 03:24:48,185 --> 03:24:50,787 STUDY. 4785 03:24:50,787 --> 03:25:01,164 WE INCLUDED EXCLUSION FOR CP AND 4786 03:25:01,164 --> 03:25:07,571 PRIAPRISM AND A SUPER NATENT AND 4787 03:25:07,571 --> 03:25:08,038 ADJUSTMENT OF MOY AND 4788 03:25:08,038 --> 03:25:12,476 INTERESTING RESULTS. 4789 03:25:12,476 --> 03:25:14,711 AND WE'RE CONTINUING OUR 4790 03:25:14,711 --> 03:25:20,083 MONITORING OF GENE PRE AND POST 4791 03:25:20,083 --> 03:25:26,957 INFUSION OF LEUKEMIA ASSOCIATE 4792 03:25:26,957 --> 03:25:31,328 ED POST INFUSION AND THREES AN 4793 03:25:31,328 --> 03:25:33,864 INDEPENDENT PANEL ADJUDICATING 4794 03:25:33,864 --> 03:25:37,868 ALL THE RESULTS WITHIN 72 HOURS 4795 03:25:37,868 --> 03:25:40,170 OF BEING UPLOADED. 4796 03:25:40,170 --> 03:25:42,639 QUICKLY, WHERE WE'RE AT. 4797 03:25:42,639 --> 03:25:47,511 WE MADE VERY GOOD PROGRESS. 4798 03:25:47,511 --> 03:25:49,713 THERE'S BEEN 31 CONSENTS, 4 4799 03:25:49,713 --> 03:25:52,783 SCREEN FAILURES AND 22 PATIENTS 4800 03:25:52,783 --> 03:25:54,618 CURRENTLY ON STUDY. 4801 03:25:54,618 --> 03:25:57,287 OF 22 ONE WITH DREW AND ONE 4802 03:25:57,287 --> 03:26:01,258 IMMOBILIZED AND OF THOSE REMAIN 4803 03:26:01,258 --> 03:26:03,493 13 INFUSED, TWO MANUFACTURED AND 4804 03:26:03,493 --> 03:26:09,032 FIVE STARTED TRANSFUSIONS AND 4805 03:26:09,032 --> 03:26:13,036 THERE'S FIVE CONSENTED AND 4806 03:26:13,036 --> 03:26:15,505 SCREENING PROGRESS AND COMPLETED 4807 03:26:15,505 --> 03:26:16,873 ACCRUAL ASSUMING ALL FIVE 4808 03:26:16,873 --> 03:26:19,209 PATIENTS IN THE SCREENING MAKE 4809 03:26:19,209 --> 03:26:22,012 IT INTO THE ACTUAL PROTOCOL. 4810 03:26:22,012 --> 03:26:24,982 SO FAR THERE'S BEEN NO SAFETY 4811 03:26:24,982 --> 03:26:27,985 SIGNALS OR CONCERNS TO DATE AND 4812 03:26:27,985 --> 03:26:30,287 NO SCREENED PATIENTS HAVE HAD 4813 03:26:30,287 --> 03:26:31,688 PATHOGEN BEING MUTATIONS TO 4814 03:26:31,688 --> 03:26:31,888 DATE. 4815 03:26:31,888 --> 03:26:34,191 SO FAR THE TRIAL HAS GONE QUITE 4816 03:26:34,191 --> 03:26:34,524 WELL. 4817 03:26:34,524 --> 03:26:36,393 IT'S A COMPLICATED TRIAL WITH 4818 03:26:36,393 --> 03:26:38,362 LOTS OF SITES AND MANUFACTURING 4819 03:26:38,362 --> 03:26:41,798 AND SO WE'RE VERY THRILLED WITH 4820 03:26:41,798 --> 03:26:44,501 THE PROGRESS WE'VE MADE AND HOPE 4821 03:26:44,501 --> 03:26:46,336 TO SEE EFFICACY RESULTS IN THE 4822 03:26:46,336 --> 03:26:51,274 NEXT TWO YEARS. 4823 03:26:51,274 --> 03:26:53,710 SO HUGE AMOUNT OF WORK FROM MANY 4824 03:26:53,710 --> 03:26:59,182 PEOPLE IN BOSTON LISTED HERE. 4825 03:26:59,182 --> 03:27:09,359 THIS IS FUNDED BY RO1 AT NIH AND 4826 03:27:09,359 --> 03:27:12,029 THE GATES FOUNDATION. 4827 03:27:12,029 --> 03:27:15,799 AND IN THE GRASP TRIAL MARK AND 4828 03:27:15,799 --> 03:27:22,139 I ARE CHAIRS AND MARIO EAPEN HAS 4829 03:27:22,139 --> 03:27:24,674 BEEN INSTRUMENTAL IN GETTING THE 4830 03:27:24,674 --> 03:27:26,977 TRIAL RUNNING AND THE MEDICAL 4831 03:27:26,977 --> 03:27:29,246 COLLEGE OF WISCONSIN AND THE 4832 03:27:29,246 --> 03:27:32,249 TRIAL BY DANA FARBER. 4833 03:27:32,249 --> 03:27:35,552 AND THE GENE EDITING PROGRAM AT 4834 03:27:35,552 --> 03:27:38,221 BOSTON'S CHILDREN HAS BEEN VERY 4835 03:27:38,221 --> 03:27:40,791 HELPFUL IN MANY DISEASES AND 4836 03:27:40,791 --> 03:27:42,092 HAVE BEEN AN INTEGRAL PART OF 4837 03:27:42,092 --> 03:27:42,692 THIS. 4838 03:27:42,692 --> 03:27:50,667 THANK YOU VERY MUCH. 4839 03:27:50,667 --> 03:27:51,868 >> ANY ONLINE QUESTIONS. 4840 03:27:51,868 --> 03:27:54,271 >> WE HAVE A FEW. 4841 03:27:54,271 --> 03:27:55,972 >> GIVEN THE TIME, DAVID, CAN 4842 03:27:55,972 --> 03:27:58,241 YOU PLEASE RESPOND TO THE ONLINE 4843 03:27:58,241 --> 03:27:58,508 QUESTIONS? 4844 03:27:58,508 --> 03:28:01,344 WE NEED TO MOVE ON HERE. 4845 03:28:01,344 --> 03:28:02,512 >> OKAY, SURE. 4846 03:28:02,512 --> 03:28:06,516 >> FOR THE SAKE OF THE PROGRAM. 4847 03:28:06,516 --> 03:28:12,089 SO, WE'LL MOVE ON TO THE NEXT 4848 03:28:12,089 --> 03:28:15,692 TALK FETAL HEMOGLOBIN 4849 03:28:15,692 --> 03:28:24,134 AUGMENTATION FOR NON-CYTOTOXIC 4850 03:28:24,134 --> 03:28:25,669 EPIGENETIC THERAPEUTICS. 4851 03:28:25,669 --> 03:28:26,136 >> THANK YOU FOR THE 4852 03:28:26,136 --> 03:28:30,674 OPPORTUNITY. 4853 03:28:30,674 --> 03:28:39,116 THESE ARE MY DISCLOSURES. 4854 03:28:39,116 --> 03:28:43,019 THIS IS NOT JUST TO IMPROVE THE 4855 03:28:43,019 --> 03:28:44,821 QUALITY OF LIFE BUT THE QUANTITY 4856 03:28:44,821 --> 03:28:46,990 OF LIFE AND ONE CLUE HOW YOU MAY 4857 03:28:46,990 --> 03:28:49,826 WANT TO ADDRESS THAT PROBLEM IS 4858 03:28:49,826 --> 03:28:51,695 ONE OF THE MOST IMPORTANT 4859 03:28:51,695 --> 03:28:53,296 PREDICTORS OF EARLY DEATH IN 4860 03:28:53,296 --> 03:28:56,066 ADULT COHORTS IS DECLINING 4861 03:28:56,066 --> 03:28:58,768 ABILITY TO COMPENSATE FOR THE 4862 03:28:58,768 --> 03:29:04,841 CHRONIC HEMOLYSIS THAT CAN BE 4863 03:29:04,841 --> 03:29:07,010 MEASURED BY HEMOGLOBIN LEVEL. 4864 03:29:07,010 --> 03:29:10,147 BASICALLY LESS THAN TENFOLD OF 4865 03:29:10,147 --> 03:29:11,114 THE COUNT. 4866 03:29:11,114 --> 03:29:14,050 AND ANOTHER CLUE IS TO LOOK AT 4867 03:29:14,050 --> 03:29:18,822 THE CHARACTERISTICS OF THE 4868 03:29:18,822 --> 03:29:19,523 PATIENTS. 4869 03:29:19,523 --> 03:29:23,527 THEY HAVE LOWER HEMOGLOBIN 4870 03:29:23,527 --> 03:29:27,264 LEVELS AND HIGHER SERUM 4871 03:29:27,264 --> 03:29:28,665 REACTANT. 4872 03:29:28,665 --> 03:29:31,635 AND UNFORTUNATELY THE DRUG WE 4873 03:29:31,635 --> 03:29:32,669 HAVE TRYING TO INCREASE THE 4874 03:29:32,669 --> 03:29:36,139 FETAL HEMOGLOBIN IS UNABLE TO 4875 03:29:36,139 --> 03:29:40,810 SUSTAIN THROUGH THAT FOR THE 4876 03:29:40,810 --> 03:29:41,211 PATIENTS. 4877 03:29:41,211 --> 03:29:46,483 WHAT YOU SEE HERE IS GRAPHS OF 4878 03:29:46,483 --> 03:29:47,784 FETAL HEMOGLOBIN OVER TIME AND 4879 03:29:47,784 --> 03:29:52,589 THE PATIENTS ONE THE LOWER FETAL 4880 03:29:52,589 --> 03:29:57,093 HEMOGLOBIN IS WHERE HIGH DROX 4881 03:29:57,093 --> 03:30:02,766 DROXY -- HYDROXYUREA WAS UNABLE 4882 03:30:02,766 --> 03:30:04,100 TO CHANGE AS SEEN IN THE GRAPH 4883 03:30:04,100 --> 03:30:05,735 ON THE RIGHT. 4884 03:30:05,735 --> 03:30:09,206 WE NEED OTHER WAYS OF INCREASING 4885 03:30:09,206 --> 03:30:09,606 FETAL HEMOGLOBIN. 4886 03:30:09,606 --> 03:30:12,242 YOU HEARD OF GENE THERAPY 4887 03:30:12,242 --> 03:30:16,613 TARGETING THE PROTEIN HUB 4888 03:30:16,613 --> 03:30:17,480 REPRESSING THE FETAL HEMOGLOBIN 4889 03:30:17,480 --> 03:30:21,117 GENES AND THE DNA BINDING FACTOR 4890 03:30:21,117 --> 03:30:22,886 BUT WE CAN POTENTIALLY USE SMALL 4891 03:30:22,886 --> 03:30:24,854 MOLECULES TO INHIBIT THE ENZYMES 4892 03:30:24,854 --> 03:30:29,492 BEING RECRUITED BY BCL11A AND 4893 03:30:29,492 --> 03:30:38,535 EVEN IDENTIFY THE ENZYMES. 4894 03:30:38,535 --> 03:30:44,407 IF WE PULL IT DOWN HERE WE CAN 4895 03:30:44,407 --> 03:30:47,143 USE AND IDENTIFY THE REPRESSING 4896 03:30:47,143 --> 03:30:49,479 ENZYMES WITHOUT MEDIATING THE 4897 03:30:49,479 --> 03:30:50,247 SILENCING OF THE FETAL 4898 03:30:50,247 --> 03:30:50,914 HEMOGLOBIN GENE. 4899 03:30:50,914 --> 03:30:55,018 NOT ALL THESE ENZYMES CAN BE 4900 03:30:55,018 --> 03:30:56,820 INHIBITED WITHOUT CAUSING 4901 03:30:56,820 --> 03:30:59,756 DEVASTATING EFFECTS TO SOLVE 4902 03:30:59,756 --> 03:31:00,924 PHYSIOLOGY BUT I'M GOING TO SHOW 4903 03:31:00,924 --> 03:31:04,527 YOU CLINICAL AND PRE-CLINICAL 4904 03:31:04,527 --> 03:31:08,798 PROOF OF PRINCIPLE TO INHIBIT 4905 03:31:08,798 --> 03:31:12,602 THE TRANSFERASE AND THE MARKER 4906 03:31:12,602 --> 03:31:22,646 AND CHG. 4907 03:31:22,646 --> 03:31:26,549 AND THIS IS THE MOLECULE. 4908 03:31:26,549 --> 03:31:29,286 IT EXTENSIVELY DESCRIBED THE 4909 03:31:29,286 --> 03:31:31,721 CHEMISTRY AND CELL PHYSIOLOGY 4910 03:31:31,721 --> 03:31:34,057 THAT ALLOWS US TO USE THE MOL 4911 03:31:34,057 --> 03:31:37,694 CALL TO TARGET WITHOUT 4912 03:31:37,694 --> 03:31:38,161 CYTOTOXICITY. 4913 03:31:38,161 --> 03:31:43,066 SO WE IDENTIFIED THE MINIMUM BIO 4914 03:31:43,066 --> 03:31:45,001 LOGICALLY AFFECTED DOSES AND USE 4915 03:31:45,001 --> 03:31:46,569 THEM TO TREAT PATIENTS. 4916 03:31:46,569 --> 03:31:49,606 MANY OF WHOM ARE IN THE COHORTS 4917 03:31:49,606 --> 03:31:58,315 FROM THE TRIAL WHERE HYDROXYUREA 4918 03:31:58,315 --> 03:32:00,583 WAS ABLE TO INCREASE FETAL AND 4919 03:32:00,583 --> 03:32:03,787 TOTAL HEMOGLOBIN AS YOU SEE IN 4920 03:32:03,787 --> 03:32:07,557 THE GRAPHS AND THE MEASUREMENTS 4921 03:32:07,557 --> 03:32:15,365 WERE FOUR WEEKS AND EIGHT WEEKS. 4922 03:32:15,365 --> 03:32:19,035 THIS GRAPH IS SHOWING WE COULD 4923 03:32:19,035 --> 03:32:21,338 PRODUCE WITH THIS STRATEGY FETAL 4924 03:32:21,338 --> 03:32:24,808 HEMOGLOBIN INCREASES IN THE 4925 03:32:24,808 --> 03:32:27,711 PATIENTS WHERE HYDROXYUREA WERE 4926 03:32:27,711 --> 03:32:29,679 UNABLE AND ON THE RIGHT IS WHERE 4927 03:32:29,679 --> 03:32:31,781 IT WORKED FOR A WHILE AND 4928 03:32:31,781 --> 03:32:32,615 DISCONTINUED FOR WHATEVER REASON 4929 03:32:32,615 --> 03:32:36,786 AND ALSO THIS APPROACH WAS VERY 4930 03:32:36,786 --> 03:32:41,458 EFFICACIOUS. 4931 03:32:41,458 --> 03:32:45,228 SO TO IMPROVE THE ACCESSIBILITY 4932 03:32:45,228 --> 03:32:47,997 AND POSSIBILITY OF USING THIS 4933 03:32:47,997 --> 03:32:50,867 APPROACH WORLDWIDE AND 4934 03:32:50,867 --> 03:32:52,869 SUSTAINABLE IN AN ACCESSIBLE WAY 4935 03:32:52,869 --> 03:32:58,641 WE SPENT TIME CONVERTING THE 4936 03:32:58,641 --> 03:32:59,909 THERAPY AND IDENTIFIED THE 4937 03:32:59,909 --> 03:33:04,481 MINIMUM EFFECTIVE DOSE OF THE 4938 03:33:04,481 --> 03:33:08,785 ORAL THERAPY TO TARGET AND THIS 4939 03:33:08,785 --> 03:33:11,688 IS THE FIRST LONG-TERM 4940 03:33:11,688 --> 03:33:14,391 DEMONSTRATION OF A SUSTAINABLE 4941 03:33:14,391 --> 03:33:15,024 INCREASE IN FETAL HEMOGLOBIN. 4942 03:33:15,024 --> 03:33:19,062 THIS RANDOMIZED THE PATIENTS TO 4943 03:33:19,062 --> 03:33:23,666 RECEIVE VITAMIN B3 ALONE OR ORAL 4944 03:33:23,666 --> 03:33:27,404 TARGETING AGENT FOR 12 WEEK AND 4945 03:33:27,404 --> 03:33:30,907 RECEIVED A COMBINATION THERAPY. 4946 03:33:30,907 --> 03:33:33,643 THERE'S ONE PATIENT IN WHOM THE 4947 03:33:33,643 --> 03:33:37,280 DOSE OF THE TARGETED THERAPY WAS 4948 03:33:37,280 --> 03:33:40,483 BELOW THE MINIMUM BIO LOGICALLY 4949 03:33:40,483 --> 03:33:42,619 EFFECTIVE DOSE BECAUSE OF HIGH 4950 03:33:42,619 --> 03:33:44,788 BODY WEIGHT NOT ANTICIPATED IN 4951 03:33:44,788 --> 03:33:48,792 THE PROTOCOL AND BASICALLY WE 4952 03:33:48,792 --> 03:33:52,796 WERE WORKING WITH THE MINIMUM 4953 03:33:52,796 --> 03:33:57,767 EFFECTIVE DOSE AND SUSTAINABLE 4954 03:33:57,767 --> 03:33:58,968 FETAL HEMOGLOBIN INCREASES IN 4955 03:33:58,968 --> 03:34:07,076 THE 1 TO 2 GRAM PER DECILITER 4956 03:34:07,076 --> 03:34:09,145 RANGE. 4957 03:34:09,145 --> 03:34:11,047 AND BECAUSE WE TREATED THESE 4958 03:34:11,047 --> 03:34:12,415 PATIENTS FOR ABOUT A YEAR, IT 4959 03:34:12,415 --> 03:34:15,084 GAVE US ENOUGH TIME TO LOOK AT 4960 03:34:15,084 --> 03:34:16,553 CRISIS FREQUENCY. 4961 03:34:16,553 --> 03:34:20,457 THESE PATIENTS WERE AGAIN 4962 03:34:20,457 --> 03:34:22,492 HYDROXY REFRACTORY MOST IN THE 4963 03:34:22,492 --> 03:34:23,860 CATEGORY OF PATIENTS AT RISK 4964 03:34:23,860 --> 03:34:26,596 ALMOST ALL OF THEM FOR EARLY 4965 03:34:26,596 --> 03:34:28,731 DEATH SO THERE'S COMPLICATIONS 4966 03:34:28,731 --> 03:34:29,199 AT BASELINE. 4967 03:34:29,199 --> 03:34:31,568 VERY FREQUENT ADMISSIONS IN THE 4968 03:34:31,568 --> 03:34:34,804 YEAR PRIOR TO THE THERAPY AND 4969 03:34:34,804 --> 03:34:37,006 THE CRISIS FREQUENCY WAS 4970 03:34:37,006 --> 03:34:38,541 SIGNIFICANTLY REDUCED IN THE 4971 03:34:38,541 --> 03:34:48,485 YEAR ON THIS THERAPY. 4972 03:34:48,485 --> 03:34:51,087 THAT WAS CLINICAL PROOF OF 4973 03:34:51,087 --> 03:34:53,189 PRINCIPLE FOR PATIENTS WITH THE 4974 03:34:53,189 --> 03:34:56,326 HIGHEST RISK OF EARLY DEATH AND 4975 03:34:56,326 --> 03:35:00,263 SHOW PROOF OF PRINCIPLE WE CAN 4976 03:35:00,263 --> 03:35:01,664 TARGET ANOTHER TAR GET AND THAT 4977 03:35:01,664 --> 03:35:08,805 IS THE ATP CHROMATIN REMODELS 4978 03:35:08,805 --> 03:35:11,274 REPOSITION NUCLEOSOMES. 4979 03:35:11,274 --> 03:35:13,142 AT TO THE BUSINESS END OF 4980 03:35:13,142 --> 03:35:15,144 EPIGENETICS AND THERE WERE NO 4981 03:35:15,144 --> 03:35:16,412 SMALL MOLECULES TO INHIBIT THE 4982 03:35:16,412 --> 03:35:18,815 ENZYMES SO WE DEVELOPED ONE. 4983 03:35:18,815 --> 03:35:24,821 AND THESE MOLECULES ARE NOT NON 4984 03:35:24,821 --> 03:35:26,789 CYTOTOXIC AND YOU CAN LOOK AT 4985 03:35:26,789 --> 03:35:30,226 THE VIABILITY OF HEALTHY HUMAN 4986 03:35:30,226 --> 03:35:33,897 CD 34 POSITIVE PROGENITOR CELLS. 4987 03:35:33,897 --> 03:35:35,965 THEY DON'T ACTIVATE THE FLOW 4988 03:35:35,965 --> 03:35:39,435 DATA YOU SEE HERE AND THE COLONY 4989 03:35:39,435 --> 03:35:42,805 FORMING ASSAY DATA WE DON'T SEE 4990 03:35:42,805 --> 03:35:47,043 A SIGNIFICANT DECREASE AND 4991 03:35:47,043 --> 03:35:48,745 POSITIVE CONTROL. 4992 03:35:48,745 --> 03:35:54,083 AND THESE MOLECULES ARE ABLE TO 4993 03:35:54,083 --> 03:35:56,619 INCREASE FETAL HEMOGLOBIN EVEN 4994 03:35:56,619 --> 03:36:00,290 IN HEMATOPOIETIC PROGENITOR 4995 03:36:00,290 --> 03:36:04,460 CELLS AND IN THE IN VITRO STUDY 4996 03:36:04,460 --> 03:36:09,265 WE SEE SEVERAL FOLD INCREASE IN 4997 03:36:09,265 --> 03:36:11,301 FETAL HEMOGLOBIN. 4998 03:36:11,301 --> 03:36:13,803 SO I GUESS PART OF THE PROBLEM 4999 03:36:13,803 --> 03:36:17,740 I'M ALLUDING TO IS THE 5000 03:36:17,740 --> 03:36:20,443 DIMINISHED PROGENITOR CELL IN 5001 03:36:20,443 --> 03:36:22,545 THE BONE MARROW THAT COULD BE 5002 03:36:22,545 --> 03:36:25,548 MEASURED SHOWN IN THE GRAPHS ON 5003 03:36:25,548 --> 03:36:29,252 THE LEFT THE FIRST VASO 5004 03:36:29,252 --> 03:36:29,919 OCCLUSION IS ONE FACTOR AND 5005 03:36:29,919 --> 03:36:33,823 DAMAGE CONTRIBUTING TO THE 5006 03:36:33,823 --> 03:36:36,793 DECLINE OF THE SITE AND ANOTHER 5007 03:36:36,793 --> 03:36:38,995 FACTOR IS THE STRESS IN THE BONE 5008 03:36:38,995 --> 03:36:40,797 MARROW THAT DEPLETES 5009 03:36:40,797 --> 03:36:43,132 MITOCHONDRIAL OUTPUTS SUCH AS 5010 03:36:43,132 --> 03:36:48,805 NAD AND NAD IS A CO-FACTOR FOR 5011 03:36:48,805 --> 03:36:53,576 EPIGENETIC ENZYMES THAT MEDIATE 5012 03:36:53,576 --> 03:36:55,545 HEMATOPOIETIC STEM CELL HEALTH 5013 03:36:55,545 --> 03:36:57,680 AND THAT'S PART OF THE RATIONALE 5014 03:36:57,680 --> 03:36:59,315 WHY WE INCLUDED IT IN THE 5015 03:36:59,315 --> 03:37:05,755 PROBLEM WE SHOWED EARLIER. 5016 03:37:05,755 --> 03:37:08,257 SO THIS IS MY FINAL SLIDE. 5017 03:37:08,257 --> 03:37:13,696 ONE ASPECT WE HAVE TO DEAL WITH 5018 03:37:13,696 --> 03:37:15,765 IS STRATEGIES TO INCREASE FETAL 5019 03:37:15,765 --> 03:37:17,834 HEMOGLOBIN AND IT CAN BE DONE 5020 03:37:17,834 --> 03:37:22,939 WITH SMALL MOLECULES THAT TARGET 5021 03:37:22,939 --> 03:37:28,211 ENZYMES IN THE BCL11A ITSELF. 5022 03:37:28,211 --> 03:37:34,417 WE SHOULDN'T NEGLECT IT'S NOT 5023 03:37:34,417 --> 03:37:35,952 JUST THE HEMOGLOBIN ACCESS 5024 03:37:35,952 --> 03:37:38,354 CONTRIBUTING TO ANEMIA LEADING 5025 03:37:38,354 --> 03:37:42,725 TO EARLY DEATH THERE'S INDIRECT 5026 03:37:42,725 --> 03:37:43,226 CONSEQUENCES. 5027 03:37:43,226 --> 03:37:46,863 THE DAMAGE AND REDUX STRESS AND 5028 03:37:46,863 --> 03:37:48,564 THE DEPLETION OF IMPORTANT 5029 03:37:48,564 --> 03:37:51,601 METABOLIC COFACTORS NEEDED FOR 5030 03:37:51,601 --> 03:37:56,806 PROGENITOR HEALTH AND THESE ARE 5031 03:37:56,806 --> 03:37:59,409 ALL POTENTIALLY REMEDIABLE. 5032 03:37:59,409 --> 03:38:01,411 I'D LIKE TO THANK THE FUNDERS 5033 03:38:01,411 --> 03:38:04,781 AND THE PATIENTS. 5034 03:38:04,781 --> 03:38:15,124 THANK YOU VERY MUCH. 5035 03:38:23,132 --> 03:38:24,801 >> ANY QUESTIONS? 5036 03:38:24,801 --> 03:38:26,102 NO ONLINE QUESTIONS? 5037 03:38:26,102 --> 03:38:26,302 OKAY. 5038 03:38:26,302 --> 03:38:34,377 THANK YOU. 5039 03:38:34,377 --> 03:38:38,414 SO OUR NEXT TALK IS FOR SICKLE 5040 03:38:38,414 --> 03:38:42,885 CELL DISEASE AND CARDIOVASCULAR 5041 03:38:42,885 --> 03:38:49,192 RISK-RED CELL EXCHANGE TRIAL AND 5042 03:38:49,192 --> 03:38:50,159 MARIA BROOKS UNIVERSITY OF 5043 03:38:50,159 --> 03:38:50,727 PITTSBURGH IS GOING TO TALK 5044 03:38:50,727 --> 03:38:52,161 ABOUT THIS. 5045 03:38:52,161 --> 03:38:54,731 GO AHEAD, MARIA. 5046 03:38:54,731 --> 03:38:55,231 >> OKAY. 5047 03:38:55,231 --> 03:38:56,265 NEXT SLIDE, PLEASE. 5048 03:38:56,265 --> 03:38:58,868 IT'S MY PRIVILEGE TO SPEAK TO 5049 03:38:58,868 --> 03:39:06,576 YOU ABOUT WHAT WE CALL THE SCD 5050 03:39:06,576 --> 03:39:07,276 CARRE TRIAL. 5051 03:39:07,276 --> 03:39:09,278 IT'S DONE IN COLLABORATION WITH 5052 03:39:09,278 --> 03:39:10,246 OUR CLINICAL COORDINATING CENTER 5053 03:39:10,246 --> 03:39:12,281 WHICH IS RUN THROUGH THE 5054 03:39:12,281 --> 03:39:15,184 UNIVERSITY OF MARYLAND WITH 5055 03:39:15,184 --> 03:39:16,185 DR. GLADWIN AND THE UNIVERSITY 5056 03:39:16,185 --> 03:39:21,357 OF PITTSBURGH. 5057 03:39:21,357 --> 03:39:25,428 WE'RE FORTUNATE TO BE FUNDED 5058 03:39:25,428 --> 03:39:27,263 THROUGH NHLBI THROUGH THE BLOOD 5059 03:39:27,263 --> 03:39:28,097 DIVISION AND A WONDERFUL 5060 03:39:28,097 --> 03:39:29,866 COLLABORATION AND WE HAVE 5061 03:39:29,866 --> 03:39:31,200 COLLEAGUES FROM UNIVERSITY OF 5062 03:39:31,200 --> 03:39:32,201 ILLINOIS AND PITTSBURGH. 5063 03:39:32,201 --> 03:39:34,203 THE TRIAL INCLUDES AN ALL-STAR 5064 03:39:34,203 --> 03:39:37,840 CAST OF SITES AND EACH SITE IS A 5065 03:39:37,840 --> 03:39:41,344 COLLABORATION BETWEEN THE 5066 03:39:41,344 --> 03:39:43,146 HEMATOLOGY CARE OF SICKLE CELL 5067 03:39:43,146 --> 03:39:45,248 PATIENTS AND THE ATRANSFUSION 5068 03:39:45,248 --> 03:39:46,282 MEDICINE FOLKS AND WORKING 5069 03:39:46,282 --> 03:39:46,916 TOGETHER TO DESIGN AND IMPLEMENT 5070 03:39:46,916 --> 03:39:49,352 THE TRIAL. 5071 03:39:49,352 --> 03:39:51,521 EFFECTIVELY THIS IS AGAIN A 5072 03:39:51,521 --> 03:39:54,090 RANDOMIZED PARALLEL TWO-ARM 5073 03:39:54,090 --> 03:39:55,258 CLINICAL TRIAL WHERE PATIENTS 5074 03:39:55,258 --> 03:39:57,527 ARE ASSIGNED TO EITHER STANDARD 5075 03:39:57,527 --> 03:40:00,363 OF CARE OR STANDARD OF CARE PLUS 5076 03:40:00,363 --> 03:40:01,664 EXCHANGE TRANSFUSION. 5077 03:40:01,664 --> 03:40:04,000 IT'S A 12-MONTH INTERVENTION 5078 03:40:04,000 --> 03:40:08,805 PLUS ANOTHER ONE-MONTH OF FOLLOW 5079 03:40:08,805 --> 03:40:10,139 UP WHERE WE'LL ASSESS OUTCOMES. 5080 03:40:10,139 --> 03:40:14,644 WE DID HAVE TO EXTEND ENROLLMENT 5081 03:40:14,644 --> 03:40:17,580 FOR ONE YEAR AND HAD TO GO TO 5082 03:40:17,580 --> 03:40:19,248 OUR NO-COST EXTENSION PERIOD BUT 5083 03:40:19,248 --> 03:40:22,084 DOING WELL WITH ENROLLMENT. 5084 03:40:22,084 --> 03:40:25,922 THE TARGET IS 150 PARTICIPANTS 5085 03:40:25,922 --> 03:40:29,091 RANDOMIZED IN THE AND WE'RE AT 5086 03:40:29,091 --> 03:40:29,358 129. 5087 03:40:29,358 --> 03:40:31,928 WE ANTICIPATE ENROLLMENT WILL BE 5088 03:40:31,928 --> 03:40:36,799 COMPLETED IN DECEMBER OF THIS 5089 03:40:36,799 --> 03:40:38,401 YEAR AND AN EXTRA YEAR OF 5090 03:40:38,401 --> 03:40:40,803 FOLLOW-UP AT BEGINNING OF 2026 5091 03:40:40,803 --> 03:40:43,239 WE SHOULD PUT TOGETHER THE DATA 5092 03:40:43,239 --> 03:40:44,740 FOR THE TRIAL. 5093 03:40:44,740 --> 03:40:46,709 SO JUST TO REMIND YOU, I KNOW 5094 03:40:46,709 --> 03:40:48,811 THIS TRIAL HAS BEEN PRESENTED A 5095 03:40:48,811 --> 03:40:49,946 COUPLE TIMES AT THIS MEETING BUT 5096 03:40:49,946 --> 03:40:56,118 THIS IS A TRIAL WHERE WE'RE 5097 03:40:56,118 --> 03:40:58,387 LOOKING AT AUTOMATED CELL 5098 03:40:58,387 --> 03:40:59,722 TRANSFUSION PLUS STANDARD OF 5099 03:40:59,722 --> 03:41:00,623 CAIRO OPPOSED TO STANDARD OF 5100 03:41:00,623 --> 03:41:04,260 CARE ALONE AND LOOKING AT 5101 03:41:04,260 --> 03:41:07,296 EPISODES OF WORSENING OF SICKLE 5102 03:41:07,296 --> 03:41:08,497 CELL DISEASE REQUIRING AN ACUTE 5103 03:41:08,497 --> 03:41:11,767 HEALTH CARE ENCOUNTER ORE RESULT 5104 03:41:11,767 --> 03:41:14,704 IN DEATH AMONG HIGH-RISK ADULT 5105 03:41:14,704 --> 03:41:15,304 SICKLE CELL DISEASE PATIENTS. 5106 03:41:15,304 --> 03:41:17,506 THE SECONDARY AIM IS TO EVALUATE 5107 03:41:17,506 --> 03:41:24,180 THE ADDITION OF AUTOMATED RED 5108 03:41:24,180 --> 03:41:25,281 BLOOD CELL AND LOOKING AT 5109 03:41:25,281 --> 03:41:27,350 QUALITY OF LIFE AND PAIN AS WELL 5110 03:41:27,350 --> 03:41:34,490 AS LOOKING AT SAFETY OUTCOMES. 5111 03:41:34,490 --> 03:41:36,259 IT'S A POPULATION INTERVENTION 5112 03:41:36,259 --> 03:41:37,026 AND OUTCOME AND I'LL BRIEFLY GO 5113 03:41:37,026 --> 03:41:39,128 THROUGH THAT. 5114 03:41:39,128 --> 03:41:41,264 THESE ARE OF COURSE ALL 5115 03:41:41,264 --> 03:41:42,064 PARTICIPANTS WHO HAVE SICKLE 5116 03:41:42,064 --> 03:41:42,431 CELL DISEASE. 5117 03:41:42,431 --> 03:41:44,033 THEY ARE ADULTS. 5118 03:41:44,033 --> 03:41:46,135 THEY COULD NOT HAVE BEEN ON 5119 03:41:46,135 --> 03:41:47,904 CHRONIC EXCHANGE TRANSFUSION IN 5120 03:41:47,904 --> 03:41:49,939 THE PAST 60 DAYS AND THEY HAVE 5121 03:41:49,939 --> 03:41:52,808 TO HAVE A STABLE DOSE FOR THEIR 5122 03:41:52,808 --> 03:41:53,009 DRUGS. 5123 03:41:53,009 --> 03:41:54,810 MOST IMPORTANTLY THEY ARE 5124 03:41:54,810 --> 03:41:58,047 DEFINED AS HIGH RISK AS EITHER 5125 03:41:58,047 --> 03:41:59,916 HAVING PULMONARY HYPERTENSION AS 5126 03:41:59,916 --> 03:42:04,921 DEFINED BY THE TRV OR CHRONIC 5127 03:42:04,921 --> 03:42:10,092 KIDNEY DISEASE USING EF GFR OR 5128 03:42:10,092 --> 03:42:10,259 ACR. 5129 03:42:10,259 --> 03:42:15,264 THE EXCLUDE PATIENTS WHO WOULD 5130 03:42:15,264 --> 03:42:21,470 HAVE RED BLOOD CELL 5131 03:42:21,470 --> 03:42:23,706 ALLOIMMUNIZATION OR SEVERE 5132 03:42:23,706 --> 03:42:25,174 TRANSFUSION REACTIONS AND ANYONE 5133 03:42:25,174 --> 03:42:27,176 WHO HAD A STROKE WITHIN THE LAST 5134 03:42:27,176 --> 03:42:37,653 SIX MONTHS IS ALSO EXCLUDED. 5135 03:42:47,697 --> 03:42:50,566 AND WE LOOK AT ANTIBIOTICS AND 5136 03:42:50,566 --> 03:42:51,600 TRANSFUSIONS IF THEY'RE 5137 03:42:51,600 --> 03:42:52,935 CLINICALLY INDICATED. 5138 03:42:52,935 --> 03:42:55,304 TRANSFUSIONS ARE ALLOWED EVEN IN 5139 03:42:55,304 --> 03:42:57,106 STANDARD OF CARE. 5140 03:42:57,106 --> 03:43:03,212 WHAT WE'RE -- AND THESE 5141 03:43:03,212 --> 03:43:04,647 STANDARDS ARE FROM NHLBI, 5142 03:43:04,647 --> 03:43:06,515 AMERICAN THORACIC SOCIETY AND 5143 03:43:06,515 --> 03:43:10,386 AMERICAN SOCIETY OF HEMATOLOGY. 5144 03:43:10,386 --> 03:43:11,520 WHAT WE'RE CONTRASTING IT WITH 5145 03:43:11,520 --> 03:43:14,790 IS THE SAME STANDARD OF CARE BUT 5146 03:43:14,790 --> 03:43:16,492 THE ADDITION OF RED BLOOD CELL 5147 03:43:16,492 --> 03:43:18,094 EXCHANGE TRANSFUSIONS. 5148 03:43:18,094 --> 03:43:21,063 THE PROTOCOL IS STRUCTURED SUCH 5149 03:43:21,063 --> 03:43:23,065 THE PARTICIPANT WOULD COME IN 5150 03:43:23,065 --> 03:43:24,066 AND HAVE A TRANSFUSION EVERY 5151 03:43:24,066 --> 03:43:25,001 THREE TO SIX WEEKS. 5152 03:43:25,001 --> 03:43:29,472 THE GOAL IS TO HAVE THE 5153 03:43:29,472 --> 03:43:31,941 HEMOGLOBIN LEVELS BELOW 20% AND 5154 03:43:31,941 --> 03:43:33,809 THEN RE-TRANSFUSE IF THEY GOT 5155 03:43:33,809 --> 03:43:35,344 ABOVE 30%. 5156 03:43:35,344 --> 03:43:38,948 IN ADDITION, WE HAVE A TARGET 5157 03:43:38,948 --> 03:43:46,389 HEMOGLOBIN LEVEL OF 10 GRAMS PER 5158 03:43:46,389 --> 03:43:46,722 DECILITER. 5159 03:43:46,722 --> 03:43:49,025 THE END POINT ARE ACUTE HEALTH 5160 03:43:49,025 --> 03:43:50,893 CARE ENCOUNTERS OR DEATHS OVER 5161 03:43:50,893 --> 03:43:59,702 THE 13 MONTHS OF FOLLOW-UP. 5162 03:43:59,702 --> 03:44:04,306 AND WE'RE LOOKING FROM BEST TO 5163 03:44:04,306 --> 03:44:05,241 WORSE WHICH INCLUDES DEATH AS 5164 03:44:05,241 --> 03:44:09,478 WELL AS THE MAJOR COMPLICATIONS 5165 03:44:09,478 --> 03:44:12,782 WE'RE INTERESTED IN STROKE, 5166 03:44:12,782 --> 03:44:20,790 ACUTE KIDNEY LEVER OR ACUTE 5167 03:44:20,790 --> 03:44:26,362 CHEST SYNDROME AND THE SECONDARY 5168 03:44:26,362 --> 03:44:31,067 END POINTS INCLUDE EXERCISE 5169 03:44:31,067 --> 03:44:33,469 CAPACITY, CARDIOVASCULAR 5170 03:44:33,469 --> 03:44:43,279 FUNCTION, CARDIOVASCULAR RISK 5171 03:44:43,279 --> 03:44:44,346 BIOMARKERS AND PAIN. 5172 03:44:44,346 --> 03:44:46,482 AGAIN, I'M A STATISTICIAN. 5173 03:44:46,482 --> 03:44:47,850 I RUN THE DATA COORDINATING 5174 03:44:47,850 --> 03:44:50,786 CENTER AND I THOUGHT SINCE I WAS 5175 03:44:50,786 --> 03:44:52,188 TALKING TO YOU I'D TALK ABOUT 5176 03:44:52,188 --> 03:44:54,256 WHAT PLAGUES US WHEN WE'RE 5177 03:44:54,256 --> 03:44:55,458 TRYING TO THINK OF DESIGNING 5178 03:44:55,458 --> 03:44:57,226 TRIALS PARTICULARLY AT THE RARE 5179 03:44:57,226 --> 03:45:00,963 DISEASE SETTINGS WHERE WE KNOW 5180 03:45:00,963 --> 03:45:02,531 WE DON'T HAVE MUCH PARTICIPANTS 5181 03:45:02,531 --> 03:45:04,200 AND WANT TO MAKE THE MOST FROM 5182 03:45:04,200 --> 03:45:05,201 THE INFORMATION WE GET FROM THE 5183 03:45:05,201 --> 03:45:06,502 TRIAL. 5184 03:45:06,502 --> 03:45:08,370 I WANTED TO FOCUS BRIEFLY ON TWO 5185 03:45:08,370 --> 03:45:10,206 ELEMENTS WHICH IS HOW WE THINK 5186 03:45:10,206 --> 03:45:12,041 ABOUT THE RANDOMIZATION AND HOW 5187 03:45:12,041 --> 03:45:14,343 WE THINK ABOUT SELECTING TRIAL 5188 03:45:14,343 --> 03:45:15,878 END POINTS AND ANALYSIS 5189 03:45:15,878 --> 03:45:16,946 STRATEGIES IN ORDER TO OPTIMIZE 5190 03:45:16,946 --> 03:45:18,747 THE POWER AND GET THE MOST 5191 03:45:18,747 --> 03:45:20,216 INFORMATION THAT WE CAN FROM THE 5192 03:45:20,216 --> 03:45:26,889 DATA WE GET IN A TRIAL. 5193 03:45:26,889 --> 03:45:29,458 WE HAVE AN ADAPTIVE 5194 03:45:29,458 --> 03:45:31,193 RANDOMIZATION RANDOMIZE 5195 03:45:31,193 --> 03:45:32,561 PARTICIPANTS TO EXCHANGE OR 5196 03:45:32,561 --> 03:45:34,997 STANDARD OF CARE IN A ONE TO ONE 5197 03:45:34,997 --> 03:45:39,502 RATIO AND BALANCE THE 5198 03:45:39,502 --> 03:45:42,171 RANDOMIZATION AS BEST AS WE CAN 5199 03:45:42,171 --> 03:45:43,772 WITHIN THE 150 PARTICIPANT. 5200 03:45:43,772 --> 03:45:49,345 WE'RE GOING TO USE AN INDIVIDUAL 5201 03:45:49,345 --> 03:45:53,549 PARTICIPANT COVARIATE ADAPTIVE 5202 03:45:53,549 --> 03:45:55,918 RANDOMIZATION AND THE IDEA IS 5203 03:45:55,918 --> 03:45:57,119 EACH INDIVIDUAL IS RANDOMIZED 5204 03:45:57,119 --> 03:45:59,755 AND OUR GOAL IS TO HAVE THE SAME 5205 03:45:59,755 --> 03:46:01,524 NUMBER IN EACH INTERVENTION 5206 03:46:01,524 --> 03:46:02,992 GROUP AS WELL AS TO BALANCE EACH 5207 03:46:02,992 --> 03:46:05,494 OF THE FOLLOWING COVARIANTS. 5208 03:46:05,494 --> 03:46:07,596 SO WE'RE INTERESTED BEFORE THEY 5209 03:46:07,596 --> 03:46:11,500 ARE RANDOMIZED AND UNDERSTANDING 5210 03:46:11,500 --> 03:46:16,338 THEY'RE HYDROXYUREA USE AND 5211 03:46:16,338 --> 03:46:19,575 CHRONIC KIDNEY DISEASE, SEX, 5212 03:46:19,575 --> 03:46:20,876 HEMOGLOBIN GENOTYPE AND THE 5213 03:46:20,876 --> 03:46:21,510 CLINICAL SITE. 5214 03:46:21,510 --> 03:46:25,381 HERE AGAIN YOU CAN TWO THROUGH A 5215 03:46:25,381 --> 03:46:26,382 COUPLE ADVANCEMENT. 5216 03:46:26,382 --> 03:46:28,317 WE TAKE THE QUALITY OF EACH 5217 03:46:28,317 --> 03:46:33,689 PARTICIPANT BEFORE THEY'RE 5218 03:46:33,689 --> 03:46:33,989 RANDOMIZED. 5219 03:46:33,989 --> 03:46:36,692 WE LOOK AT THE BALANCE FOR EACH 5220 03:46:36,692 --> 03:46:37,826 OF THE CHARACTERISTICS. 5221 03:46:37,826 --> 03:46:40,229 AND WHAT WE DO IS WE SAY WHAT 5222 03:46:40,229 --> 03:46:43,199 HAPPENS IF THEY ARE ENROLL AND 5223 03:46:43,199 --> 03:46:44,400 ASSIGNED TO RED BLOOD CELL. 5224 03:46:44,400 --> 03:46:45,868 WHAT HAPPENS IF THEY'RE ENROLLED 5225 03:46:45,868 --> 03:46:48,204 TO STANDARD OF CARE? 5226 03:46:48,204 --> 03:46:52,641 NEXT AND NEXT AND WHAT WE FIND 5227 03:46:52,641 --> 03:46:53,976 IS THAT HOW IN BALANCE WOULD 5228 03:46:53,976 --> 03:46:59,048 THEY BE IN EACH OF THE 5229 03:46:59,048 --> 03:47:04,086 SITUATIONS AND CREATE THE METRIC 5230 03:47:04,086 --> 03:47:05,688 AND BY COMPARING THE IMBALANCE 5231 03:47:05,688 --> 03:47:07,656 IF THEY WERE RANDOMIZED TO 5232 03:47:07,656 --> 03:47:10,593 STANDARD OF CARE AND RANDOMIZED 5233 03:47:10,593 --> 03:47:12,828 TO EXCHANGE WE SAY, LOOK, IF 5234 03:47:12,828 --> 03:47:16,532 IT'S ALMOST THE SAME BETWEEN 40% 5235 03:47:16,532 --> 03:47:19,702 AND 60%, 50/50 YOU'LL BE 5236 03:47:19,702 --> 03:47:20,736 RANDOMIZED TO EXCHANGE OR 5237 03:47:20,736 --> 03:47:22,972 STANDARD OF CARE. 5238 03:47:22,972 --> 03:47:26,442 HOWEVER, IF THE IMBALANCE IS 5239 03:47:26,442 --> 03:47:28,344 SUCH THAT THE IMBALANCE WOULD BE 5240 03:47:28,344 --> 03:47:30,079 WORSE IF RANDOMIZED TO STANDARD 5241 03:47:30,079 --> 03:47:36,185 OF CARE WE USE WHAT WE CALL THAT 5242 03:47:36,185 --> 03:47:38,087 BIASSED COIN DESIGN AND SAY IT 5243 03:47:38,087 --> 03:47:40,789 WILL BE A 75% CHANCE THEY'LL GET 5244 03:47:40,789 --> 03:47:43,392 RED BLOOD CELL CHANGE AND 25% 5245 03:47:43,392 --> 03:47:47,529 THEY'LL GET STANDARD OF CARE 5246 03:47:47,529 --> 03:47:47,763 CHANCE. 5247 03:47:47,763 --> 03:47:49,965 THE IMPORTANT THING IS THAT IT'S 5248 03:47:49,965 --> 03:47:51,400 NEVER DETERMINISTIC. 5249 03:47:51,400 --> 03:47:53,902 THERE'S ALWAYS SOME RANDOMNESS 5250 03:47:53,902 --> 03:47:57,606 IN THIS BUT WE BIAS THE 5251 03:47:57,606 --> 03:47:58,674 RANDOMIZATION IN ORDER TO 5252 03:47:58,674 --> 03:47:59,241 ENHANCE THE BALANCE IN THE 5253 03:47:59,241 --> 03:48:09,351 TRIAL. 5254 03:48:14,023 --> 03:48:15,958 AND WE'RE USING A NUMBER OF 5255 03:48:15,958 --> 03:48:18,494 OUTCOMES IN THIS TRIAL. 5256 03:48:18,494 --> 03:48:20,829 THE FIRST ONE IS THE PRIMARY 5257 03:48:20,829 --> 03:48:22,631 OUTCOME WHICH IS A COUNT OF THE 5258 03:48:22,631 --> 03:48:27,369 NUMBER OF ACUTE HEALTH CARE 5259 03:48:27,369 --> 03:48:27,736 ENCOUNTERS. 5260 03:48:27,736 --> 03:48:30,272 THE SECOND IS ONE THAT'S BECOME 5261 03:48:30,272 --> 03:48:35,811 POPULAR THESE DAYS WHICH IS THE 5262 03:48:35,811 --> 03:48:36,779 ORDERED OUTCOMES WE SAY ON A 5263 03:48:36,779 --> 03:48:41,016 SCALE 1 TO 6 FROM BETTER TO 5264 03:48:41,016 --> 03:48:43,352 WORSE LET'S SEE HOW BAD THINGS 5265 03:48:43,352 --> 03:48:44,720 WERE OVER THE 13 MONTHS OF 5266 03:48:44,720 --> 03:48:47,489 FOLLOW-UP AND PUT YOU ON A SCALE 5267 03:48:47,489 --> 03:48:52,861 1 TO 6 OF NOTHING HAPPENING ALL 5268 03:48:52,861 --> 03:48:54,596 THE WAY TO DEATH. 5269 03:48:54,596 --> 03:48:56,398 YOU CAN THINK HOW LONG ARE YOU 5270 03:48:56,398 --> 03:48:58,133 FREE OF AN ACUTE HEALTH CARE 5271 03:48:58,133 --> 03:49:01,003 ENCOUNTER AND SO THIS IS LIKE 5272 03:49:01,003 --> 03:49:08,377 TIME THREE OF AN EVENT AND THEN 5273 03:49:08,377 --> 03:49:10,779 FINALLY WE LOOK AT THOSE 5274 03:49:10,779 --> 03:49:12,948 LONGITUDINAL OUTCOMES OVER TIME. 5275 03:49:12,948 --> 03:49:14,616 FOR EXAMPLE, HOW DOES PAIN 5276 03:49:14,616 --> 03:49:16,785 CHANGE OVER TIME FROM BASELINE 5277 03:49:16,785 --> 03:49:18,721 ACROSS FOUR MONTHS, EIGHT MONTHS 5278 03:49:18,721 --> 03:49:20,255 AND 12 MONTHS? 5279 03:49:20,255 --> 03:49:21,824 AGAIN, THIS IS A CLINICAL TRIAL 5280 03:49:21,824 --> 03:49:24,793 SO OUR MAJOR GOAL IS TO COMPARE 5281 03:49:24,793 --> 03:49:34,336 THE TWO TREATMENT ARMS. 5282 03:49:34,336 --> 03:49:38,540 THIS IS THE PAINIMATION AND AN 5283 03:49:38,540 --> 03:49:39,274 INNOVATIVE OUTCOME WHERE WE TALK 5284 03:49:39,274 --> 03:49:46,081 ABOUT THE LOCATION OF PAIN, 5285 03:49:46,081 --> 03:49:47,383 INTENSITY AND DURATION. 5286 03:49:47,383 --> 03:49:48,951 OUR GOAL WAS TO SAY WE WANT IT 5287 03:49:48,951 --> 03:49:50,686 USE THESE DATA AS BEST AS 5288 03:49:50,686 --> 03:49:50,986 POSSIBLE. 5289 03:49:50,986 --> 03:49:54,056 SO LET'S DO A SIMULATION STUDY 5290 03:49:54,056 --> 03:49:56,024 TO COMPARE POWER FOR OUR KEY 5291 03:49:56,024 --> 03:49:58,160 OUTCOMES WHICH WE THINK OF AS 5292 03:49:58,160 --> 03:50:00,028 THE COUNT OF HEALTH CARE 5293 03:50:00,028 --> 03:50:01,897 ENCOUNTERS, THE TIME TO THE 5294 03:50:01,897 --> 03:50:03,665 FIRST ACUTE HEALTH CARE 5295 03:50:03,665 --> 03:50:06,502 ENCOUNTER TO THE SIXTH LEVEL 5296 03:50:06,502 --> 03:50:07,870 PRIORITIZED AND I SEE IT'S 5297 03:50:07,870 --> 03:50:11,673 ALREADY 2:00 SO I'LL GO THROUGH 5298 03:50:11,673 --> 03:50:12,508 THIS QUITE QUICKLY. 5299 03:50:12,508 --> 03:50:15,310 WE BASICALLY DID A SIMULATION 5300 03:50:15,310 --> 03:50:17,646 STUDY DOING 10,000 TRIALS 5301 03:50:17,646 --> 03:50:20,616 EFFECTIVELY EACH ONE WITH A 150 5302 03:50:20,616 --> 03:50:24,753 PARTICIPANTS AND SIMULATED DATA 5303 03:50:24,753 --> 03:50:27,856 AS THOUGH THEY HAD HEALTH CARE 5304 03:50:27,856 --> 03:50:29,725 ENCOUNTERS OVER TIME AND MAY OR 5305 03:50:29,725 --> 03:50:32,461 MAY NOT HAVE DIED OR MAY OR MAY 5306 03:50:32,461 --> 03:50:34,029 NOT HAVE HAD COMPLICATIONS. 5307 03:50:34,029 --> 03:50:38,634 I HIGHLIGHT A COUPLE EXAMPLES 5308 03:50:38,634 --> 03:50:41,870 AND THESE ARE SITUATIONS WE 5309 03:50:41,870 --> 03:50:50,879 THOUGHT WERE POSSIBLE WITHIN SCD 5310 03:50:50,879 --> 03:50:53,482 CARRE AND DISTINGUISH BETWEEN 5311 03:50:53,482 --> 03:50:55,184 3.68 HEALTH CARE ENCOUNTERS IN 5312 03:50:55,184 --> 03:50:57,920 ONE ARM COMPARED TO A 26% 5313 03:50:57,920 --> 03:51:00,823 REDUCTION WHICH IS 2.72 HEALTH 5314 03:51:00,823 --> 03:51:02,057 CARE ENCOUNTERS. 5315 03:51:02,057 --> 03:51:06,862 THE QUESTION IS, HOW DOES THE 5316 03:51:06,862 --> 03:51:08,764 POWER WORK FOR DETECT THE 5317 03:51:08,764 --> 03:51:11,366 CHANGES IF THIS WERE THE 5318 03:51:11,366 --> 03:51:11,633 SITUATION? 5319 03:51:11,633 --> 03:51:12,801 THE DIFFERENCE BETWEEN SCENARIO 5320 03:51:12,801 --> 03:51:16,371 2 AND 3 ARE WHAT IF COMPLICATION 5321 03:51:16,371 --> 03:51:21,276 IN THE RANGE OF 10% TO 8% PER 5322 03:51:21,276 --> 03:51:22,878 HEALTH CARE ENCOUNTER OR IF 5323 03:51:22,878 --> 03:51:30,919 THERE ARE A WHOPPING 37%. 5324 03:51:30,919 --> 03:51:33,055 YOU'LL SEE IN THE PICTURES THE 5325 03:51:33,055 --> 03:51:36,158 COUNT IS ACTUALLY QUITE 5326 03:51:36,158 --> 03:51:40,429 EFFECTIVE IN TERMS OF 5327 03:51:40,429 --> 03:51:40,996 DISTINGUISHING BETWEEN ONE 5328 03:51:40,996 --> 03:51:41,563 SCENARIO AND ANOTHER. 5329 03:51:41,563 --> 03:51:46,835 AT THE RIGHT THE PRIORITIZED IN 5330 03:51:46,835 --> 03:51:51,740 OTHER WORDS GOING FROM A 1 TO 6 5331 03:51:51,740 --> 03:51:55,110 DOESN'T DISTINGUISH MUCH IF SOME 5332 03:51:55,110 --> 03:51:57,579 HAVE ENCOUNTERS OR 1 OR 0 5333 03:51:57,579 --> 03:51:58,814 COMPLICATIONS WHERE IT DOES 5334 03:51:58,814 --> 03:52:00,182 DISTINGUISH THE MORE SPREAD 5335 03:52:00,182 --> 03:52:01,116 THERE IS. 5336 03:52:01,116 --> 03:52:03,385 IF THERE'S AN ORDERED OUTCOME 5337 03:52:03,385 --> 03:52:05,487 WHERE YOU HAVE PEOPLE WITH MILD 5338 03:52:05,487 --> 03:52:06,688 OUTCOMES AS WELL AS SEVERE 5339 03:52:06,688 --> 03:52:07,222 OUTCOMES. 5340 03:52:07,222 --> 03:52:10,392 I HAVE TWO MORE SLIDES. 5341 03:52:10,392 --> 03:52:14,596 THAT'S BASICALLY WHAT WE 5342 03:52:14,596 --> 03:52:16,598 CONCLUDED WAS THAT TO THE COUNT 5343 03:52:16,598 --> 03:52:18,901 OUTCOME HAD THE HIGHEST 5344 03:52:18,901 --> 03:52:20,669 STATISTICAL POWER THE COUNT OF 5345 03:52:20,669 --> 03:52:22,404 ACUTE HEALTH CARE ENCOUNTERS. 5346 03:52:22,404 --> 03:52:24,740 I WAS PERSONALLY SURPRISED THAT 5347 03:52:24,740 --> 03:52:28,443 TIME TO EVENT DID NOT EXCEED 90% 5348 03:52:28,443 --> 03:52:31,213 POIR IN ANY OF OUR SCENARIOS AND 5349 03:52:31,213 --> 03:52:33,215 THAT AND ORDERED RANK OUTCOME 5350 03:52:33,215 --> 03:52:34,483 WHICH HAS BECOME POPULAR WORKS 5351 03:52:34,483 --> 03:52:36,618 WELL IF YOU HAVE A WIDE 5352 03:52:36,618 --> 03:52:38,921 DISTRIBUTION OF DATA BUT DID NOT 5353 03:52:38,921 --> 03:52:42,124 ACTUALLY DO SO WELL IF PEOPLE 5354 03:52:42,124 --> 03:52:45,894 ARE CLUSTERED ON ONE END OR THE 5355 03:52:45,894 --> 03:52:48,597 OTHER. 5356 03:52:48,597 --> 03:52:52,267 WE RECOGNIZE THE GENERALIZE ARE 5357 03:52:52,267 --> 03:52:55,571 BASED ON THE SITUATION. 5358 03:52:55,571 --> 03:53:01,376 I CONCLUDE SCDCARRE IS THE BEST 5359 03:53:01,376 --> 03:53:03,412 OPTION FOR HIGH RISK PATIENTS 5360 03:53:03,412 --> 03:53:08,984 WITH SICKLE CELL DISEASE AND 5361 03:53:08,984 --> 03:53:10,052 BOTH INTERVENTION STRATEGIES 5362 03:53:10,052 --> 03:53:12,788 CONSISTENT WITH STANDARD OF CARE 5363 03:53:12,788 --> 03:53:14,790 OR STANDARD OF CARE PLUS RED 5364 03:53:14,790 --> 03:53:15,791 BLOOD CELL EXCHANGE. 5365 03:53:15,791 --> 03:53:16,825 OUR GOAL AS WE IMPLEMENT THE 5366 03:53:16,825 --> 03:53:18,927 TRIAL IS TO GET TO THE MOST OUT 5367 03:53:18,927 --> 03:53:25,467 OF THE DATA WE HAVE IN THE 5368 03:53:25,467 --> 03:53:27,269 TRIAL. 5369 03:53:27,269 --> 03:53:29,571 AND FOCUS ON MAKING SURE OUR TWO 5370 03:53:29,571 --> 03:53:31,106 INTERVENTION GROUPS ARE AS 5371 03:53:31,106 --> 03:53:32,774 COMPARABLE AS POSSIBLE AND WE'RE 5372 03:53:32,774 --> 03:53:36,812 USING A COVARIATE ADAPTIVE 5373 03:53:36,812 --> 03:53:39,481 RANDOMIZATION EXTREME TO DO THAT 5374 03:53:39,481 --> 03:53:41,817 AND TRYING TO IDENTIFY CLINICAL 5375 03:53:41,817 --> 03:53:44,186 AND PATIENT-CENTERED OUTCOMES 5376 03:53:44,186 --> 03:53:45,921 THAT ARE IMPORTANT TO 5377 03:53:45,921 --> 03:53:47,889 PARTICIPANTS BUT ALSO HAVE A 5378 03:53:47,889 --> 03:53:50,258 VARIETY OF ANALYTIC APPROACHES 5379 03:53:50,258 --> 03:53:52,027 AND FOCUSSING ON THOSE THAT HAVE 5380 03:53:52,027 --> 03:53:54,730 GOOD STATISTICAL POWER SO WE'RE 5381 03:53:54,730 --> 03:53:58,200 IN A POSITION TO DETECT 5382 03:53:58,200 --> 03:53:58,834 CLINICALLY MEANINGFUL TREATMENT 5383 03:53:58,834 --> 03:54:00,769 DIFFERENCES. 5384 03:54:00,769 --> 03:54:05,941 THANK YOU. 5385 03:54:05,941 --> 03:54:07,476 >> THANK YOU, MARIA? 5386 03:54:07,476 --> 03:54:17,285 ANY CALLING QUESTIONS? 5387 03:54:17,285 --> 03:54:22,658 >> WALLY SMITH FROM RICHMOND. 5388 03:54:22,658 --> 03:54:26,828 SO I THINK OF EVENTS AS 5389 03:54:26,828 --> 03:54:29,398 HURRICANES AND THINK OF SUB 5390 03:54:29,398 --> 03:54:31,833 CLINICAL PAIN CRISES AT HOME AND 5391 03:54:31,833 --> 03:54:36,505 OTHER PAIN AS OTHER EVENTS LIKE 5392 03:54:36,505 --> 03:54:41,877 TORNADOS AND PREVAILING WINDS. 5393 03:54:41,877 --> 03:54:50,619 SO THE STACK INTRIGUES ME BUT 5394 03:54:50,619 --> 03:54:52,320 NOT SURPRISED HURRICANES CAUSE 5395 03:54:52,320 --> 03:54:53,822 DEATH AND CURIOUS ABOUT THE 5396 03:54:53,822 --> 03:54:56,792 STACK AND THE METAPHOR I GOT 5397 03:54:56,792 --> 03:54:57,392 THROUGH TALKING ABOUT THE 5398 03:54:57,392 --> 03:54:59,494 ORDERED RANKING AND TRY TO PUT 5399 03:54:59,494 --> 03:55:02,330 SOME WEIGHT ON THOSE. 5400 03:55:02,330 --> 03:55:05,534 >> YEAH, SO I HEAR WHAT YOU'RE 5401 03:55:05,534 --> 03:55:05,901 SAYING. 5402 03:55:05,901 --> 03:55:07,302 WHEN YOU JUST COUNT HEALTH CARE 5403 03:55:07,302 --> 03:55:09,638 ENCOUNTERS IT DOESN'T FEEL LIKE 5404 03:55:09,638 --> 03:55:13,608 THEY SHOULD ALL HAVE EQUAL 5405 03:55:13,608 --> 03:55:14,409 WEIGHT, RIGHT. 5406 03:55:14,409 --> 03:55:17,279 SO WORSE LIKE WHEN WE TRY TO 5407 03:55:17,279 --> 03:55:20,282 DEFINE THOSE AS THE END ORGAN 5408 03:55:20,282 --> 03:55:21,950 COMPLICATIONS IT MEANS SOMETHING 5409 03:55:21,950 --> 03:55:24,319 WORSE THAN JUST THOUGH WE KNOW 5410 03:55:24,319 --> 03:55:25,821 THE VASO OCCLUSIVE CRISIS ARE 5411 03:55:25,821 --> 03:55:28,590 VERY BAD, WE THOUGHT THOSE MAYBE 5412 03:55:28,590 --> 03:55:31,426 ARE LIKE THE HURRICANES THAT MAY 5413 03:55:31,426 --> 03:55:32,394 LEAD TO DEATH. 5414 03:55:32,394 --> 03:55:35,263 THAT WAS OUR ATTEMPT AT TRYING 5415 03:55:35,263 --> 03:55:36,565 TO SAY NOT ALL HEALTH CARE 5416 03:55:36,565 --> 03:55:43,505 ENCOUNTERS ARE EQUALLY BAD AND 5417 03:55:43,505 --> 03:55:47,275 TRYING TO SEPARATE OUT. 5418 03:55:47,275 --> 03:55:49,311 THE QUESTION IS IS THERE ENOUGH 5419 03:55:49,311 --> 03:55:50,746 DIFFERENTIATION OF PARTICIPANTS 5420 03:55:50,746 --> 03:55:52,280 IN A TRIAL LIKE THIS TO SEE THAT 5421 03:55:52,280 --> 03:55:54,516 AND ARE WE FOLLOWING THEM LONG 5422 03:55:54,516 --> 03:55:55,383 ENOUGH SO THAT AGAIN WE ARE 5423 03:55:55,383 --> 03:55:58,420 SEEING THEM ALL THE WAY THROUGH 5424 03:55:58,420 --> 03:56:08,964 TO THESE UNFORTUNATE HURRICANES. 5425 03:56:10,065 --> 03:56:12,801 WE'LL HAVE TO PUT THAT IN. 5426 03:56:12,801 --> 03:56:14,503 >> THANK YOU FOR A WONDERFUL 5427 03:56:14,503 --> 03:56:14,770 TALK. 5428 03:56:14,770 --> 03:56:18,807 WE'RE GOING TO TAKE A SHORT 5429 03:56:18,807 --> 03:56:20,675 BREAK UNTIL 2:15. 5430 03:56:20,675 --> 03:56:23,545 AND PLEASE COME IN HERE PROMPTLY 5431 03:56:23,545 --> 03:56:25,714 AT 2:15 OR EARLIER. 5432 03:56:25,714 --> 03:56:28,464 WE HAVE SYMPOSIUM 2 GENE THERAPY 5433 03:56:28,464 --> 03:56:30,466 TO BE GENE THERAPY CLINICAL 5434 03:56:30,466 --> 03:56:30,977 IMPLEMENTATIONS. 5435 03:56:30,977 --> 03:56:31,277 PATIENT AND PROVIDER PERSPECTIVE. 5436 03:56:31,277 --> 03:56:35,381 TALK ABOUT GENE THERAPY FOR 5437 03:56:35,381 --> 03:56:38,550 SICKLE CELL DISEASE, WHO, HOW, 5438 03:56:38,550 --> 03:56:40,363 WHERE AND WHEN. 5439 03:56:40,363 --> 03:56:46,169 CHAIRS ARE DR. FITZHUGH AND 5440 03:56:46,169 --> 03:56:47,871 DR. STROUSE FOR THIS TALK. 5441 03:56:47,871 --> 03:56:48,572 >> ALL RIGHT. 5442 03:56:48,572 --> 03:56:51,141 THANK YOU. 5443 03:56:51,141 --> 03:56:55,045 SO I WANT TO THANK THE NHLBI FOR 5444 03:56:55,045 --> 03:57:00,917 INVITING US TO DO THIS 5445 03:57:00,917 --> 03:57:11,094 SYMPOSIUM. 5446 03:57:13,764 --> 03:57:19,002 OUR SYMPOSIUM IS GENE THERAPY, 5447 03:57:19,002 --> 03:57:19,936 CLINICAL IMPLEMENTATION. 5448 03:57:19,936 --> 03:57:22,205 THIS IS THE SICKLE CELL ADULT 5449 03:57:22,205 --> 03:57:22,639 PROVIDER SYMPOSIUM. 5450 03:57:22,639 --> 03:57:27,144 I WANT TO START WITH THE MISSION 5451 03:57:27,144 --> 03:57:29,212 TO ESTABLISH AND SUPPORT AN 5452 03:57:29,212 --> 03:57:30,247 INTERACTIVE NETWORK FOR HEALTH 5453 03:57:30,247 --> 03:57:31,181 CARE PROVIDERS AND INVESTIGATORS 5454 03:57:31,181 --> 03:57:35,485 WHO SERVE ADULTS WITH SICKLE 5455 03:57:35,485 --> 03:57:38,121 CELL DISEASE AND WELCOME 5456 03:57:38,121 --> 03:57:41,491 PARTICIPATION FOR ANY PROVIDER 5457 03:57:41,491 --> 03:57:43,360 WITH AN INTEREST IN SICKLE CELL 5458 03:57:43,360 --> 03:57:46,563 DISEASE AND FAMILIES MEMBERS 5459 03:57:46,563 --> 03:57:47,931 LIVING WITH SICKLE CELL DISEASE. 5460 03:57:47,931 --> 03:57:53,470 SO THE GOALS ARE TO ESTABLISH 5461 03:57:53,470 --> 03:57:58,575 COMMUNICATION AND SUPPORT AMONG 5462 03:57:58,575 --> 03:58:04,514 ADULT SICKLE CELL DISEASE 5463 03:58:04,514 --> 03:58:07,184 PROVIDERS AND HAVE A WHAT'S APP 5464 03:58:07,184 --> 03:58:11,254 GROUP AND TO DEVELOP AND 5465 03:58:11,254 --> 03:58:13,190 DISSEMINATE ADULT SICKLE CELL 5466 03:58:13,190 --> 03:58:18,161 DISEASE INFORMATION AND ATTRACT 5467 03:58:18,161 --> 03:58:26,503 AND FOSTER CAREERS AND SCAPN WAS 5468 03:58:26,503 --> 03:58:29,472 INCORPORATED IN 2003 AND WE HAVE 5469 03:58:29,472 --> 03:58:31,508 ASSIST AN FOR CAREER DEVELOPMENT 5470 03:58:31,508 --> 03:58:35,478 AND HAVE THE WHAT'S APP GROUP 5471 03:58:35,478 --> 03:58:37,113 WHICH REQUIRES AN ADMINISTRATOR 5472 03:58:37,113 --> 03:58:41,284 APPROVAL AND LIMITED TO 5473 03:58:41,284 --> 03:58:42,085 PROVIDERS WITH SICKLE CELL 5474 03:58:42,085 --> 03:58:42,452 DISEASE HELP. 5475 03:58:42,452 --> 03:58:45,088 TODAY WE ARE GOING HAVE TWO 5476 03:58:45,088 --> 03:58:49,726 CASES OF PEOPLE THAT ARE 5477 03:58:49,726 --> 03:58:50,694 REQUESTING THERAPY. 5478 03:58:50,694 --> 03:58:56,533 THE FIRST CASE THE DISCUSSANTS 5479 03:58:56,533 --> 03:59:05,175 WILL BE SOPHIE LANZKRON AND RABI 5480 03:59:05,175 --> 03:59:07,944 HANNA AND WE'LL ANSWER QUESTIONS 5481 03:59:07,944 --> 03:59:13,250 ABOUT THE CASES AND DISCUSSION 5482 03:59:13,250 --> 03:59:16,319 AND JOINED WITH AN A PERSON WITH 5483 03:59:16,319 --> 03:59:17,020 SICKLE CELL DISEASE WHOSE UNDER 5484 03:59:17,020 --> 03:59:19,356 GONE CURATIVE THERAPY AND 5485 03:59:19,356 --> 03:59:25,862 JOINING US JULIE KANTER WILL 5486 03:59:25,862 --> 03:59:26,730 PRESENT ON GENE THERAPY 5487 03:59:26,730 --> 03:59:34,004 PROGRAMS. 5488 03:59:34,004 --> 03:59:35,672 WITH THAT I'LL PRESENT THE FIRST 5489 03:59:35,672 --> 03:59:38,141 CASE AND THEN WE'RE GOING TO GO 5490 03:59:38,141 --> 03:59:39,109 BACK AND FORTH WITH THE 5491 03:59:39,109 --> 03:59:39,709 QUESTIONS BETWEEN OUR TWO 5492 03:59:39,709 --> 03:59:45,148 DISCUSS IN THE JA -- DISCUSSANTS 5493 03:59:45,148 --> 03:59:47,017 AND A 26-YEAR-OLD WOMAN WITH 5494 03:59:47,017 --> 03:59:49,719 HBSS AND ISCHEMIC STROKE AND HAS 5495 03:59:49,719 --> 03:59:53,490 HAD DIFFICULTY MAINTAINING 5496 03:59:53,490 --> 03:59:55,191 REGULAR RED BLOOD CELL 5497 03:59:55,191 --> 03:59:56,326 TRANSFUSIONS SECONDARY TO 5498 03:59:56,326 --> 03:59:58,328 TRANSPORTATION AND OTHER 5499 03:59:58,328 --> 03:59:58,728 BARRIERS. 5500 03:59:58,728 --> 04:00:06,903 SHE HAD A RECURRENT STROKE AFTER 5501 04:00:06,903 --> 04:00:08,772 THREE MONTH SYMPTOM IN 5502 04:00:08,772 --> 04:00:09,072 TRANSFUSION. 5503 04:00:09,072 --> 04:00:12,309 SHE'S BEEN ON INTERMITTENT 5504 04:00:12,309 --> 04:00:16,513 TRANSFUSION AND CONTINUOUS HI 5505 04:00:16,513 --> 04:00:17,714 HYDROXYUREA AND HAD AN INITIAL 5506 04:00:17,714 --> 04:00:23,486 STROKE IN 2015 AND ANOTHER IN 5507 04:00:23,486 --> 04:00:27,023 2023 WITH A MILD RIGHT HEMI 5508 04:00:27,023 --> 04:00:31,928 PARESIS AND HOSPITALIZED ON 5509 04:00:31,928 --> 04:00:36,566 AVERAGE ONCE A YEAR WITH VASO 5510 04:00:36,566 --> 04:00:38,401 OCCLUSIVE ADVOCATES AND HAD 5511 04:00:38,401 --> 04:00:41,905 ACUTE CHEST SYNDROME TWICE AND 5512 04:00:41,905 --> 04:00:46,977 ADMISSION BUT TRANSFUSED AND HAS 5513 04:00:46,977 --> 04:00:50,013 SIGNIFICANT TRANSFUSIONAL IRON 5514 04:00:50,013 --> 04:00:54,684 OVERLOAD AND SICKLE CELL 5515 04:00:54,684 --> 04:00:55,385 RETINOP 5516 04:00:55,385 --> 04:00:55,685 RETINOPATHY. 5517 04:00:55,685 --> 04:01:02,225 SHE HAS NORMAL CARDIAC FUNCTION 5518 04:01:02,225 --> 04:01:08,498 AND ATRIAL SHUNTING AND HAD 5519 04:01:08,498 --> 04:01:19,009 ARTERY OCCLUSION AND MOYAMOYA 5520 04:01:21,244 --> 04:01:24,514 AND HAD THE INDICATED DRY WEIGHT 5521 04:01:24,514 --> 04:01:28,518 LIVER AND HAD AN ALT IN THE 5522 04:01:28,518 --> 04:01:30,053 UPPER 5523 04:01:30,053 --> 04:01:40,530 UPPER 40s AND HAS NO MICR 5524 04:01:54,077 --> 04:01:54,444 MICROALBUMINURIA. 5525 04:01:54,444 --> 04:01:56,546 I'LL GIVE THE FIRST DISCUSSION 5526 04:01:56,546 --> 04:02:01,084 QUESTION THE EFFICACY OF GENE 5527 04:02:01,084 --> 04:02:04,120 THERAPY VERSUS TRANSPLANTATION 5528 04:02:04,120 --> 04:02:07,857 FOR PEOPLE WITH SICKLE CELL 5529 04:02:07,857 --> 04:02:18,268 DISEASE IN CNS DISEASE. 5530 04:02:19,569 --> 04:02:29,746 DR. LANZKRON. 5531 04:03:04,547 --> 04:03:05,982 >> WE DON'T HAVE A LOT OF DATA. 5532 04:03:05,982 --> 04:03:08,351 THIS IS A 26-YEAR-OLD ONE OF THE 5533 04:03:08,351 --> 04:03:11,054 KEY THINGS MENTIONED WAS HER 5534 04:03:11,054 --> 04:03:15,058 COGNITIVE DISFUNCTION AND 5535 04:03:15,058 --> 04:03:16,960 NON-ADHERENCE TO HER THERAPY 5536 04:03:16,960 --> 04:03:18,461 RELATED TO HER COGNITIVE 5537 04:03:18,461 --> 04:03:19,629 DYSFUNCTION. 5538 04:03:19,629 --> 04:03:24,501 WE KNOW AND HEARD THIS MORNING 5539 04:03:24,501 --> 04:03:27,437 HEMATOPOIETIC STEM CELL ENHANCES 5540 04:03:27,437 --> 04:03:30,373 BLOOD FLOW AND WE LOOKED AT 5541 04:03:30,373 --> 04:03:32,075 CEREBRAL FLOOD FLOW AND THE 5542 04:03:32,075 --> 04:03:35,278 META-ANALYSIS FOR ALL THE TRIALS 5543 04:03:35,278 --> 04:03:40,884 IMPROVE AFTER HEMATOPOIETIC STEM 5544 04:03:40,884 --> 04:03:42,485 CELL AND KNOW FROM THE FRENCH 5545 04:03:42,485 --> 04:03:44,487 THE RISK OF RECURRENT STROKE IS 5546 04:03:44,487 --> 04:03:55,031 ABOUT 5.5% OR SO AFTER A HEE 5547 04:03:56,566 --> 04:03:56,733 HEEMENT -- 5548 04:04:00,570 --> 04:04:03,907 HEMATOPOIETIC EVENT AND WE NEED 5549 04:04:03,907 --> 04:04:05,708 SOME FORM OF CURATIVE THERAPY 5550 04:04:05,708 --> 04:04:06,809 SINCE THE PERSON IS 26. 5551 04:04:06,809 --> 04:04:09,946 THE KEY IS THEY NEED A COMMUNITY 5552 04:04:09,946 --> 04:04:15,718 HEALTH WORKER 5553 04:04:15,718 --> 04:04:16,753 NAVIGATE THE HEALTH CARE SYSTEM 5554 04:04:16,753 --> 04:04:18,621 BECAUSE THE COGNITIVE DEFICITS 5555 04:04:18,621 --> 04:04:22,225 ARE CAUSING SOME OF THE 5556 04:04:22,225 --> 04:04:22,525 CHALLENGES. 5557 04:04:22,525 --> 04:04:27,864 THE QUESTION IS HEMATOPOIETIC 5558 04:04:27,864 --> 04:04:30,733 STEM CELL VERSUS GENE THERAPY. 5559 04:04:30,733 --> 04:04:33,670 WE WANT IT TO BE PROTECTIVE BUT 5560 04:04:33,670 --> 04:04:35,271 I THINK THERE ARE ONGOING 5561 04:04:35,271 --> 04:04:35,538 CONCERNS. 5562 04:04:35,538 --> 04:04:39,275 WE DON'T KNOW IT'S NOT AS IF 5563 04:04:39,275 --> 04:04:49,986 THEY STOP HEMOLIES YZE -- 5564 04:04:55,692 --> 04:05:04,534 HEMOLYZING AND THE GRAFMENT OF 5565 04:05:04,534 --> 04:05:14,811 THEIR PLATELETS. 5566 04:05:18,681 --> 04:05:21,050 >> WE HAVE LITTLE KNOWLEDGE FROM 5567 04:05:21,050 --> 04:05:22,485 THE GENE THERAPY PERSPECTIVE. 5568 04:05:22,485 --> 04:05:24,120 MANY OF THE CLINICAL TRIAL YOU 5569 04:05:24,120 --> 04:05:27,457 HAVE SEEN ESPECIALLY IN GENE 5570 04:05:27,457 --> 04:05:29,092 EDITING THE PATIENT WHO HAVE 5571 04:05:29,092 --> 04:05:30,727 EVIDENCE OF STROKE WERE EXCLUDED 5572 04:05:30,727 --> 04:05:33,062 FROM THAT SO WE TRULY DO NOT 5573 04:05:33,062 --> 04:05:33,663 HAVE EVIDENCE. 5574 04:05:33,663 --> 04:05:37,300 THE ONLY DATA WE HAVE IS IN THE 5575 04:05:37,300 --> 04:05:44,507 EARLIER PHASES OF THIS GENE 5576 04:05:44,507 --> 04:05:44,774 ADDITION. 5577 04:05:44,774 --> 04:05:47,010 THEY HAD FIVE PATIENTS OF 5578 04:05:47,010 --> 04:05:49,812 EVIDENCE OF REMOTE STROKE 5579 04:05:49,812 --> 04:05:52,515 INCLUDED IN THAT PATIENT 5580 04:05:52,515 --> 04:05:53,583 POPULATION AMONG THEIR 40 5581 04:05:53,583 --> 04:05:55,118 PATIENTS THEY PUBLISHED ON BUT 5582 04:05:55,118 --> 04:05:56,753 WE DON'T REALLY HAVE ANY 5583 04:05:56,753 --> 04:05:59,789 SPECIFIC DATA IN TERMS OF THE 5584 04:05:59,789 --> 04:06:02,425 NEUROLOGICAL OUTCOME OR 5585 04:06:02,425 --> 04:06:04,093 REOCCURRENCE OR NOT IN THE GENE 5586 04:06:04,093 --> 04:06:04,327 THERAPY. 5587 04:06:04,327 --> 04:06:07,330 ON THE OTHER HAND AS YOU HEARD 5588 04:06:07,330 --> 04:06:09,365 FROM MANY PREVIOUS STUDIES MORE 5589 04:06:09,365 --> 04:06:13,036 FROM WHAT I THINK ARE THE MOST 5590 04:06:13,036 --> 04:06:18,675 PROSPECT OF DATA WERE THE 5591 04:06:18,675 --> 04:06:22,845 EUROPEAN AND GROUP SHOWED 5592 04:06:22,845 --> 04:06:27,283 IMPROVEMENT IN THE CNS VASCULAR 5593 04:06:27,283 --> 04:06:35,892 ONOPATHY AND THE MOST RECENT 5594 04:06:35,892 --> 04:06:37,794 1507 THEY HAD PATIENT WITH 5595 04:06:37,794 --> 04:06:39,896 EVIDENCE OF ADDING MORE STROKE 5596 04:06:39,896 --> 04:06:42,165 THAT WAS INCLUDED OR SILENT 5597 04:06:42,165 --> 04:06:44,400 STROKE WHETHER CLINICAL OR SOME 5598 04:06:44,400 --> 04:06:48,538 STROKE INCLUDED ON IT. 5599 04:06:48,538 --> 04:06:51,607 AND AS WAS PUBLISHED FROM THE 5600 04:06:51,607 --> 04:06:53,509 VANDERBILT CONSORTIUM ALMOST 52% 5601 04:06:53,509 --> 04:06:57,680 OF PATIENTS WERE ENROLLED ON 5602 04:06:57,680 --> 04:07:00,817 THEIR CLINICAL TRIAL THEY HAD 5603 04:07:00,817 --> 04:07:01,417 EVIDENCE OF CNS DISEASE AND 5604 04:07:01,417 --> 04:07:03,286 THERE WAS NO REOCCURRENCE OF THE 5605 04:07:03,286 --> 04:07:06,155 STROKE IN THE PATIENT. 5606 04:07:06,155 --> 04:07:11,661 SO FROM A SAFETY OF BONE MARROW 5607 04:07:11,661 --> 04:07:13,062 TRANSPLANT I FEEL COMFORTABLE TO 5608 04:07:13,062 --> 04:07:18,801 OFFER IT FOR A PATIENT IF THEY 5609 04:07:18,801 --> 04:07:19,736 REALLY HAVE WHAT YOU HEARD OF 5610 04:07:19,736 --> 04:07:20,870 THE IMPORTANCE OF BEING PREPARED 5611 04:07:20,870 --> 04:07:24,140 FOR THE TRANSPLANT AND THIS 5612 04:07:24,140 --> 04:07:25,775 PATIENT I WOULD HAVE CONCERNS 5613 04:07:25,775 --> 04:07:30,613 ABOUT IT BUT AS A PHYSICIAN OR 5614 04:07:30,613 --> 04:07:32,148 TRANSPLANTER I WOULD NOT OFFER 5615 04:07:32,148 --> 04:07:33,716 GENE THERAPY FOR THIS PATIENT. 5616 04:07:33,716 --> 04:07:39,922 I WOULD DISCUSS THEIR ELIGI 5617 04:07:39,922 --> 04:07:42,525 ELIGIBILITY OF THE PROCESS OR 5618 04:07:42,525 --> 04:07:47,663 HAPLO TRANSPLANT AND SEE IF THEY 5619 04:07:47,663 --> 04:07:55,905 WOULD UNDERSTAND AND SOMEONE I 5620 04:07:55,905 --> 04:07:56,506 CONSIDER FOR ALLO GENIC 5621 04:07:56,506 --> 04:08:05,681 TRANSPLANT. 5622 04:08:05,681 --> 04:08:11,654 >> THERE'S RISK AND BENEFITS OF 5623 04:08:11,654 --> 04:08:15,191 THE HAPLO. 5624 04:08:15,191 --> 04:08:17,393 >> THAT'S A VERY GOOD QUESTION. 5625 04:08:17,393 --> 04:08:19,562 SO THE QUESTION TO REPEAT IS 5626 04:08:19,562 --> 04:08:20,696 RISK AND BENEFIT OF THE 5627 04:08:20,696 --> 04:08:22,165 CONDITIONAL THERAPY. 5628 04:08:22,165 --> 04:08:27,637 SO THIS PATIENT REVIEWING THE 5629 04:08:27,637 --> 04:08:29,672 SUMMARY SLIDE THAT WAS YOU'LL 5630 04:08:29,672 --> 04:08:32,475 REMEMBER EVIDENCE OF HIGH IRON 5631 04:08:32,475 --> 04:08:35,011 OVERLOAD AS EVIDENCED BY THE 5632 04:08:35,011 --> 04:08:44,487 IRON IN TERMS OF WAS 11.7 PER 5633 04:08:44,487 --> 04:08:54,997 DESI -- DECILITER AND IT'S A 5634 04:08:58,501 --> 04:09:01,838 COMPLICATION IN HEMOGLOBINOPATHY 5635 04:09:01,838 --> 04:09:03,206 AND IN OTHER ON INSTRUCTIVE 5636 04:09:03,206 --> 04:09:03,473 SYNDROME. 5637 04:09:03,473 --> 04:09:05,908 I WOULD LIKE TO KNOW IF YOU HAVE 5638 04:09:05,908 --> 04:09:08,778 DATA BECAUSE YOU MEASURE THE 5639 04:09:08,778 --> 04:09:14,050 IRON AND WOULD LIKE TO KNOW IF 5640 04:09:14,050 --> 04:09:15,184 THERE'S EVIDENCE IN THE LIVER 5641 04:09:15,184 --> 04:09:16,486 BECAUSE THAT TO ME IS MORE 5642 04:09:16,486 --> 04:09:21,157 IMPORTANT THAN THE PERCENTAGE OF 5643 04:09:21,157 --> 04:09:23,226 HOW MUCH IRON THERE IS AND YOU 5644 04:09:23,226 --> 04:09:25,528 COULD GET THAT DATA FROM THE MRI 5645 04:09:25,528 --> 04:09:29,098 OF THE LIVER TO SEE EVIDENCE OF 5646 04:09:29,098 --> 04:09:30,700 FIBROSIS OR OCCASIONALLY SEE A 5647 04:09:30,700 --> 04:09:34,136 SCAN OR ANOTHER METHOD TO DETECT 5648 04:09:34,136 --> 04:09:36,105 IF THERE'S FIBROSIS BECAUSE THAT 5649 04:09:36,105 --> 04:09:38,875 WOULD MAKE ME DEFINITELY PUSH 5650 04:09:38,875 --> 04:09:41,644 TOWARDS REDUCE INTENSITY IN 5651 04:09:41,644 --> 04:09:44,213 CONDITIONAL REGIMENT AND WANT TO 5652 04:09:44,213 --> 04:09:47,049 HIGHLIGHT THE CR TN1507 SHOULD 5653 04:09:47,049 --> 04:09:50,586 LOW MORTALITY EVEN FOR MANY 5654 04:09:50,586 --> 04:09:55,291 PATIENT WHO HAVE HIGH 5655 04:09:55,291 --> 04:09:57,260 COMORBIDITY AND THAT WOULD BE 5656 04:09:57,260 --> 04:10:01,531 THE REGIMENT I WOULD CHOOSE FOR 5657 04:10:01,531 --> 04:10:02,798 THE PATIENT AND WHENEVER WE USE 5658 04:10:02,798 --> 04:10:07,370 REDUCE INTENSITY WE GET 5659 04:10:07,370 --> 04:10:12,542 CONCERNED ABOUT EITHER GRAPH 5660 04:10:12,542 --> 04:10:16,812 FAILURE AND WE COULD MITIGATE 5661 04:10:16,812 --> 04:10:18,014 THAT RISK. 5662 04:10:18,014 --> 04:10:20,483 THE SECOND RISK IS THE MIXED 5663 04:10:20,483 --> 04:10:22,018 CHIMERISM IN ADULT. 5664 04:10:22,018 --> 04:10:25,855 WE'RE SEEING LOWER RISK OF MIXED 5665 04:10:25,855 --> 04:10:29,358 CRIMER SIX USING THE CONDITIONED 5666 04:10:29,358 --> 04:10:31,527 THERAPY VERSUS THE REGIMENT AND 5667 04:10:31,527 --> 04:10:35,698 I WOULD RECOMMEND TO REDUCE 5668 04:10:35,698 --> 04:10:38,968 INTENSITY CONDITIONING THROUGH 5669 04:10:38,968 --> 04:10:40,970 THERAPY AND TBR AND IF YOU HAVE 5670 04:10:40,970 --> 04:10:42,204 ACCESS TO IT. 5671 04:10:42,204 --> 04:10:44,907 IF NOT YOU THEN INCREASE THE TBI 5672 04:10:44,907 --> 04:10:48,544 TO 400 PLUS THE ATG WITH THE 5673 04:10:48,544 --> 04:10:59,021 POST TRANSPLANT SITE AS THE 5674 04:11:01,324 --> 04:11:08,064 PROPHYLACTIC RENIMENT. 5675 04:11:08,064 --> 04:11:11,334 -- REGIMENT. 5676 04:11:11,334 --> 04:11:13,803 >> WITH THE UNDERLYING 5677 04:11:13,803 --> 04:11:15,471 TRANSPLANT IS WORRISOME. 5678 04:11:15,471 --> 04:11:17,573 I THINK HER IRON OVERLOAD SAY 5679 04:11:17,573 --> 04:11:18,274 BIG CONCERN. 5680 04:11:18,274 --> 04:11:20,309 THERE'S NO DATA I COULD FIND IN 5681 04:11:20,309 --> 04:11:22,144 SICKLE CELL DISEASE BUT LOTS OF 5682 04:11:22,144 --> 04:11:23,879 DATA THAT PEOPLE WITH IRON 5683 04:11:23,879 --> 04:11:27,783 OVERLOAD HAVE REDUCED OVER ALL 5684 04:11:27,783 --> 04:11:28,985 SURVIVAL AND IN THE POPULATION 5685 04:11:28,985 --> 04:11:31,187 HAVE MORE NON-RELAPSE RELATED 5686 04:11:31,187 --> 04:11:31,687 MORTALITY. 5687 04:11:31,687 --> 04:11:34,991 I THINK IT INCREASES THE RISK. 5688 04:11:34,991 --> 04:11:36,525 AGAIN, SHE'S ONLY 26 YEARS OLD 5689 04:11:36,525 --> 04:11:40,496 AND TRYING TO FIGURE OUT HOW TO 5690 04:11:40,496 --> 04:11:42,131 NAVIGATE IMPROVING HER IRON 5691 04:11:42,131 --> 04:11:44,066 SITUATION IN ORDER TO GO TO 5692 04:11:44,066 --> 04:11:44,867 TRANSPLANT IS KEY. 5693 04:11:44,867 --> 04:11:48,537 SHE ALREADY HAS AMOYAMOYA AND 5694 04:11:48,537 --> 04:11:49,505 NUMEROUS COMPLICATIONS. 5695 04:11:49,505 --> 04:11:50,940 SHE NEEDS AGGRESSIVE MANAGEMENT 5696 04:11:50,940 --> 04:11:53,209 TO HELP HER SURVIVE TO A RIPE 5697 04:11:53,209 --> 04:12:01,384 OLD AGE. 5698 04:12:01,384 --> 04:12:01,684 ARE 5699 04:12:01,684 --> 04:12:04,487 >> ARE THERE OTHER THERAPIES 5700 04:12:04,487 --> 04:12:05,855 OTHER THAN CURATIVE THERAPIES 5701 04:12:05,855 --> 04:12:09,258 YOU'D RECOMMEND FOR THIS PERSON? 5702 04:12:09,258 --> 04:12:15,698 >> WELL, TO ME HER SECOND BEST 5703 04:12:15,698 --> 04:12:17,533 THERAPY WOULD BE CHRONIC 5704 04:12:17,533 --> 04:12:18,834 TRANSFUSION THERAPY. 5705 04:12:18,834 --> 04:12:21,137 WE SEE THIS ALL THE TIME WHERE 5706 04:12:21,137 --> 04:12:22,938 PEOPLE WITH COGNITIVE DEFICITS 5707 04:12:22,938 --> 04:12:24,240 AND SHE'S HAD MORE THAN ONE 5708 04:12:24,240 --> 04:12:24,473 STROKE. 5709 04:12:24,473 --> 04:12:27,443 IT'S NOT A SURPRISE SHE HAS 5710 04:12:27,443 --> 04:12:28,944 COGNITIVE DEFICIT AND CONCERNED 5711 04:12:28,944 --> 04:12:31,747 AND SHOULD BE ABLE TO NAVIGATE 5712 04:12:31,747 --> 04:12:33,449 THIS WITHOUT ANY PROBLEM BUT 5713 04:12:33,449 --> 04:12:35,184 THAT'S NOT HOW IT WORKS IN THE 5714 04:12:35,184 --> 04:12:36,218 REAL WORLD. 5715 04:12:36,218 --> 04:12:39,221 THIS IS SOMEONE WHO I WOULD 5716 04:12:39,221 --> 04:12:42,958 ASSIGN A COMMUNITY HEALTH WORKER 5717 04:12:42,958 --> 04:12:45,127 TEXTING HER AND MAKING SURE 5718 04:12:45,127 --> 04:12:53,669 SHE'S MAKING HER APPOINTMENT AND 5719 04:12:53,669 --> 04:12:54,670 USE ALL THESE THINGS FOR HER 5720 04:12:54,670 --> 04:13:05,114 COMPLEX MEDICAL CONDITION. 5721 04:13:09,819 --> 04:13:12,288 >> IN PEDIATRICS WHERE WE HAVE A 5722 04:13:12,288 --> 04:13:14,423 PATIENT WHO HAD STROKE AND THEN 5723 04:13:14,423 --> 04:13:17,727 DEVELOP MOYAMOYA THEY TRY TO DO 5724 04:13:17,727 --> 04:13:19,428 SURGERY BEFORE THEY CAN BE 5725 04:13:19,428 --> 04:13:29,972 CONSIDERED FOR OTHER THERAPIES. 5726 04:13:35,377 --> 04:13:37,546 AND NOT DO THE SURGERY BECAUSE 5727 04:13:37,546 --> 04:13:39,582 IT'S COMPLICATED AND I TRY NOT 5728 04:13:39,582 --> 04:13:43,853 TO DO TRANS PLANT FOR AT LEAST 5729 04:13:43,853 --> 04:13:45,321 AROUND ONE YEAR AFTER SURGICAL 5730 04:13:45,321 --> 04:13:46,222 INTERVENTION LIKE THAT. 5731 04:13:46,222 --> 04:13:48,791 IT WOULD BE IMPORTANT TO BE 5732 04:13:48,791 --> 04:13:53,729 CAUTIOUS AND CONSULT THE FAMILY 5733 04:13:53,729 --> 04:14:01,937 ABOUT THAT BECAUSE AND WE WOULD 5734 04:14:01,937 --> 04:14:05,808 NEED TO KEEP HER FOR SUPPORT. 5735 04:14:05,808 --> 04:14:07,643 IF YOU DON'T DISCUSS THE 5736 04:14:07,643 --> 04:14:11,147 SURGICAL APPROACH I THINK THREE 5737 04:14:11,147 --> 04:14:13,182 MONTHS USUALLY OF RED BLOOD CELL 5738 04:14:13,182 --> 04:14:15,151 EXCHANGE TRYING DO THAT 5739 04:14:15,151 --> 04:14:16,118 PRECONDITIONING THERAPY WOULD BE 5740 04:14:16,118 --> 04:14:18,420 IMPORTANT FOR THE PATIENT TO GET 5741 04:14:18,420 --> 04:14:22,625 INTO A BETTER CLINICAL STATUS 5742 04:14:22,625 --> 04:14:26,662 AND DO THAT FOR REHEARSAL TO SEE 5743 04:14:26,662 --> 04:14:28,664 IF THEY CAN ADHERE WITH THE 5744 04:14:28,664 --> 04:14:29,765 COMPLEXITY OF BONE MARROW 5745 04:14:29,765 --> 04:14:33,135 TRANSPLANT PROCESS. 5746 04:14:33,135 --> 04:14:34,904 I TRY TO GIVE THEM THREE MONTHS 5747 04:14:34,904 --> 04:14:38,674 TO SEE IF THEY CAN FOLLOW THE 5748 04:14:38,674 --> 04:14:39,475 STANDARDS AND RED BLOOD CELL 5749 04:14:39,475 --> 04:14:44,513 EXCHANGE PLUS I WOULD ADD 5750 04:14:44,513 --> 04:14:46,849 HYDROXYUREA AND IF THE 5751 04:14:46,849 --> 04:14:49,051 COMBINATION THERAPY WOULD BE 5752 04:14:49,051 --> 04:14:50,085 POSSIBLE BECAUSE FOR ALL THE 5753 04:14:50,085 --> 04:14:52,021 HAPLO TRANSPLANT WE TRY TO GET 5754 04:14:52,021 --> 04:14:57,960 THE HYDROXYUREA AS HIGH AS 30 5755 04:14:57,960 --> 04:15:00,462 MILLIGRAM PER KILO. 5756 04:15:00,462 --> 04:15:02,932 IT COULD BE A CHALLENGE 5757 04:15:02,932 --> 04:15:03,999 SOMETIMES BUT TO DEMONSTRATE 5758 04:15:03,999 --> 04:15:04,633 COMPLIANCE WITH THERAPY WOULD BE 5759 04:15:04,633 --> 04:15:09,672 GOOD. 5760 04:15:09,672 --> 04:15:11,774 >> WE DIDN'T TALK ABOUT 5761 04:15:11,774 --> 04:15:12,708 FERTILITY PRESERVATION AND PART 5762 04:15:12,708 --> 04:15:14,176 OF THE CONVERSATION AND PLANNING 5763 04:15:14,176 --> 04:15:16,679 AND MAYBE A REASON WHY YOU WOULD 5764 04:15:16,679 --> 04:15:20,516 HOLD OFF POTENTIALLY ON DOING 5765 04:15:20,516 --> 04:15:22,451 HYDROXYUREA AND SOMETHING THAT 5766 04:15:22,451 --> 04:15:23,319 NEEDS TO BE DISCUSSED AND 5767 04:15:23,319 --> 04:15:25,521 ADDRESSED BEFORE MOVING FORWARD. 5768 04:15:25,521 --> 04:15:27,523 >> DO YOU HAVE A PREFERRED 5769 04:15:27,523 --> 04:15:32,061 TIMING IN RELATIONSHIP TO 5770 04:15:32,061 --> 04:15:35,464 TRANSFUSION WITH THE FERTILITY 5771 04:15:35,464 --> 04:15:35,798 PRESERVATION? 5772 04:15:35,798 --> 04:15:36,599 FOR SOMEONE WHO WOULDN'T 5773 04:15:36,599 --> 04:15:39,468 OTHERWISE BE ON TRANSFUSION. 5774 04:15:39,468 --> 04:15:45,074 >> OFF HYDROXYUREA? 5775 04:15:45,074 --> 04:15:48,777 ABOUT THREE MONTHS. 5776 04:15:48,777 --> 04:15:50,179 THERE'S NO DATA BUT OUT SEEMS 5777 04:15:50,179 --> 04:15:51,814 LIKE A GOOD NUMBER OF HALF LIVES 5778 04:15:51,814 --> 04:15:54,316 TO GET OUT OF THE SYSTEM AND 5779 04:15:54,316 --> 04:16:00,189 THEN SORT OF AS THEY PLAN FOR 5780 04:16:00,189 --> 04:16:01,190 TRANSPLANT AND FERTILITY 5781 04:16:01,190 --> 04:16:04,526 PRESERVATION AND MOVE TO 5782 04:16:04,526 --> 04:16:05,261 TRANSPLANT. 5783 04:16:05,261 --> 04:16:06,929 >> WELL, THANK YOU. 5784 04:16:06,929 --> 04:16:12,401 WE'RE GOING TO TAKE QUESTIONS 5785 04:16:12,401 --> 04:16:17,506 FOR BOTH QUESTIONS AFTER. 5786 04:16:17,506 --> 04:16:19,642 >> I WANTED TO SAY THIS IS CLOSE 5787 04:16:19,642 --> 04:16:22,711 TO MY HEART IT'S IMPORTANT NO 5788 04:16:22,711 --> 04:16:25,247 MATTER WHAT CHOICE SHE CHOOSES 5789 04:16:25,247 --> 04:16:29,351 TO FOLLOW LONG TERM WE HAVE A 5790 04:16:29,351 --> 04:16:31,153 PATIENT WHO WAS TRANSPLANTED SO 5791 04:16:31,153 --> 04:16:32,521 YEARS AND HER SYMPTOMS WERE 5792 04:16:32,521 --> 04:16:38,460 REVERSES AND SHE WOUND UP HAVING 5793 04:16:38,460 --> 04:16:40,963 AN INTRACRANIAL HEMORRHAGE 10 5794 04:16:40,963 --> 04:16:42,598 YEARS AFTER THE TRANSPLANT SO 5795 04:16:42,598 --> 04:16:44,400 IT'S IMPORTANT TO FOLLOW THE 5796 04:16:44,400 --> 04:16:45,301 PATIENT NO MATTER WHAT OPTION 5797 04:16:45,301 --> 04:16:47,269 YOU CHOOSE. 5798 04:16:47,269 --> 04:16:48,037 >> THANK YOU. 5799 04:16:48,037 --> 04:16:58,580 CAN I HAVE SLIDES BACK, PLEASE. 5800 04:17:04,720 --> 04:17:08,490 >> I'M GOING TO PRESENT OUR 5801 04:17:08,490 --> 04:17:11,160 SECOND CASE AND AFTER THIS WE'LL 5802 04:17:11,160 --> 04:17:13,495 HAVE GOOD FITZHUGH DOING THE 5803 04:17:13,495 --> 04:17:13,796 DISCUSSION. 5804 04:17:13,796 --> 04:17:18,968 THIS IS 40-YEAR-OLD WOMAN WITH 5805 04:17:18,968 --> 04:17:23,305 HEMOGLOBIN SC DISEASE AND IDDM 5806 04:17:23,305 --> 04:17:25,140 SINCE A TEENAGER AND WANTS TO 5807 04:17:25,140 --> 04:17:26,675 IMPROVE QUALITY AND FUNCTION OF 5808 04:17:26,675 --> 04:17:29,578 LIFE AND PREVENT EPISODES OF 5809 04:17:29,578 --> 04:17:32,081 SEVERE PAINFUL VASO OCCLUSIVE 5810 04:17:32,081 --> 04:17:32,281 EVENT. 5811 04:17:32,281 --> 04:17:37,720 SHE OFTEN HAS EPISODES OF 5812 04:17:37,720 --> 04:17:41,156 HYPERGLYCEMIA AND PREFERS GENE 5813 04:17:41,156 --> 04:17:46,295 THERAPY DESPITE NO DATA IN 5814 04:17:46,295 --> 04:17:48,097 PEOPLE WITH HEMOGLOBIN SC 5815 04:17:48,097 --> 04:17:53,068 DISEASE. 5816 04:17:53,068 --> 04:17:59,842 SHE CURRENTLY IS ON TWO DISEASE 5817 04:17:59,842 --> 04:18:05,481 MODIFYING THERAPIES, 5818 04:18:05,481 --> 04:18:08,951 CRIZANLIZUMAM AND HU AND 5819 04:18:08,951 --> 04:18:10,519 HOSPITALIZED FOR THREE AND THREE 5820 04:18:10,519 --> 04:18:14,456 SICKLE CELL VISITS PER YEAR FOR 5821 04:18:14,456 --> 04:18:16,058 PAIN AND HAS ACUTE CHEST 5822 04:18:16,058 --> 04:18:17,159 SYNDROME THREE TIMES BUT NOT 5823 04:18:17,159 --> 04:18:20,529 REQUIRED INTENSIVE CARE UNIT 5824 04:18:20,529 --> 04:18:22,898 ADMISSION OR RED CELL EXCHANGE 5825 04:18:22,898 --> 04:18:27,403 AND HAD A LEFT HIP REPLACEMENT 5826 04:18:27,403 --> 04:18:29,772 IN 2023 THAT SHOULD BE 2022 AND 5827 04:18:29,772 --> 04:18:32,041 RIGHT IN 2023. 5828 04:18:32,041 --> 04:18:35,778 AND LASER TREATMENT OF SICKLE 5829 04:18:35,778 --> 04:18:46,088 CELL RETINOPATHY. 5830 04:19:03,639 --> 04:19:14,283 AND HAD NORM AL CARDIAC FUNCTIO 5831 04:19:16,552 --> 04:19:26,929 AND SHOW HAS EGFR OF 117. 5832 04:19:33,602 --> 04:19:34,670 SO OUR FIRST DISCUSSION QUESTION 5833 04:19:34,670 --> 04:19:40,509 IS THE EFFICACY OF GENE THERAPY 5834 04:19:40,509 --> 04:19:50,285 VERSUS HAPLO IDENTICAL STEM CELL 5835 04:19:50,285 --> 04:19:50,819 THERAPY. 5836 04:19:50,819 --> 04:19:53,122 >> PEOPLE WITH HEMOGLOBIN SC 5837 04:19:53,122 --> 04:19:54,323 DISEASE HAVE BEEN EXCLUDED FROM 5838 04:19:54,323 --> 04:19:57,192 THE TRIALS SO WE HAVE NO DATA TO 5839 04:19:57,192 --> 04:19:59,695 KNOW WHETHER SHE WOULD BENEFIT 5840 04:19:59,695 --> 04:20:05,968 OR NOT OR EVEN WITH INCREASING 5841 04:20:05,968 --> 04:20:09,071 FETAL HEMOGLOBIN BECAUSE WE 5842 04:20:09,071 --> 04:20:09,771 CAN'T GET THEIR FETAL HEMOGLOBIN 5843 04:20:09,771 --> 04:20:11,406 HIGH SO WE DON'T KNOW IF IT WILL 5844 04:20:11,406 --> 04:20:13,275 BE BENEFICIAL. 5845 04:20:13,275 --> 04:20:14,977 I FOUND ONE CASE REPORT OF 5846 04:20:14,977 --> 04:20:17,713 SOMEONE WITH A PERSISTENCE OF 5847 04:20:17,713 --> 04:20:20,983 FETAL HEMOGLOBIN OF 25% A 5848 04:20:20,983 --> 04:20:21,483 28-YEAR-OLD AROUND THE 5849 04:20:21,483 --> 04:20:24,386 HEMOGLOBIN WAS NORMAL. 5850 04:20:24,386 --> 04:20:26,855 IT'S POSSIBLE SHE MAY BENEFIT 5851 04:20:26,855 --> 04:20:29,057 FROM A HIGHER HEMOGLOBIN LEVEL 5852 04:20:29,057 --> 04:20:32,528 BUT WE JUST DON'T KNOW WHERE 5853 04:20:32,528 --> 04:20:36,598 THERE'S MORE DATA WITH HAPLO 5854 04:20:36,598 --> 04:20:40,502 TRANSPLANTATION AND MANY HAVE 5855 04:20:40,502 --> 04:20:44,506 GONE THROUGH THE TRANSPLANT WITH 5856 04:20:44,506 --> 04:20:46,408 REVERSAL OF SICKLE CELL DISEASE 5857 04:20:46,408 --> 04:20:48,877 AND WOULD FEEL MORE COMFORTABLE 5858 04:20:48,877 --> 04:20:50,579 RECOMMENDING THAT THAN GENE 5859 04:20:50,579 --> 04:20:51,880 THERAPY FOR THE PATIENT. 5860 04:20:51,880 --> 04:20:54,516 >> I'LL TAKE THE CONTRARIAN 5861 04:20:54,516 --> 04:20:57,553 APPROACH WHILE THERE'S NO DATA I 5862 04:20:57,553 --> 04:20:58,587 DON'T THINK THERE'S CLINICAL 5863 04:20:58,587 --> 04:21:01,089 TRIAL DATA FOR PEOPLE WITH SC. 5864 04:21:01,089 --> 04:21:02,758 WHEN THE FDA APPROVED THE 5865 04:21:02,758 --> 04:21:03,825 PRODUCT THEY INCLUDED SICKLE 5866 04:21:03,825 --> 04:21:06,929 CELL DISEASE NOT JUST PEOPLE 5867 04:21:06,929 --> 04:21:15,304 WITH SS AND BETA CELL ALLO 5868 04:21:15,304 --> 04:21:18,640 THEMIA AND I THINK WE NEED TO 5869 04:21:18,640 --> 04:21:23,812 EXPLORE WHAT HER INTEREST IS IN 5870 04:21:23,812 --> 04:21:28,283 GENE THERAPY AND MAKE SURE WE 5871 04:21:28,283 --> 04:21:30,919 LISTEN TO HER VOICE AND 5872 04:21:30,919 --> 04:21:31,853 INCORPORATE THAT INTO THE 5873 04:21:31,853 --> 04:21:33,222 DECISION MAKING AND TRY TO 5874 04:21:33,222 --> 04:21:35,257 UNDERSTAND WHY SHE HAS A STRONG 5875 04:21:35,257 --> 04:21:35,791 PREFERENCE. 5876 04:21:35,791 --> 04:21:37,125 I'M NOT SURE. 5877 04:21:37,125 --> 04:21:40,128 I WASN'T THERE WHEN SHE MET WITH 5878 04:21:40,128 --> 04:21:43,899 THE CELLULAR THERAPY EXPERT IF 5879 04:21:43,899 --> 04:21:47,936 THAT'S WHAT CAME FROM THE 5880 04:21:47,936 --> 04:21:48,337 MEETING. 5881 04:21:48,337 --> 04:21:58,880 IT'S A FOLLOW UP TO ONE EARLIER. 5882 04:21:59,281 --> 04:22:02,084 >> THE SAFETY OF GENE THERAPY 5883 04:22:02,084 --> 04:22:05,787 VERSUS HAP LOW TRANSPLANT IN 5884 04:22:05,787 --> 04:22:08,724 SOMEONE AGE 40, I LOOKED AT THE 5885 04:22:08,724 --> 04:22:09,825 LITERATURE IN PEOPLE WITH SICKLE 5886 04:22:09,825 --> 04:22:12,594 CELL DISEASE AND THERE'S A LACK 5887 04:22:12,594 --> 04:22:16,231 OF INSUFFICIENT DATA HOW MILO 5888 04:22:16,231 --> 04:22:17,766 ABLATIVE CONDITIONS AFFECTS 5889 04:22:17,766 --> 04:22:22,938 ADULTS WITH SICKLE CELL DISEASE. 5890 04:22:22,938 --> 04:22:24,239 WE KNOW THEY'VE BEEN ENROLLED 5891 04:22:24,239 --> 04:22:26,742 WITH ANY SIGNIFICANT ORGAN 5892 04:22:26,742 --> 04:22:32,047 DAMAGE HAVE BEEN EXCLUDED FROM 5893 04:22:32,047 --> 04:22:33,282 THE STUDY. 5894 04:22:33,282 --> 04:22:35,617 WE DO KNOW IN THE BIO STUDY DID 5895 04:22:35,617 --> 04:22:38,720 PASS AWAY BUT THAT PATIENT HAD A 5896 04:22:38,720 --> 04:22:43,358 HISTORY OF PULMONARY 5897 04:22:43,358 --> 04:22:44,259 HYPERTENSION THEY DON'T HAVE 5898 04:22:44,259 --> 04:22:45,694 SIGNIFICANT ORGAN DAMAGE 5899 04:22:45,694 --> 04:22:48,530 REPORTED. 5900 04:22:48,530 --> 04:22:52,868 WE KNOW OLDER PATIENTS WHEN THE 5901 04:22:52,868 --> 04:22:56,505 TRANSPLANTS INCLUDED ABLATIVE 5902 04:22:56,505 --> 04:22:59,808 CONDITIONS MORTALITY WAS HIGHER 5903 04:22:59,808 --> 04:23:02,678 IN ADULTS IN GRAPH VERSUS 5904 04:23:02,678 --> 04:23:03,078 ADULTS. 5905 04:23:03,078 --> 04:23:06,048 I DON'T THINK THERE'S ENOUGH 5906 04:23:06,048 --> 04:23:09,217 DATA TO KNOW HOW MANY 5907 04:23:09,217 --> 04:23:10,852 40-YEAR-OLDS UNDER GO THE 5908 04:23:10,852 --> 04:23:13,422 CONDITION WILL SURVIVE AND 5909 04:23:13,422 --> 04:23:15,223 THERE'S MORE DATA WITH 5910 04:23:15,223 --> 04:23:17,292 CONDITIONING AND NON-ABLATIVE 5911 04:23:17,292 --> 04:23:20,195 CONDITIONING WHERE ADULTS HAVE 5912 04:23:20,195 --> 04:23:23,432 SUCCESSFULLY GONE THROUGH 5913 04:23:23,432 --> 04:23:26,168 TRANSPLANT WHO ARE DOING WELL 5914 04:23:26,168 --> 04:23:27,235 WITHOUT SICKLE CELL DISEASE. 5915 04:23:27,235 --> 04:23:29,137 FOR THAT REASON I FEEL MORE 5916 04:23:29,137 --> 04:23:30,205 COMFORTABLE BUT I DO THINK IT'S 5917 04:23:30,205 --> 04:23:32,774 IMPORTANT TO TALK TO THE PATIENT 5918 04:23:32,774 --> 04:23:35,610 EVEN IF THE PATIENT HAD SS 5919 04:23:35,610 --> 04:23:38,413 DISEASE ABOUT THE LACK OF DATA 5920 04:23:38,413 --> 04:23:48,523 AND INCORPORATE THEIR 5921 04:23:48,523 --> 04:23:48,824 PREFERENCES. 5922 04:23:48,824 --> 04:23:55,297 >> I SHARE YOUR OPINION WITH 5923 04:23:55,297 --> 04:23:56,631 SOMEONE 40 WITH SICKLE CELL 5924 04:23:56,631 --> 04:23:58,934 DISEASE AND WONDER IF IT'S 5925 04:23:58,934 --> 04:24:01,870 EASIER WITH SC VERSUS SS. 5926 04:24:01,870 --> 04:24:02,904 I THINK THE EXPERIENCE MOVING 5927 04:24:02,904 --> 04:24:05,173 FROM YOUNG ADULTS TO SLIGHTLY 5928 04:24:05,173 --> 04:24:15,684 OLDER THAN YOUNG ADULTS MORE 5929 04:24:16,551 --> 04:24:21,356 MYELOABLAH YOU -- MYELOABLATIVE 5930 04:24:21,356 --> 04:24:25,360 CONDITIONS AND THEY DO POORLY 5931 04:24:25,360 --> 04:24:27,529 AND I REALLY RECOMMEND CAUTION 5932 04:24:27,529 --> 04:24:28,864 IN THAT AREA AND I THINK ONE OF 5933 04:24:28,864 --> 04:24:32,501 THE THINGS THAT WE NEED TO LEARN 5934 04:24:32,501 --> 04:24:35,470 AS WE EXPAND FROM CLINICAL 5935 04:24:35,470 --> 04:24:37,172 TRIALS TO CLINICAL EXPERIENCE 5936 04:24:37,172 --> 04:24:38,940 WITH MORE DIVERSE PATIENT 5937 04:24:38,940 --> 04:24:42,144 POPULATION HOW WELL DO PEOPLE 5938 04:24:42,144 --> 04:24:43,512 TOLERATE IT AND HOW MUCH ORGAN 5939 04:24:43,512 --> 04:24:45,781 FUNCTION CAN WE GET AWAY WITH 5940 04:24:45,781 --> 04:24:47,916 FOR OLDER AGED PEOPLE BEFORE WE 5941 04:24:47,916 --> 04:24:52,521 GET INTO TROUBLE AND I THINK 5942 04:24:52,521 --> 04:24:56,291 THERE'S AN ISSUE BROUGHT UP OF 5943 04:24:56,291 --> 04:24:56,625 HEMATOPOIESIS. 5944 04:24:56,625 --> 04:24:59,494 >> I TALKED EARLIER ABOUT THE 5945 04:24:59,494 --> 04:25:00,529 RISK OF CLINICAL HEMATOPOIESIS 5946 04:25:00,529 --> 04:25:07,636 AND WE DON'T KNOW THAT IN 5947 04:25:07,636 --> 04:25:08,203 PATIENTS WITH SICKLE CELL 5948 04:25:08,203 --> 04:25:10,572 DISEASE AND THERE'S THOUSANDS OF 5949 04:25:10,572 --> 04:25:11,373 PATIENTS BEING SEQUENCED FROM 5950 04:25:11,373 --> 04:25:13,408 CHILDREN TO OLDER ADULTS. 5951 04:25:13,408 --> 04:25:14,776 SO WE'RE GOING TO HAVE THE 5952 04:25:14,776 --> 04:25:16,912 ANSWER SOON BUT WE KNOW IN THE 5953 04:25:16,912 --> 04:25:19,414 GENERAL POPULATION OLDER PEOPLE 5954 04:25:19,414 --> 04:25:22,284 ARE MORE AT RISK FOR CLINICAL 5955 04:25:22,284 --> 04:25:23,418 HEMATOPOIESIS AND IF THE PATIENT 5956 04:25:23,418 --> 04:25:25,754 HAS THIS THERE WILL BE A RISK 5957 04:25:25,754 --> 04:25:27,756 POTENTIALLY WITH GENE THERAPY 5958 04:25:27,756 --> 04:25:31,927 AND CLONAL EVOLUTION WITH THE 5959 04:25:31,927 --> 04:25:32,761 PROLIFERATIVE STRESS ASSOCIATED 5960 04:25:32,761 --> 04:25:38,567 WITH THE RECONSTITUTION AND 5961 04:25:38,567 --> 04:25:42,971 RECOMMEND THE REDUCED CHIMERISM 5962 04:25:42,971 --> 04:25:44,072 IN THIS PATIENT. 5963 04:25:44,072 --> 04:25:46,174 >> WE DON'T KNOW ABOUT THE RISK 5964 04:25:46,174 --> 04:25:47,476 OF HEMATOPOIESIS FOR SC. 5965 04:25:47,476 --> 04:25:51,112 PEOPLE WITH SS HAVE BEEN OVER 5966 04:25:51,112 --> 04:25:51,413 REPRESENTED. 5967 04:25:51,413 --> 04:25:53,315 IF THINK OF THE 5968 04:25:53,315 --> 04:25:54,015 PATHOPHYSIOLOGICAL MECHANISMS 5969 04:25:54,015 --> 04:25:55,784 YOU REFERRED TO IN YOUR TALK, 5970 04:25:55,784 --> 04:25:57,819 MANY ARE LESS INTENSE FOR PEOPLE 5971 04:25:57,819 --> 04:26:00,422 WITH SC SO PERHAPS THEIR RISK IS 5972 04:26:00,422 --> 04:26:01,523 LOWER BUT THE LARGE POPULATION 5973 04:26:01,523 --> 04:26:09,231 STUDY LOOKING AT ACUTE MYELOID 5974 04:26:09,231 --> 04:26:10,232 LEUKEMIA SEPARATES THAT OUT. 5975 04:26:10,232 --> 04:26:13,001 I DON'T THINK WE KNOW ABOUT HER 5976 04:26:13,001 --> 04:26:15,403 RISK SPECIFICALLY COMPARED TO 5977 04:26:15,403 --> 04:26:19,040 OTHER PEOPLE WITH SICKLE CELL 5978 04:26:19,040 --> 04:26:19,274 DISEASE. 5979 04:26:19,274 --> 04:26:20,308 AND THE FINAL QUESTION WELL, 5980 04:26:20,308 --> 04:26:21,376 THERE'S TWO MORE. 5981 04:26:21,376 --> 04:26:26,748 THE NEXT ONE WAS HOW DOES HER 5982 04:26:26,748 --> 04:26:30,151 HISTORY OF INSULIN DEPENDENT 5983 04:26:30,151 --> 04:26:33,622 DIABETES MYELITIS CHANGE HER 5984 04:26:33,622 --> 04:26:36,491 RISK FOR CURATIVE THERAPIES. 5985 04:26:36,491 --> 04:26:39,528 >> I DON'T KNOW AS MUCH AND SURE 5986 04:26:39,528 --> 04:26:41,263 THERE HAVEN'T BEEN A LOT OF 5987 04:26:41,263 --> 04:26:42,764 PEOPLE WITH DIABETES WHO 5988 04:26:42,764 --> 04:26:44,165 RECEIVED GENE THERAPY SO I CAN'T 5989 04:26:44,165 --> 04:26:45,767 SPEAK TO THAT RISK AS MUCH. 5990 04:26:45,767 --> 04:26:47,802 THERE'S MORE ORGAN DAMAGE 5991 04:26:47,802 --> 04:26:48,537 POSSIBLE WITH DIABETES. 5992 04:26:48,537 --> 04:26:52,073 IT'S POSSIBLE SHE MAY HAVE MORE 5993 04:26:52,073 --> 04:26:53,308 SUBCLINICAL ORGAN DAMAGE RELATED 5994 04:26:53,308 --> 04:26:54,809 TO DIABETES WE DON'T KNOW ABOUT 5995 04:26:54,809 --> 04:26:56,945 BUT WITH HAPLO IDENTICAL 5996 04:26:56,945 --> 04:26:58,780 TRANSPLANT WITH THE 5997 04:26:58,780 --> 04:26:59,447 IMMUNOSUPPRESSANT GIVEN THERE'S 5998 04:26:59,447 --> 04:27:01,983 A RISK FOR DIABETES SO IT COULD 5999 04:27:01,983 --> 04:27:03,451 POTENTIALLY MAKE THE DIABETES 6000 04:27:03,451 --> 04:27:05,720 WORSE IF SHE WERE TO DEVELOP 6001 04:27:05,720 --> 04:27:07,556 GRAFT VERSUS HOST DISEASE AND 6002 04:27:07,556 --> 04:27:08,757 START STEROIDS THAT WOULD BE A 6003 04:27:08,757 --> 04:27:11,126 CORNER WITH SOMEBODY WITH 6004 04:27:11,126 --> 04:27:13,228 DIABETES BUT WE COLLABORATE 6005 04:27:13,228 --> 04:27:14,296 CLOSELY WITH OUR ENDOCRINE TEAM 6006 04:27:14,296 --> 04:27:15,931 AND GIVE APPROPRIATE TREATMENT. 6007 04:27:15,931 --> 04:27:21,303 I WOULDN'T HAVE A CONCERN FOR 6008 04:27:21,303 --> 04:27:23,038 SPECIALLY HOW THIS IS FOR 6009 04:27:23,038 --> 04:27:23,605 SOMEBODY WITH DIABETES. 6010 04:27:23,605 --> 04:27:25,473 >> I TRIED TO ADDRESS THE 6011 04:27:25,473 --> 04:27:27,976 QUESTION BY LOOKING AT THE 6012 04:27:27,976 --> 04:27:28,710 GENERAL TRANSPLANT LITERATURE. 6013 04:27:28,710 --> 04:27:31,580 AT LEAST IN ONE LARGE ADULT 6014 04:27:31,580 --> 04:27:35,550 SERIES ABOUT 6% OF PATIENTS HAD 6015 04:27:35,550 --> 04:27:38,186 DIABETES PRIOR TO TRANSPLANT 6016 04:27:38,186 --> 04:27:40,455 LOOKING MOSTLY AT MOSTLY OLDER 6017 04:27:40,455 --> 04:27:46,094 ADULTS AND THE MEAN AGE WAS 60% 6018 04:27:46,094 --> 04:27:51,399 WITH DIABETES AND THE GROUP THAT 6019 04:27:51,399 --> 04:27:54,903 DEVELOPED AND SOME MAY BE THE 6020 04:27:54,903 --> 04:27:57,305 DIABETES, SOME MAY BE THE REASON 6021 04:27:57,305 --> 04:28:01,710 THEY DEVELOP MORE FOCUSSED 6022 04:28:01,710 --> 04:28:02,577 IMMUNOSUPPRESSION BUT THE 6023 04:28:02,577 --> 04:28:04,846 INCIDENT OF DIABETES AFTER 6024 04:28:04,846 --> 04:28:06,081 TRANSPLANT IS ASSOCIATED WITH 6025 04:28:06,081 --> 04:28:07,215 SUBSTANTIALLY WORSE OUTCOMES 6026 04:28:07,215 --> 04:28:08,617 RELATED TO MORTALITY AND THE 6027 04:28:08,617 --> 04:28:10,719 PEOPLE THAT WENT TO TRANSPLANT 6028 04:28:10,719 --> 04:28:13,254 DID HAVE SOME INCREASED RISK OF 6029 04:28:13,254 --> 04:28:15,290 OTHER CARDIOVASCULAR 6030 04:28:15,290 --> 04:28:15,957 COMPLICATIONS SUCH AS 6031 04:28:15,957 --> 04:28:17,726 HYPERTENSION AND STROKE. 6032 04:28:17,726 --> 04:28:19,094 SO I THINK IT MY INCREASE THE 6033 04:28:19,094 --> 04:28:21,496 RISK SOME. 6034 04:28:21,496 --> 04:28:29,771 SHE USES INSULIN PUMP AND IT'S 6035 04:28:29,771 --> 04:28:32,007 BASED ON THERAPY AND HOW CLEARLY 6036 04:28:32,007 --> 04:28:36,978 EVEN THE NON-MYELOABLATIVE 6037 04:28:36,978 --> 04:28:38,413 CONDITION CONDITION AFFECT YOUR 6038 04:28:38,413 --> 04:28:43,918 ABILITY TO EAT OVER TIME BUT MAY 6039 04:28:43,918 --> 04:28:45,820 BE MANAGEABLE OVER TIME. 6040 04:28:45,820 --> 04:28:47,188 THE LAST TOPIC FOR DISCUSSION IS 6041 04:28:47,188 --> 04:28:49,424 WHETHER THERE'S OTHER THERAPIES 6042 04:28:49,424 --> 04:28:52,160 WE CAN CONSIDER OTHER THAN 6043 04:28:52,160 --> 04:28:53,561 CURATIVE THERAPIES THAT MAY 6044 04:28:53,561 --> 04:28:55,363 AFFECT SICKLE CELL DISEASE. 6045 04:28:55,363 --> 04:28:57,565 CURRENTLY SHE'S ON OUR BEST 6046 04:28:57,565 --> 04:28:58,867 COMBINATION OF MEDICATIONS SHORT 6047 04:28:58,867 --> 04:29:02,971 OF TRANSFUSION FOR MANAGING 6048 04:29:02,971 --> 04:29:04,839 ACUTE COMPLICATIONS OF SICKLE 6049 04:29:04,839 --> 04:29:12,480 CELL DISEASE AND WE COULD NINK 6050 04:29:12,480 --> 04:29:15,050 -- THINK OF RED CELL EXCHANGES 6051 04:29:15,050 --> 04:29:21,356 FOR SICKLE CELL. 6052 04:29:21,356 --> 04:29:23,792 >> RELATED TO THE AGE OF THE 6053 04:29:23,792 --> 04:29:27,996 PATIENT, 40, I PERSONALLY THINK 6054 04:29:27,996 --> 04:29:29,397 WE SHOULDN'T DISCRIMINATE BASED 6055 04:29:29,397 --> 04:29:31,599 ON AGE AND LOOK AT 6056 04:29:31,599 --> 04:29:32,500 COMORBIDITIES. 6057 04:29:32,500 --> 04:29:37,305 IN BONE MARROW TRANSPLANT WE 6058 04:29:37,305 --> 04:29:40,341 HAVE A COMORBIDITY INDEX THAT 6059 04:29:40,341 --> 04:29:42,677 MAYBE WE CAN EXTRAPOLATE FOR 6060 04:29:42,677 --> 04:29:44,312 THIS PATIENT AND SEE IF THEY'RE 6061 04:29:44,312 --> 04:29:46,915 AT RISK FOR ANY TRANSPLANT 6062 04:29:46,915 --> 04:29:48,750 MORTALITY AND I WOULD PUT BOTH 6063 04:29:48,750 --> 04:29:52,487 GENE THERAPY AND HAPLO IN THE 6064 04:29:52,487 --> 04:29:53,788 SAME CATEGORY AND HAVING 6065 04:29:53,788 --> 04:29:56,224 DIABETES THAT WOULD BE COUNTED 6066 04:29:56,224 --> 04:29:59,427 AS ONE AND PUT HER IN TERMS OF 6067 04:29:59,427 --> 04:30:01,763 2% TO 5% OF THE RISK. 6068 04:30:01,763 --> 04:30:03,998 THIS WOULD BE EQUAL IN MY 6069 04:30:03,998 --> 04:30:04,232 OPINION. 6070 04:30:04,232 --> 04:30:07,502 AND I WOULD ALSO HIGHLIGHT THAT 6071 04:30:07,502 --> 04:30:10,705 MANY PATIENTS COME TO GENE 6072 04:30:10,705 --> 04:30:12,540 THERAPY THINKING IT'S SIMILAR TO 6073 04:30:12,540 --> 04:30:15,977 AN AUTOLOGOUS TRANSPLANT BUT THE 6074 04:30:15,977 --> 04:30:18,780 DIYNAMIC IS DIFFERENT. 6075 04:30:18,780 --> 04:30:20,548 YOU NEED SOMEONE WITH EXPERIENCE 6076 04:30:20,548 --> 04:30:24,519 AND BONE MARROW TRANSPLANT FOR 6077 04:30:24,519 --> 04:30:25,186 SICKLE CELL DISEASE BECAUSE THEY 6078 04:30:25,186 --> 04:30:26,955 REPRESENT ANECDOTALLY FROM MY 6079 04:30:26,955 --> 04:30:29,591 OWN EXPERIENCE WE HAD A PATIENT 6080 04:30:29,591 --> 04:30:31,226 THAT DEVELOPED PRESS WITH THE 6081 04:30:31,226 --> 04:30:33,595 USE OF GENE THERAPY. 6082 04:30:33,595 --> 04:30:35,830 WE HAVE TO BE CAREFUL WITH THE 6083 04:30:35,830 --> 04:30:37,766 PATIENT AND NOT JUST THINK THE 6084 04:30:37,766 --> 04:30:40,502 OTHER COMPLICATION RELATED TO 6085 04:30:40,502 --> 04:30:45,240 ALLO GENIC TRANSPLANT IN SICKLE 6086 04:30:45,240 --> 04:30:48,743 CELL AND THE PERIOD OF 6087 04:30:48,743 --> 04:30:50,578 NEUTROPENIA AND THEY ARE DON'T 6088 04:30:50,578 --> 04:30:52,714 ENGRAPH UNTIL DAY 24, 26. 6089 04:30:52,714 --> 04:30:55,617 THERE'S A SHIFT IN THE PERIOD 6090 04:30:55,617 --> 04:30:57,619 WHERE THERE'S A RISK OF 6091 04:30:57,619 --> 04:30:58,720 INFECTION AND OTHERS SEEM TO BE 6092 04:30:58,720 --> 04:30:59,687 POTENTIALLY DIFFERENT AND YOU 6093 04:30:59,687 --> 04:31:02,924 HAVE TO PAY ATTENTION TO THAT 6094 04:31:02,924 --> 04:31:11,533 AND LOOK MORE LIKE AN ALLO IN 6095 04:31:11,533 --> 04:31:13,001 HAPLO TRANSPLANT VERSUS GENE 6096 04:31:13,001 --> 04:31:13,268 THERAPY. 6097 04:31:13,268 --> 04:31:14,702 >> DO YOU THINK OF SICKLE CELL 6098 04:31:14,702 --> 04:31:17,005 DISEASE AS A COMORBIDITY WHEN 6099 04:31:17,005 --> 04:31:19,374 YOU THINK OF THE COMORBIDITY 6100 04:31:19,374 --> 04:31:21,309 INDEX? 6101 04:31:21,309 --> 04:31:22,143 YOU MENTIONED PEOPLE GETTING 6102 04:31:22,143 --> 04:31:23,278 PRESSED RELATED TO SICKLE CELL 6103 04:31:23,278 --> 04:31:26,815 DISEASE AND CHANGING IN THEIR 6104 04:31:26,815 --> 04:31:27,782 CEREBRAL HEMODYNAMICS IN 6105 04:31:27,782 --> 04:31:29,884 ADDITION TO THE MEDICATIONS 6106 04:31:29,884 --> 04:31:30,084 USED? 6107 04:31:30,084 --> 04:31:32,520 >> THAT'S WHERE WE NEED MORE 6108 04:31:32,520 --> 04:31:32,720 DATA. 6109 04:31:32,720 --> 04:31:34,255 THE COMORBIDITY INDEX IS MORE 6110 04:31:34,255 --> 04:31:41,696 FROM THE MALIGNANT AND PATIENTS 6111 04:31:41,696 --> 04:31:45,633 ANALYZED FROM THE DATA AND 6112 04:31:45,633 --> 04:31:47,702 DEVELOP A MORBIDITY INDEX THAT 6113 04:31:47,702 --> 04:31:50,038 COULD HELP FOR THE SHARED 6114 04:31:50,038 --> 04:31:51,206 MEDICAL DECISION. 6115 04:31:51,206 --> 04:31:53,842 IT'S GREAT WE HAVE OPTION. 6116 04:31:53,842 --> 04:31:56,511 ONE THING WE SHOULD HAVE IS 6117 04:31:56,511 --> 04:31:59,414 THERE'S MANY OPTION AND WE 6118 04:31:59,414 --> 04:32:02,784 SHOULD TALK TO THE PATIENT ABOUT 6119 04:32:02,784 --> 04:32:05,320 ALL THIS AND WHERE THERE'S 6120 04:32:05,320 --> 04:32:06,120 CONCERN BECAUSE EVEN GENE 6121 04:32:06,120 --> 04:32:08,122 THERAPY IS NOT THE SAME. 6122 04:32:08,122 --> 04:32:09,858 THERE'S SO MANY MODALITY THAT 6123 04:32:09,858 --> 04:32:11,359 NEED TO BE TAKEN INTO 6124 04:32:11,359 --> 04:32:11,693 CONSIDERATION. 6125 04:32:11,693 --> 04:32:12,493 >> THANK YOU. 6126 04:32:12,493 --> 04:32:13,895 I WANTED TO INVITE UP WE HAVE 6127 04:32:13,895 --> 04:32:15,363 ONE MORE IMPORTANT TO JOIN OUR 6128 04:32:15,363 --> 04:32:23,905 PANEL BEFORE WE UP -- OPEN IT 6129 04:32:23,905 --> 04:32:29,644 UP TO QUESTIONS AND THAT'S RAPI 6130 04:32:29,644 --> 04:32:39,787 DANIELS. 6131 04:32:43,858 --> 04:32:47,295 THANK YOU FOR COMING AND JOINING 6132 04:32:47,295 --> 04:32:48,529 US. 6133 04:32:48,529 --> 04:32:54,369 MS. SAMUELS IS OUR ONE EXPERT ON 6134 04:32:54,369 --> 04:32:56,938 GENE THERAPY AND SICKLE CELL 6135 04:32:56,938 --> 04:32:59,340 DISEASE THAT HAD GENE THERAPY SO 6136 04:32:59,340 --> 04:33:00,508 THANK YOU FOR COMING AND JOINING 6137 04:33:00,508 --> 04:33:01,943 US AND THEN I WANT TO OPEN IT UP 6138 04:33:01,943 --> 04:33:12,186 TO QUESTIONS. 6139 04:33:20,528 --> 04:33:23,898 >> THAT WAS A WONDERFUL LOVELY 6140 04:33:23,898 --> 04:33:25,366 CONVERSATION WITH EXPERTS. 6141 04:33:25,366 --> 04:33:26,868 THERE'S NOT A BETTER GROUP I'D 6142 04:33:26,868 --> 04:33:28,503 LOVE TO HEAR FROM. 6143 04:33:28,503 --> 04:33:31,572 SO SOPHI MADE THE POINT 6144 04:33:31,572 --> 04:33:32,473 ELOQUENTLY IN THE BEGINNING. 6145 04:33:32,473 --> 04:33:33,007 WE DON'T HAVE DATA. 6146 04:33:33,007 --> 04:33:36,511 WE DON'T KNOW. 6147 04:33:36,511 --> 04:33:39,814 THAT'S USUALLY TO THE ENDS OF A 6148 04:33:39,814 --> 04:33:40,715 CONVERSATION NOT THE BEGINNING 6149 04:33:40,715 --> 04:33:42,016 OF A LONG ONE. 6150 04:33:42,016 --> 04:33:45,820 THAT'S SOMETHING WE OUGHT TO 6151 04:33:45,820 --> 04:33:47,088 HAVE WITH HUMILITY TO ACCEPT WE 6152 04:33:47,088 --> 04:33:47,755 DON'T KNOW AND NOT LIKELY TO 6153 04:33:47,755 --> 04:33:50,658 KNOW. 6154 04:33:50,658 --> 04:33:53,628 SOME OF THE THINGS NOT BROUGHT 6155 04:33:53,628 --> 04:33:55,697 UP WAS THE BURDEN OF CARE OF SIX 6156 04:33:55,697 --> 04:33:58,499 MONTHS OR ONE YEAR OF 6157 04:33:58,499 --> 04:33:59,834 IMMUNOSUPPRESSION MAY BE VIEWED 6158 04:33:59,834 --> 04:34:04,305 DIFFERENTLY BY PATIENTS. 6159 04:34:04,305 --> 04:34:08,476 THEY'RE NOT JUST CONSIDERING 6160 04:34:08,476 --> 04:34:11,679 HAPLO VERSUS GENE THERAPY, 6161 04:34:11,679 --> 04:34:13,314 SECOND, OUTCOMES MAY ALSO BE 6162 04:34:13,314 --> 04:34:14,182 DISPARATE IN TERMS OF WHAT 6163 04:34:14,182 --> 04:34:15,750 THEY'RE LOOK BEING FOR. 6164 04:34:15,750 --> 04:34:17,085 SOME ARE SAYING MAYBE I'M STILL 6165 04:34:17,085 --> 04:34:18,619 GOING TO BE AT RISK FOR STROKE 6166 04:34:18,619 --> 04:34:20,488 BUT TODAY I'LL BE FREE OF PAIN 6167 04:34:20,488 --> 04:34:25,560 AND IF I CHOOSE TO DO THE GENE 6168 04:34:25,560 --> 04:34:27,061 THERAPY WHICH IS MORE ACCEPTABLE 6169 04:34:27,061 --> 04:34:28,863 TO ME AND PEOPLE MAY BREAK A 6170 04:34:28,863 --> 04:34:29,964 PART THE PIECES AND MAKE 6171 04:34:29,964 --> 04:34:31,899 DECISIONS DIFFERENTLY. 6172 04:34:31,899 --> 04:34:36,371 SO I WOULD AGREE WITH RABBI AND 6173 04:34:36,371 --> 04:34:38,773 MAYBE GO FURTHER I WOULD NOT 6174 04:34:38,773 --> 04:34:41,776 MAKE A RECOMMENDATION ONE WAY OR 6175 04:34:41,776 --> 04:34:44,979 THE OTHER IN CASE ONE BUT 6176 04:34:44,979 --> 04:34:48,549 DISCUSS ALL OF THE ABOUT AND A 6177 04:34:48,549 --> 04:34:50,918 QUICK COMMENT ABOUT PRESS. 6178 04:34:50,918 --> 04:34:55,923 PRESS IS A FAILURE OF CEREBRAL 6179 04:34:55,923 --> 04:35:00,361 AUTO REGULATION AND IN THE DATA 6180 04:35:00,361 --> 04:35:02,163 ON PRESS IN SICKLE CELL DISEASE 6181 04:35:02,163 --> 04:35:10,638 IT MOSTLY HAPPENED WITHOUT HIGH 6182 04:35:10,638 --> 04:35:12,373 CYCLOSPORIN LEVELS AND LIKE A 6183 04:35:12,373 --> 04:35:13,241 TRANSPLANT PEOPLE UNDERGOING 6184 04:35:13,241 --> 04:35:14,709 GENE THERAPY SHOULD BE CARED FOR 6185 04:35:14,709 --> 04:35:17,912 BY TEAMS THAT KNOW WHAT THEY'RE 6186 04:35:17,912 --> 04:35:18,112 DOING. 6187 04:35:18,112 --> 04:35:20,181 THANK YOU. 6188 04:35:20,181 --> 04:35:22,550 >> I THINK CHRIS YOU BRING UP AN 6189 04:35:22,550 --> 04:35:25,153 EXCELLENT POINT WE SHOULD TALK 6190 04:35:25,153 --> 04:35:28,056 ABOUT THE NEED FOR COMBINED 6191 04:35:28,056 --> 04:35:29,090 MANAGEMENT OF PATIENTS FROM 6192 04:35:29,090 --> 04:35:30,958 BEGINNING, MIDDLE AND END AND 6193 04:35:30,958 --> 04:35:33,294 POST END THE HEMATOLOGISTS AND 6194 04:35:33,294 --> 04:35:34,695 TRANSPLANTERS NEED TO WORK 6195 04:35:34,695 --> 04:35:36,864 TOGETHER IN A COMPREHENSIVE 6196 04:35:36,864 --> 04:35:38,066 APPROACH WITH POLICIES AND 6197 04:35:38,066 --> 04:35:40,535 PROCEDURES FOR ALL THIS BEFORE 6198 04:35:40,535 --> 04:35:50,711 YOU START. 6199 04:35:51,179 --> 04:35:54,048 >> I'LL DISCUSS EFFICACY AND 6200 04:35:54,048 --> 04:35:57,318 THEN WHAT MADE YOU DECIDE 6201 04:35:57,318 --> 04:35:59,320 BETWEEN GENE THERAPY AND HAPLO 6202 04:35:59,320 --> 04:35:59,687 TRANSPLANT. 6203 04:35:59,687 --> 04:36:01,155 >> THANK YOU FOR IF HE QUESTION. 6204 04:36:01,155 --> 04:36:06,627 I MADE THE DECISION AT THE TIME 6205 04:36:06,627 --> 04:36:08,863 I HAD TWO BROTHERS THAT WERE 10 6206 04:36:08,863 --> 04:36:10,164 AND 6, I BELIEVE. 6207 04:36:10,164 --> 04:36:11,833 FOR MANY YEARS I HAD BEEN 6208 04:36:11,833 --> 04:36:12,800 LOOKING FOR THE CURE. 6209 04:36:12,800 --> 04:36:15,770 SO WHEN I REACHED OUT TO NIH AND 6210 04:36:15,770 --> 04:36:17,405 THEY TOLD ME THESE TWO JUST 6211 04:36:17,405 --> 04:36:20,208 READING THE AMOUNT OF PAPERWORK 6212 04:36:20,208 --> 04:36:21,209 AND THINKING ABOUT WHAT MY 6213 04:36:21,209 --> 04:36:23,277 BROTHERS WOULD HAVE TO GO 6214 04:36:23,277 --> 04:36:26,681 THROUGH, LIKE MANY PLACES IN MY 6215 04:36:26,681 --> 04:36:30,051 LIFE I JUST FELT I'D LAY ON THAT 6216 04:36:30,051 --> 04:36:30,251 SWORD. 6217 04:36:30,251 --> 04:36:32,520 I FELT I DIDN'T WANT TO GO WITH 6218 04:36:32,520 --> 04:36:34,222 GRAPH VERSUS HOST. 6219 04:36:34,222 --> 04:36:36,491 THAT SCARED ME A BIT AND TAKING 6220 04:36:36,491 --> 04:36:39,093 THE RISK OF HAVING MY OWN CELLS 6221 04:36:39,093 --> 04:36:43,131 RETURNED TO ME SOUNDED BETTER. 6222 04:36:43,131 --> 04:36:47,368 FROM A CLINICAL PERSPECTIVE I 6223 04:36:47,368 --> 04:36:48,336 FELT DESPERATE FEELING LIKE ARE 6224 04:36:48,336 --> 04:36:52,507 THERE AS MANY OPTIONS IN 2018, 6225 04:36:52,507 --> 04:36:53,908 THERE WEREN'T MANY AS THERE ARE 6226 04:36:53,908 --> 04:36:57,011 NOW AND THERE WERE THERAPY I 6227 04:36:57,011 --> 04:36:57,211 TRIED. 6228 04:36:57,211 --> 04:37:03,484 I HAD DONE THE BLOOD 6229 04:37:03,484 --> 04:37:04,886 TRANSFUSIONS EVERY THREE OR FOUR 6230 04:37:04,886 --> 04:37:05,953 WEEKS AND STILL DIDN'T HAVE THE 6231 04:37:05,953 --> 04:37:09,690 QUALITY OF LIFE I CARED FOR AND 6232 04:37:09,690 --> 04:37:12,927 TOOK MY A YEAR TO PONDER HOW 6233 04:37:12,927 --> 04:37:14,595 THAT LOOKED FOR MY FAMILY. 6234 04:37:14,595 --> 04:37:15,963 THAT WAS ONE OF THE DRIVING 6235 04:37:15,963 --> 04:37:16,230 FORCES. 6236 04:37:16,230 --> 04:37:17,698 YOU MENTIONED THE SIX MONTHS TO 6237 04:37:17,698 --> 04:37:21,769 A YEAR AND HOW DOES THAT LOOK 6238 04:37:21,769 --> 04:37:22,837 FROM A PATIENT PERSPECTIVE ALSO 6239 04:37:22,837 --> 04:37:23,938 ONE OF THE THINGS I THOUGHT 6240 04:37:23,938 --> 04:37:25,239 ABOUT AS WELL AS WITH MY FAMILY, 6241 04:37:25,239 --> 04:37:27,508 HOW DOES THAT LEVEL OF CARE LOOK 6242 04:37:27,508 --> 04:37:31,579 BEFORE, DURING AND AFTER. 6243 04:37:31,579 --> 04:37:34,916 BUT AGAIN MY QUALITY OF LIFE 6244 04:37:34,916 --> 04:37:39,220 WASN'T WA I WANTED IT TO BE 6245 04:37:39,220 --> 04:37:39,820 ANYWAY SO THAT WAS A FAMILY 6246 04:37:39,820 --> 04:37:49,463 DECISION. 6247 04:37:49,463 --> 04:37:51,666 >> FOR THE SECOND PATIENT I 6248 04:37:51,666 --> 04:37:53,734 WONDER IF ENGAGING WITH A 6249 04:37:53,734 --> 04:37:54,936 PATIENT ABOUT OPTIMIZING 6250 04:37:54,936 --> 04:37:57,271 GLYCEMIC CONTROL WOULD BE THE 6251 04:37:57,271 --> 04:38:02,543 FURTHER STEP EVEN BEFORE TALKING 6252 04:38:02,543 --> 04:38:04,512 ABOUT GENE THERAPY VERSUS 6253 04:38:04,512 --> 04:38:04,812 TRANSPLANT? 6254 04:38:04,812 --> 04:38:06,214 I THINK REGARDLESS OF THE 6255 04:38:06,214 --> 04:38:08,783 DIRECTION YOU GO, I THINK 6256 04:38:08,783 --> 04:38:11,452 FIGURING OUT GLYCEMIC CONTROL 6257 04:38:11,452 --> 04:38:12,153 WOULD PROBABLY BE IMPORTANT 6258 04:38:12,153 --> 04:38:13,287 WHETHER A PATIENT HAS TO PURSUE 6259 04:38:13,287 --> 04:38:14,255 IT OR NOT. 6260 04:38:14,255 --> 04:38:16,891 I DO WONDER. 6261 04:38:16,891 --> 04:38:20,494 OBVIOUSLY PATIENTS ON 6262 04:38:20,494 --> 04:38:23,931 HYDROXYUREA AND IS IT BECAUSE OF 6263 04:38:23,931 --> 04:38:25,466 COST THEY WEREN'T ABLE TO AFFORD 6264 04:38:25,466 --> 04:38:29,303 THE NEWER THERAPIES FOR GLYCEMIC 6265 04:38:29,303 --> 04:38:30,871 CONTROL TO MORE FINE TUNE LIKE 6266 04:38:30,871 --> 04:38:32,506 THE BIO FEEDBACK AND THE PUMPS 6267 04:38:32,506 --> 04:38:42,750 AND SO FORTH. 6268 04:38:50,024 --> 04:38:52,126 >> SHE REPORTS CHALLENGE WITH 6269 04:38:52,126 --> 04:38:57,265 HER SICKLE CELL DISEASE ACTS UP 6270 04:38:57,265 --> 04:39:04,138 AND BLOOD SUGAR AND REGULATING 6271 04:39:04,138 --> 04:39:09,243 IN TIMES OF ILLNESS ARE THE 6272 04:39:09,243 --> 04:39:10,344 FEEDBACK LOOP AND WE ARE 6273 04:39:10,344 --> 04:39:12,847 INVOLVED IN THAT ASPECT OF CARE. 6274 04:39:12,847 --> 04:39:16,550 >> YET SHE IS STILL EXPERIENCING 6275 04:39:16,550 --> 04:39:18,653 HYPERGLYCEMIC EPISODES? 6276 04:39:18,653 --> 04:39:20,788 THAT'S FASCINATING. 6277 04:39:20,788 --> 04:39:26,727 YOU WONDER WHICH IS THE CHICKEN 6278 04:39:26,727 --> 04:39:31,499 AND THE EGG THEN. 6279 04:39:31,499 --> 04:39:31,732 THANKS. 6280 04:39:31,732 --> 04:39:35,369 >> THIS QUESTION IS FOR 6281 04:39:35,369 --> 04:39:35,736 COURTNEY. 6282 04:39:35,736 --> 04:39:38,239 QUESTION ABOUT THE PATIENT YOU 6283 04:39:38,239 --> 04:39:44,745 MENTIONED WITH THE INTRACRANIAL 6284 04:39:44,745 --> 04:39:45,046 HEMORRHAGE. 6285 04:39:45,046 --> 04:39:48,516 WERE THERE CHANGES THAT COULD 6286 04:39:48,516 --> 04:39:51,185 HAVE PREDICTED THAT WOULD 6287 04:39:51,185 --> 04:39:51,419 HAPPEN? 6288 04:39:51,419 --> 04:39:57,458 >> GOOD QUESTION. 6289 04:39:57,458 --> 04:39:59,860 SHE HAD 100% CHIMERISM. 6290 04:39:59,860 --> 04:40:03,664 SHE WAS HAVING SOME HEADACHES 6291 04:40:03,664 --> 04:40:06,067 AND WAS MOVING SO THERE MAY HAVE 6292 04:40:06,067 --> 04:40:07,902 BEEN MORE STRESS AND HIGH BLOOD 6293 04:40:07,902 --> 04:40:10,338 PRESSURE BUT DIDN'T PRESENT TO 6294 04:40:10,338 --> 04:40:13,541 THE NIH SO I DON'T HAVE ALL THE 6295 04:40:13,541 --> 04:40:16,644 DETAILS AT THE TIME. 6296 04:40:16,644 --> 04:40:27,154 TO SAY EVEN WITH REVERSAL OF 6297 04:40:28,122 --> 04:40:28,789 SICKLE CELL DISEASE AND SURGERY 6298 04:40:28,789 --> 04:40:29,957 WOULDN'T BE INDICATED BUT IT'S 6299 04:40:29,957 --> 04:40:34,995 IMPORTANT TO HAVE THE 6300 04:40:34,995 --> 04:40:36,897 CONVERSATIONS AND INDICATIONS 6301 04:40:36,897 --> 04:40:38,466 FOR THE SYNDROME AND WE NEED TO 6302 04:40:38,466 --> 04:40:43,971 KNOW HOW TO KEEP THE PATIENTS AS 6303 04:40:43,971 --> 04:40:46,006 SAFE AS POSSIBLE AND 6304 04:40:46,006 --> 04:40:48,542 PERITRANSPLANT AND AFTERWARDS. 6305 04:40:48,542 --> 04:40:49,977 >> I'M WONDERING EVEN LONG-TERM 6306 04:40:49,977 --> 04:40:52,213 SOME PATIENTS ESPECIALLY AFTER 6307 04:40:52,213 --> 04:40:56,784 GENE THERAPY WE DON'T HAVE PAST 6308 04:40:56,784 --> 04:41:01,689 TWO, THREE FOLLOW-UP SHOULD WE 6309 04:41:01,689 --> 04:41:02,356 CAN BE CONCERNED OF THE 6310 04:41:02,356 --> 04:41:05,292 HEMOGLOBIN DROPPED SHOULD WE 6311 04:41:05,292 --> 04:41:10,264 HAVE A LOW THRESHOLD FOR 6312 04:41:10,264 --> 04:41:14,435 PATIENTS FOR DISEASE MODIFYING 6313 04:41:14,435 --> 04:41:15,970 THERAPY RATHER THAN JUST 6314 04:41:15,970 --> 04:41:16,937 FOLLOWING AND SEE HOW THEY DO. 6315 04:41:16,937 --> 04:41:19,607 >> WE DON'T HAVE THE DATA TO 6316 04:41:19,607 --> 04:41:23,944 KNOW HOW BEST TO TREAT THEM BUT 6317 04:41:23,944 --> 04:41:28,516 SOMETHING TO THINK ABOUT. 6318 04:41:28,516 --> 04:41:31,819 >> I'M FROM BOSTON UNIVERSITY 6319 04:41:31,819 --> 04:41:32,920 AND MY QUESTION IS ABOUT THE 6320 04:41:32,920 --> 04:41:33,754 FIRST CASE. 6321 04:41:33,754 --> 04:41:37,024 AS WE ROLL OUT CLINICAL GENE 6322 04:41:37,024 --> 04:41:38,826 THERAPY ACROSS CENTERS, THERE IS 6323 04:41:38,826 --> 04:41:45,099 AND I SAY THIS AS A 6324 04:41:45,099 --> 04:41:46,167 NON-HEMATOLOGIST, THERE'S A 6325 04:41:46,167 --> 04:41:51,605 VARIABILITY IN HOW THE DATA ON 6326 04:41:51,605 --> 04:41:53,941 HOW GENE THERAPY MAY OR MAY NOT 6327 04:41:53,941 --> 04:41:56,277 BE PROTECTIVE IN PATIENTS WITH 6328 04:41:56,277 --> 04:42:00,915 PRIOR STROKES IS BEING INTER 6329 04:42:00,915 --> 04:42:01,215 INTERPRETED. 6330 04:42:01,215 --> 04:42:02,082 THE QUESTION I HAVE FOR THE 6331 04:42:02,082 --> 04:42:03,818 PANEL IS HOW WE'RE GOING TO 6332 04:42:03,818 --> 04:42:04,852 APPROACH AS A COMMUNITY 6333 04:42:04,852 --> 04:42:10,157 GATHERING DATA ON THE IMPACT OF 6334 04:42:10,157 --> 04:42:14,361 GENE THERAPY ON THE RISK OF 6335 04:42:14,361 --> 04:42:20,501 CEREBRAL VAS VASCULOPATHY AND 6336 04:42:20,501 --> 04:42:22,736 THOSE PRIOR TO GENE THERAPY IF 6337 04:42:22,736 --> 04:42:26,207 THEY WERE TO GET IT. 6338 04:42:26,207 --> 04:42:29,410 >> I'LL SPOKE FOR THE NATIONAL 6339 04:42:29,410 --> 04:42:31,479 ALLIANCE AND THE USE OF A 6340 04:42:31,479 --> 04:42:32,012 REGISTRY. 6341 04:42:32,012 --> 04:42:34,281 WE HAVE THE GRAND DAD REGISTRY 6342 04:42:34,281 --> 04:42:36,283 AT OVER 50 SITES ACROSS THE 6343 04:42:36,283 --> 04:42:37,151 COUNTRY AND THINK ANYONE GOING 6344 04:42:37,151 --> 04:42:40,821 TO THE THERAPY SHOULD BE IN SOME 6345 04:42:40,821 --> 04:42:42,790 REGISTRY AND WE NEED TO COLLECT 6346 04:42:42,790 --> 04:42:45,125 THIS DATA BECAUSE THOSE ARE 6347 04:42:45,125 --> 04:42:46,827 REALLY IMPORTANT QUESTIONS. 6348 04:42:46,827 --> 04:42:47,995 AND AT THE RECENT NATIONAL 6349 04:42:47,995 --> 04:42:53,534 ALLIANCE MEETING WE STARTED THE 6350 04:42:53,534 --> 04:42:56,670 DISCUSSION OF HAVING A CONCENSUS 6351 04:42:56,670 --> 04:43:00,674 WHO SHOULD BE THOUGHT ABOUT -- 6352 04:43:00,674 --> 04:43:03,077 CONSENSUS FOR WHO SHOULD GO 6353 04:43:03,077 --> 04:43:04,912 THROUGH THERAPY AND INITIAL 6354 04:43:04,912 --> 04:43:05,980 CONVERSATIONS AND HOPING TO 6355 04:43:05,980 --> 04:43:11,952 REGROUP AT NEXT YEAR'S MEETING 6356 04:43:11,952 --> 04:43:15,122 TO HAVE CONSENSUS HAVING THE 6357 04:43:15,122 --> 04:43:16,824 MEMBER CENTERS VOTE ON 6358 04:43:16,824 --> 04:43:17,358 RECOMMENDATIONS FOR GENE 6359 04:43:17,358 --> 04:43:20,227 THERAPY. 6360 04:43:20,227 --> 04:43:24,231 >> I THINK IT'S IMPORTANT TO 6361 04:43:24,231 --> 04:43:27,768 RECOGNIZE IT IS NOT SICKLE CELL 6362 04:43:27,768 --> 04:43:29,537 DOCTORS THAT ARE THE GATE 6363 04:43:29,537 --> 04:43:32,506 KEEPERS OF THERAPY OR 6364 04:43:32,506 --> 04:43:32,806 TRANSPLANT. 6365 04:43:32,806 --> 04:43:35,075 IT'S OUR CELLULAR COLLEAGUES WE 6366 04:43:35,075 --> 04:43:37,912 DON'T REFER OR SEE ALL THE 6367 04:43:37,912 --> 04:43:39,313 PATIENTS. 6368 04:43:39,313 --> 04:43:41,649 IT'S GOING TO MAKE IT 6369 04:43:41,649 --> 04:43:43,684 HETEROGENEOUS WHO GOES IN THE 6370 04:43:43,684 --> 04:43:46,887 FIRST COUPLE YEARS AS WE HAVE 6371 04:43:46,887 --> 04:43:47,421 CLINICAL IMPLEMENTATION. 6372 04:43:47,421 --> 04:43:53,394 I AGREE IT'S IMPORTANT TO 6373 04:43:53,394 --> 04:43:55,596 UNDERSTAND ABOUT CEREBRAL 6374 04:43:55,596 --> 04:43:56,931 VASCULOPATHY AND SHOULD HAVE 6375 04:43:56,931 --> 04:43:58,399 CENTRAL READING AND THE LEVEL OF 6376 04:43:58,399 --> 04:43:59,967 STANDARD OF CARE BECAUSE I THINK 6377 04:43:59,967 --> 04:44:03,037 WE'RE GOING TO FIND THAT SOME 6378 04:44:03,037 --> 04:44:05,506 PEOPLE GET BETTER WITH CURATIVE 6379 04:44:05,506 --> 04:44:07,408 THERAPIES OR TRANSFORMATIVE 6380 04:44:07,408 --> 04:44:09,076 THERAPIES WHEN IT COMES TO 6381 04:44:09,076 --> 04:44:10,411 CEREBRAL DISEASE AND SOME MAY 6382 04:44:10,411 --> 04:44:11,879 NOT GET BETTER IN TRYING TO 6383 04:44:11,879 --> 04:44:13,213 UNDERSTAND WHAT PREDICTS THAT 6384 04:44:13,213 --> 04:44:15,716 WOULD BE VALUABLE. 6385 04:44:15,716 --> 04:44:18,552 I AGREE IF SOMEONE HAD A PRIOR 6386 04:44:18,552 --> 04:44:21,055 STROKE AND WERE LOSING THEIR 6387 04:44:21,055 --> 04:44:23,958 AFFECT AND HEMOGLOBIN IS 6388 04:44:23,958 --> 04:44:32,299 DROPPING AND HAVING MORE 6389 04:44:32,299 --> 04:44:36,136 HOMOLYSIS THEY ARE SHOULD BE 6390 04:44:36,136 --> 04:44:37,071 BACK. 6391 04:44:37,071 --> 04:44:39,006 >> CMS IS OFFERING TO RESEARCH 6392 04:44:39,006 --> 04:44:40,307 ORGANIZATIONS FOR COLLECTING 6393 04:44:40,307 --> 04:44:41,976 OUTCOME SO THAT'S ALREADY GOING 6394 04:44:41,976 --> 04:44:43,243 TO HAPPEN. 6395 04:44:43,243 --> 04:44:49,149 AND TOE SOPHI'S POINT I WANT TO 6396 04:44:49,149 --> 04:44:51,852 BRING OUT THAT THE PRESCRIBING 6397 04:44:51,852 --> 04:44:54,588 INFORMATION SAYS 6398 04:44:54,588 --> 04:44:59,827 CONTRAINDICATIONS, NONE. 6399 04:44:59,827 --> 04:45:03,664 >> REGINA CRAWFORD, OHIO STATE 6400 04:45:03,664 --> 04:45:03,964 UNIVERSITY. 6401 04:45:03,964 --> 04:45:06,033 A QUESTION ON THE SECOND CASE 6402 04:45:06,033 --> 04:45:08,469 THE HEMOGLOBIN SC PATIENT AND MY 6403 04:45:08,469 --> 04:45:10,904 QUESTION RELATES TO AT BASELINE 6404 04:45:10,904 --> 04:45:16,477 DOES SHE HAVE ANY SEQUESTRATION 6405 04:45:16,477 --> 04:45:18,846 OR KNOWN THROMBOCYTOPENIA AND 6406 04:45:18,846 --> 04:45:21,181 DOES THAT PLAY A ROLE FOR GENE 6407 04:45:21,181 --> 04:45:26,520 THERAPY OR HAPLO OR THE 6408 04:45:26,520 --> 04:45:27,588 MYELOABLATIVE? 6409 04:45:27,588 --> 04:45:38,232 >> SHE DOESN'T HAVE AMEGALLY OR 6410 04:45:53,013 --> 04:45:54,448 CYTOPENIA AND YOU HAVE TO MAKE 6411 04:45:54,448 --> 04:46:00,120 SURE THE PATIENT DOESN'T HAVE 6412 04:46:00,120 --> 04:46:04,224 HLA ALLO IMMUNIZATION. 6413 04:46:04,224 --> 04:46:10,764 IT'S IMPORTANT UNLIKE LEUKEMIA 6414 04:46:10,764 --> 04:46:18,205 THEY HAVEN'T HAD FAILURES 6415 04:46:18,205 --> 04:46:19,139 BEFORE. 6416 04:46:19,139 --> 04:46:29,717 >> WHEN I SEE THROMBOCYTOPENIA 6417 04:46:33,187 --> 04:46:39,727 AND IT WILL TAKE CYCLES TO GET 6418 04:46:39,727 --> 04:46:43,430 ENOUGH CD. 6419 04:46:43,430 --> 04:46:43,664 6420 04:46:43,664 --> 04:46:45,132 >> I'VE WORKED WITH REGISTRIES 6421 04:46:45,132 --> 04:46:47,835 ALL MY CAREER. 6422 04:46:47,835 --> 04:46:49,536 THEY'RE EXCELLENT FOR LOOKING 6423 04:46:49,536 --> 04:46:53,440 FOR THE RARE UNUSUAL EVENTS AND 6424 04:46:53,440 --> 04:46:55,776 BECAUSE OF THE HETEROGENEITY IN 6425 04:46:55,776 --> 04:46:56,710 SELECTION CRITERIA AND 6426 04:46:56,710 --> 04:47:01,915 APPROACHES YOU WILL FIND OUT 6427 04:47:01,915 --> 04:47:04,518 FROM REGISTRY DATA INFORMATION 6428 04:47:04,518 --> 04:47:06,320 IN THE FUTURE TO HELP YOU SELECT 6429 04:47:06,320 --> 04:47:08,021 PATIENTS BETTER BUT THERE'S ONE 6430 04:47:08,021 --> 04:47:09,823 PROBLEM, REC STRIS DON'T FUND 6431 04:47:09,823 --> 04:47:11,592 RESEARCH TESTS. 6432 04:47:11,592 --> 04:47:17,598 WE CAN ONLY COLLECT DET ON TESTS 6433 04:47:17,598 --> 04:47:19,733 THAT PEOPLE GET. 6434 04:47:19,733 --> 04:47:21,568 WE DON'T TELL PEOPLE WHAT TO DO 6435 04:47:21,568 --> 04:47:23,871 BUT TELL US WHAT THEY DID BUT 6436 04:47:23,871 --> 04:47:25,973 CAN ONLY DO THINGS PAID FOR BY 6437 04:47:25,973 --> 04:47:26,840 INSURANCE. 6438 04:47:26,840 --> 04:47:27,841 ONE THING THAT WOULD HELP THE 6439 04:47:27,841 --> 04:47:30,511 FIELD WOULD BE A CLEAR STATEMENT 6440 04:47:30,511 --> 04:47:33,046 ABOUT WHAT WE CONSIDER THE 6441 04:47:33,046 --> 04:47:35,015 DIAGNOSTIC TEST TO FOLLOW 6442 04:47:35,015 --> 04:47:39,620 PATIENTS OVER TIME SO WE CAN 6443 04:47:39,620 --> 04:47:42,456 UNDERSTAND WHAT'S GOING ON IN A 6444 04:47:42,456 --> 04:47:44,491 WAY TO JUSTIFY PAYMENT BY 6445 04:47:44,491 --> 04:47:51,165 INSURANCE COMPANIES. 6446 04:47:51,165 --> 04:47:53,233 >> AND WE'RE INTERESTED IN 6447 04:47:53,233 --> 04:47:54,902 LOOKING INTO THE ONLY FOR 6448 04:47:54,902 --> 04:47:56,603 GENETIC RISK FACTORS FOR 6449 04:47:56,603 --> 04:47:59,573 LONG-TERM HEALTH EFFECTS OF 6450 04:47:59,573 --> 04:48:00,374 CURATIVE THERAPIES FOR SICKLE 6451 04:48:00,374 --> 04:48:01,308 CELL DISEASE AND FORTUNATE TO 6452 04:48:01,308 --> 04:48:02,810 HAVE CENTERS AROUND THE 6453 04:48:02,810 --> 04:48:05,479 U.S. TRANSPLANTING THE LARGEST 6454 04:48:05,479 --> 04:48:06,613 POPULATION WITH SICKLE CELL 6455 04:48:06,613 --> 04:48:09,783 DISEASE AND ONE THING WE'RE 6456 04:48:09,783 --> 04:48:14,188 INTERESTED IN IS THE CNS EFFECTS 6457 04:48:14,188 --> 04:48:20,494 AND ADULTS VERSUS CHILDREN AND 6458 04:48:20,494 --> 04:48:22,362 TRANSPLANTING THERAPIES SCO I 6459 04:48:22,362 --> 04:48:23,964 THINK IT'S IMPORTANT TO USE AS 6460 04:48:23,964 --> 04:48:26,033 PRELIMINARY DATA TO TRY TO HELP 6461 04:48:26,033 --> 04:48:28,769 WITH DEVELOPING SUGGESTS AND 6462 04:48:28,769 --> 04:48:30,003 GUIDELINES FOR PATIENTS LONG 6463 04:48:30,003 --> 04:48:35,609 TERM. 6464 04:48:35,609 --> 04:48:37,878 >> WE'LL HAVE THIS BE THE LAST 6465 04:48:37,878 --> 04:48:38,145 QUESTION. 6466 04:48:38,145 --> 04:48:39,947 >> I TIMED THAT PERFECTLY. 6467 04:48:39,947 --> 04:48:41,315 MY QUESTION IS FOR THE REAL 6468 04:48:41,315 --> 04:48:46,353 EXPERT ON THE PANEL, THE PERSON 6469 04:48:46,353 --> 04:48:54,628 WHO'S HAD THE PROCEDURE DONE. 6470 04:48:54,628 --> 04:48:56,129 WALK US THROUGH ADULT REASONING. 6471 04:48:56,129 --> 04:49:00,033 SOME ADULTS HAVE COGNITIVE 6472 04:49:00,033 --> 04:49:05,272 DYSFUNCTION, SOME DON'T. 6473 04:49:05,272 --> 04:49:08,175 THEIR ABILITY TO REASON AND USE 6474 04:49:08,175 --> 04:49:14,882 THE TERMINOLOGY TO MAKE A COGENT 6475 04:49:14,882 --> 04:49:16,483 DECISION VARIES PROBABLY BY 6476 04:49:16,483 --> 04:49:17,951 THEIR AMOUNT OF COGNITIVE 6477 04:49:17,951 --> 04:49:18,352 DYSFUNCTION. 6478 04:49:18,352 --> 04:49:19,920 HELP US AS PROVIDERS SORT THAT 6479 04:49:19,920 --> 04:49:22,990 THROUGH AS WE DEAL WITH OUR 6480 04:49:22,990 --> 04:49:25,392 PATIENTS BECAUSE WE'RE TRYING TO 6481 04:49:25,392 --> 04:49:28,061 COMMUNICATE ALL THIS COMPLICATED 6482 04:49:28,061 --> 04:49:30,030 STUFF EVEN THE DOCTORS DON'T 6483 04:49:30,030 --> 04:49:31,765 UNDERSTAND TO A PATIENT TO HELP 6484 04:49:31,765 --> 04:49:32,499 THEM MAKE DECISIONS. 6485 04:49:32,499 --> 04:49:35,135 >> THANK YOU. 6486 04:49:35,135 --> 04:49:39,873 IT IS A CONCERTED EFFORT ON THE 6487 04:49:39,873 --> 04:49:41,241 PROVIDER, THE PATIENT AND THAT 6488 04:49:41,241 --> 04:49:46,780 GROUP MUCH -- OF PEOPLE THAT IS 6489 04:49:46,780 --> 04:49:48,715 SURROUNDING THEM, THEIR 6490 04:49:48,715 --> 04:49:48,982 COMMUNITY. 6491 04:49:48,982 --> 04:49:51,551 I WOULD SAY AS YOU'RE RIGHT, I 6492 04:49:51,551 --> 04:49:53,220 SPENT SO MUCH TIME IN THE 6493 04:49:53,220 --> 04:49:55,789 HOSPITAL SOMETIMES THE MEDICAL 6494 04:49:55,789 --> 04:49:57,257 TERMINOLOGY BECAME SECOND NATURE 6495 04:49:57,257 --> 04:49:57,591 TO ME. 6496 04:49:57,591 --> 04:50:00,928 THOSE ARE PROBABLY THE SAT WORDS 6497 04:50:00,928 --> 04:50:03,330 I KNEW PRIOR IT TAKING THE SAT 6498 04:50:03,330 --> 04:50:04,798 BUT BREAKING IT DOWN AND COMING 6499 04:50:04,798 --> 04:50:10,437 FROM A HUMAN PERSPECTIVE I THINK 6500 04:50:10,437 --> 04:50:12,472 SOMETIMES PROVIDERS CAN GET SO 6501 04:50:12,472 --> 04:50:13,674 STUCK TO THE DATA AND THE 6502 04:50:13,674 --> 04:50:15,676 PROVIDER PORTION OF IT THAT THEY 6503 04:50:15,676 --> 04:50:20,247 FORGET THEY'RE TALKING TO A 6504 04:50:20,247 --> 04:50:22,816 PATIENT WITH A LIFE. 6505 04:50:22,816 --> 04:50:24,217 BEFORE BEING A SICKLE CELL 6506 04:50:24,217 --> 04:50:26,954 PATIENT I'M A CHILD, I AM A 6507 04:50:26,954 --> 04:50:30,657 DAUGHTER, I'M A WIFE, I'M A 6508 04:50:30,657 --> 04:50:31,725 BONUS MOTHER, EMPLOYEE. 6509 04:50:31,725 --> 04:50:32,993 ALL THOSE THINGS MAKE UP THE 6510 04:50:32,993 --> 04:50:36,630 PATIENT AND I THINK TAKING THAT 6511 04:50:36,630 --> 04:50:38,799 INTO CONSIDERATION WHEN YOU ARE 6512 04:50:38,799 --> 04:50:40,600 PRESENTING ALL THE OPTIONS AND 6513 04:50:40,600 --> 04:50:44,738 AGAIN IT'S ABOUT FINDING AND 6514 04:50:44,738 --> 04:50:46,039 EXPLAINING ALL THE OPTIONS 6515 04:50:46,039 --> 04:50:48,041 AVAILABLE TO THE PATIENT AND TO 6516 04:50:48,041 --> 04:50:49,643 THAT FAMILY BECAUSE THERE ARE 6517 04:50:49,643 --> 04:50:52,512 TIMES THAT YOU'RE IN SO MUCH 6518 04:50:52,512 --> 04:50:56,616 PAIN YOU'RE NOT THINKING ABOUT 6519 04:50:56,616 --> 04:50:58,051 ANYTHING ABOUT ANYTHING BUT PAIN 6520 04:50:58,051 --> 04:50:59,619 MEDICATION OR TREATMENT. 6521 04:50:59,619 --> 04:51:02,589 HAVING THAT ONE PERSON YOU CAN 6522 04:51:02,589 --> 04:51:05,225 TALK TO AS THE PROVIDER WHEN THE 6523 04:51:05,225 --> 04:51:07,094 PATIENT IS JUST NOT IN A HEAD 6524 04:51:07,094 --> 04:51:08,261 SPACE, TO TALK ABOUT THOSE 6525 04:51:08,261 --> 04:51:14,534 THINGS IS VERY HELPFUL. 6526 04:51:14,534 --> 04:51:16,303 ALSO TALKING ABOUT THE REAL 6527 04:51:16,303 --> 04:51:17,371 THINGS THAT AFFECT THEM 6528 04:51:17,371 --> 04:51:19,473 DEPENDING ON THE METHODOLOGY. 6529 04:51:19,473 --> 04:51:21,341 BEING OUT OF WORK FOR MY 6530 04:51:21,341 --> 04:51:24,044 PROVIDER, MY CAREGIVER, FOR 6531 04:51:24,044 --> 04:51:24,277 MYSELF. 6532 04:51:24,277 --> 04:51:26,246 TRANSPORTATION, FOOD, ALL THOSE 6533 04:51:26,246 --> 04:51:30,951 INSECURITIES THAT COME ALONG 6534 04:51:30,951 --> 04:51:32,619 WITH THAT PATIENT AND BEING ABLE 6535 04:51:32,619 --> 04:51:34,855 TO SIT DOWN WITH THEM. 6536 04:51:34,855 --> 04:51:39,292 THE 15-MINUTE CONVERSATION WHERE 6537 04:51:39,292 --> 04:51:42,062 YOU'RE IN THEN GONE WITH THE 6538 04:51:42,062 --> 04:51:45,098 PATIENT AND SOMETIMES IT CAN 6539 04:51:45,098 --> 04:51:46,767 FEEL LIKE YOU'RE JUST A NUMBER 6540 04:51:46,767 --> 04:51:47,834 AND WE JUST WANT TO BE HEARD. 6541 04:51:47,834 --> 04:51:51,271 WE WANT TO BE ABLE TO EXPLAIN 6542 04:51:51,271 --> 04:51:52,506 OURSELVES AND WHERE WE ARE AS AN 6543 04:51:52,506 --> 04:51:53,907 ADULT AND WHERE WE'RE TRYING TO 6544 04:51:53,907 --> 04:51:54,408 GO. 6545 04:51:54,408 --> 04:51:55,876 A QUICK STORY. 6546 04:51:55,876 --> 04:51:59,212 I WAS MARRIED AND WANTED 6547 04:51:59,212 --> 04:52:00,614 CHILDREN THOUGHT THAT BEING ON 6548 04:52:00,614 --> 04:52:02,349 ONE OF THESE THERAPIES WOULD 6549 04:52:02,349 --> 04:52:04,384 HELP ME GET TO THAT BUT GETTING 6550 04:52:04,384 --> 04:52:09,890 TO THAT TABLE AND REALIZING THIS 6551 04:52:09,890 --> 04:52:11,158 PARTICULAR TREATMENT WOULD 6552 04:52:11,158 --> 04:52:14,795 SOMEWHAT TAKE THAT ABILITY FROM 6553 04:52:14,795 --> 04:52:14,961 ME. 6554 04:52:14,961 --> 04:52:20,434 THERE WAS PRESERVATION BUT THAT 6555 04:52:20,434 --> 04:52:23,003 WAS ANOTHER TIME IN MY LIFE 6556 04:52:23,003 --> 04:52:25,772 FEELING I HAD TO GRIEF THAT. 6557 04:52:25,772 --> 04:52:26,840 SICKLE CELL HAD TAKEN SO MUCH 6558 04:52:26,840 --> 04:52:28,842 FROM ME I WANTED TO CLAIM 6559 04:52:28,842 --> 04:52:29,676 SOMETHING I WANTED. 6560 04:52:29,676 --> 04:52:37,651 SO I HAD TO GRIEVE THAT AND EVEN 6561 04:52:37,651 --> 04:52:40,253 IF IT DIDN'T WORK FOR ME AS AN 6562 04:52:40,253 --> 04:52:41,555 OPPORTUNITY THE PROVIDERS 6563 04:52:41,555 --> 04:52:44,491 SOMEONE COULD FIND OUT WHAT HAD 6564 04:52:44,491 --> 04:52:45,992 HAPPENED TO ME TO HELP 6565 04:52:45,992 --> 04:52:46,593 GENERATIONS. 6566 04:52:46,593 --> 04:52:49,029 THAT WAS MY MIND SET GOING 6567 04:52:49,029 --> 04:52:49,262 FORWARD. 6568 04:52:49,262 --> 04:52:51,832 ONCE I DECIDED TO MAKE THIS 6569 04:52:51,832 --> 04:52:56,903 DECISION, IF NOTHING ELSE WAS 6570 04:52:56,903 --> 04:52:58,705 LEARNED BUT DATA, THEN IT WAS 6571 04:52:58,705 --> 04:53:00,440 DATA THAT WOULD HELP FUTURE 6572 04:53:00,440 --> 04:53:00,907 GENERATIONS. 6573 04:53:00,907 --> 04:53:02,776 ALL OF THAT WENT TO ME MAKING 6574 04:53:02,776 --> 04:53:11,518 THE DECISION TO DO THIS. 6575 04:53:11,518 --> 04:53:12,819 >> SO THANK YOU VERY MUCH. 6576 04:53:12,819 --> 04:53:15,055 BEFORE WE END THIS SESSION WE DO 6577 04:53:15,055 --> 04:53:16,723 HAVE A QUESTION ON LINE AND SOME 6578 04:53:16,723 --> 04:53:20,494 COMMENTS ONLINE THAT I WANT TO 6579 04:53:20,494 --> 04:53:30,904 MAKE SURE GET ADDRESSED. 6580 04:53:46,253 --> 04:53:52,492 >> SO, I WANTED TO INTRODUCE 6581 04:53:52,492 --> 04:53:56,363 DR. JULIE KANTER CLOSING THE 6582 04:53:56,363 --> 04:54:01,835 SESSION WITH THE PRACTICAL 6583 04:54:01,835 --> 04:54:04,871 ASPECTS OF CLINICAL GENE THERAPY 6584 04:54:04,871 --> 04:54:05,672 PROGRAMS WITH SICKLE CELL 6585 04:54:05,672 --> 04:54:05,906 DISEASE. 6586 04:54:05,906 --> 04:54:07,974 >> SORRY I'M NOT THERE IN 6587 04:54:07,974 --> 04:54:08,241 PERSON. 6588 04:54:08,241 --> 04:54:09,142 I HAD PLANNED TO BE BUT IT 6589 04:54:09,142 --> 04:54:12,479 DOESN'T WORK OUT THAT WE. 6590 04:54:12,479 --> 04:54:13,413 -- WAY. 6591 04:54:13,413 --> 04:54:16,483 I'M HOPING I'LL BE ABLE TO 6592 04:54:16,483 --> 04:54:18,051 ANSWER QUESTIONS AND ABOUT HALF 6593 04:54:18,051 --> 04:54:19,886 THE COMMENTS IN CHAT WERE FROM 6594 04:54:19,886 --> 04:54:20,620 ME SO I'LL COVER SOME OF THOSE 6595 04:54:20,620 --> 04:54:24,491 THINGS. 6596 04:54:24,491 --> 04:54:25,992 SO I'M GOING TO TALK MORE ABOUT 6597 04:54:25,992 --> 04:54:28,495 HOW WE SET THINGS UP FOR GENE 6598 04:54:28,495 --> 04:54:28,728 THERAPY. 6599 04:54:28,728 --> 04:54:30,297 WHAT IT LOOKS LIKE AND I'LL 6600 04:54:30,297 --> 04:54:31,498 TOUCH ON SOME OF THE POINTS ON 6601 04:54:31,498 --> 04:54:33,833 THE NEED FOR A TEAM AS WE 6602 04:54:33,833 --> 04:54:35,535 APPROACH GENE THERAPY IN THE 6603 04:54:35,535 --> 04:54:35,835 REAL WORLD. 6604 04:54:35,835 --> 04:54:37,938 THESE ARE MY DISCLOSURES. 6605 04:54:37,938 --> 04:54:38,738 NEXT SLIDE. 6606 04:54:38,738 --> 04:54:39,873 SO YOU'VE HEARD ALL ABOUT THIS 6607 04:54:39,873 --> 04:54:40,140 TODAY. 6608 04:54:40,140 --> 04:54:43,276 WE DON'T REALLY NEED TO GO BACK 6609 04:54:43,276 --> 04:54:44,044 THROUGH THE PROCESS. 6610 04:54:44,044 --> 04:54:46,279 I WANT TO MAKE SURE PEOPLE 6611 04:54:46,279 --> 04:54:48,882 RECOGNIZE IS THERE'S MULTIPLE 6612 04:54:48,882 --> 04:54:50,450 POINTS IN THE PROCESS IN WHICH 6613 04:54:50,450 --> 04:54:51,885 THE PERSON LIVING WITH SICKLE 6614 04:54:51,885 --> 04:54:54,154 CELL DISEASE ARE WAITING AND 6615 04:54:54,154 --> 04:54:57,257 NICINITIATING TRANSFUSION THERA 6616 04:54:57,257 --> 04:54:59,726 AND HAVE TO STOP HYDROXYUREA AND 6617 04:54:59,726 --> 04:55:02,329 HOW TO OPTIMIZE THAT AND ONCE 6618 04:55:02,329 --> 04:55:03,463 STEM CELLS ARE COLLECTED IT 6619 04:55:03,463 --> 04:55:04,864 COULD BE SIX MONTHS UNTIL THEY 6620 04:55:04,864 --> 04:55:05,865 GET THE CELLS BACK. 6621 04:55:05,865 --> 04:55:07,534 WHO IS MANAGING THE PATIENT IS 6622 04:55:07,534 --> 04:55:10,570 KEY TO MAKING SURE WE HAVE GOOD 6623 04:55:10,570 --> 04:55:12,072 OUTCOMES FROM GENE THERAPY AND 6624 04:55:12,072 --> 04:55:14,307 LONG-TERM FOLLOW-UP, 15 YEARS IS 6625 04:55:14,307 --> 04:55:15,075 A LONG TIME. 6626 04:55:15,075 --> 04:55:16,776 WHAT'S THAT LOOK LIKE AND WHERE 6627 04:55:16,776 --> 04:55:18,245 IS THIS INDIVIDUAL GOING TO BE 6628 04:55:18,245 --> 04:55:18,511 FOLLOWED? 6629 04:55:18,511 --> 04:55:22,015 THESE ARE TRANSFORMATIVE AND NOT 6630 04:55:22,015 --> 04:55:25,819 YET CURATIVE PROCESS AND NEED TO 6631 04:55:25,819 --> 04:55:31,458 BE FOLLOWED BY SOMEONE WHO KNOWS 6632 04:55:31,458 --> 04:55:36,263 OF SICKLE CELL DISEASE. 6633 04:55:36,263 --> 04:55:40,400 WE ASKED THE QUESTION SO SAY, 6634 04:55:40,400 --> 04:55:45,739 OKAY, WE HAVE 90 CENTERS NOW 6635 04:55:45,739 --> 04:55:45,972 113. 6636 04:55:45,972 --> 04:55:49,442 THERE'S 113 SICKLE CELL CENTERS 6637 04:55:49,442 --> 04:55:52,579 GIVING MULTIDISCIPLINARY CARE. 6638 04:55:52,579 --> 04:55:53,913 WE RECOGNIZE WE'RE CARING FOR 6639 04:55:53,913 --> 04:55:57,851 THE MAJORITY OF INDIVIDUALS WITH 6640 04:55:57,851 --> 04:55:59,319 SICKLE CELL DISEASE SEEN BY 6641 04:55:59,319 --> 04:56:00,020 SPECIALISTS. 6642 04:56:00,020 --> 04:56:03,423 WE NEEDED TO BE IN THE ROOM TO 6643 04:56:03,423 --> 04:56:05,525 DISCUSS WHAT GUIDANCE IS NEEDED 6644 04:56:05,525 --> 04:56:07,394 AND HOW TO OPTIMIZE INDIVIDUALS 6645 04:56:07,394 --> 04:56:08,461 PRETREATMENT AND LONG-TERM. 6646 04:56:08,461 --> 04:56:11,331 HOW TO MAKE IT FINANCIALLY AND 6647 04:56:11,331 --> 04:56:12,999 HOLISTICALLY WORTHWHILE. 6648 04:56:12,999 --> 04:56:14,234 THEY TAKE LONGER THAN THE ONE 6649 04:56:14,234 --> 04:56:24,411 TIME TREATMENT. 6650 04:56:24,411 --> 04:56:26,579 WE RECOGNIZE THERE'S ISSUES AND 6651 04:56:26,579 --> 04:56:27,781 SPECIFICALLY IN THE PAST WE KNOW 6652 04:56:27,781 --> 04:56:30,317 THERE'S A DISCONNECT BETWEEN 6653 04:56:30,317 --> 04:56:33,653 HEMATOLOGY AND TRANSPLANT. 6654 04:56:33,653 --> 04:56:35,755 SPECIFICALLY OFTEN TRANSPLANT 6655 04:56:35,755 --> 04:56:37,190 TREATS -- NOT ALL OF YOU. 6656 04:56:37,190 --> 04:56:38,725 WE HAVE FABULOUS COLLEAGUES IN 6657 04:56:38,725 --> 04:56:40,193 THE ROOM BUT SOMETIMES THE 6658 04:56:40,193 --> 04:56:43,163 TRANSPLANT IS LIKE THE SURGEON. 6659 04:56:43,163 --> 04:56:45,065 THEY WANT TO TAKE CARE OF THE 6660 04:56:45,065 --> 04:56:47,334 PERSON AND GET THE JOB DONE AND 6661 04:56:47,334 --> 04:56:48,535 SEND THE PERSON BACK WHERE THEY 6662 04:56:48,535 --> 04:56:50,103 CAME FROM AND THERE'S NOT A 6663 04:56:50,103 --> 04:56:50,904 DISTINGUISHING POINT OF 6664 04:56:50,904 --> 04:56:52,038 TRANSITION BEFORE, DURING AND 6665 04:56:52,038 --> 04:56:52,305 AFTER. 6666 04:56:52,305 --> 04:56:55,709 THERE'S SO MUCH TIME IN BETWEEN 6667 04:56:55,709 --> 04:56:57,344 THINKING ABOUT GENE THERAPY WE 6668 04:56:57,344 --> 04:57:00,080 HAVE TO BE PREPARED TO MANAGE 6669 04:57:00,080 --> 04:57:02,949 THE PATIENTS EFFECTIVELY. 6670 04:57:02,949 --> 04:57:08,021 WE WANTED TO UNDERSTAND THE 6671 04:57:08,021 --> 04:57:12,425 BARRIERS TO TRANSFORMATIVE 6672 04:57:12,425 --> 04:57:12,692 THERAPIES. 6673 04:57:12,692 --> 04:57:14,894 WHAT IF YOU DON'T HAVE A 6674 04:57:14,894 --> 04:57:19,199 TRANSPLANT PROGRAM? 6675 04:57:19,199 --> 04:57:25,138 WE FOUND BARRIERS AS THOSE 6676 04:57:25,138 --> 04:57:26,539 LIVING WITH BARRIERS AND NEEDS 6677 04:57:26,539 --> 04:57:32,512 FOR PSYCHOLOGISTS AND MENTAL 6678 04:57:32,512 --> 04:57:33,713 HEALTH SUPPORT. 6679 04:57:33,713 --> 04:57:36,850 AND THEN THERE'S OFTEN HOSPITAL 6680 04:57:36,850 --> 04:57:37,984 ADMINISTRATIVE-BASED ISSUES WITH 6681 04:57:37,984 --> 04:57:39,152 FINANCIAL BARRIERS WHEN 6682 04:57:39,152 --> 04:57:40,487 NEGOTIATING CONTRACTS. 6683 04:57:40,487 --> 04:57:42,155 WE ALL KNOW ABOUT THE 6684 04:57:42,155 --> 04:57:43,089 LIMITATIONS OF INSURANCE. 6685 04:57:43,089 --> 04:57:46,059 WE DON'T WANT TO GET TOO FAR 6686 04:57:46,059 --> 04:57:46,659 DOWN ROAD OR WE'LL NEVER GET 6687 04:57:46,659 --> 04:57:56,736 OUT. 6688 04:58:03,843 --> 04:58:05,712 TO THE ALLIANCE WAS TO SUPPORT 6689 04:58:05,712 --> 04:58:07,714 AND PROVIDE ACCESS TO CARE. 6690 04:58:07,714 --> 04:58:10,917 IT'S OUR OPINION NO ONE SHOULD 6691 04:58:10,917 --> 04:58:11,551 HAVE SICKLE CELL DISEASE AND NOT 6692 04:58:11,551 --> 04:58:13,319 HAVE THE OPPORTUNITY TO SEE A 6693 04:58:13,319 --> 04:58:13,787 SPECIALIST. 6694 04:58:13,787 --> 04:58:17,357 THAT'S WHAT WE CAN OFFER IS 6695 04:58:17,357 --> 04:58:20,093 SUPPORT MORE SICKLE CELL DISEASE 6696 04:58:20,093 --> 04:58:22,796 CENTERS TO PROVIDE EQUITABLE 6697 04:58:22,796 --> 04:58:25,999 ACCESS TO HEALTH CARE. 6698 04:58:25,999 --> 04:58:28,635 THERE'S 113 AND YOU CAN GO HERE 6699 04:58:28,635 --> 04:58:31,938 TO SEE THE MAP. 6700 04:58:31,938 --> 04:58:34,107 WE DEVELOPED A CONSENSUS 6701 04:58:34,107 --> 04:58:34,474 PROCESS. 6702 04:58:34,474 --> 04:58:36,109 WE'RE LOOKING AREAS OF DATA IN 6703 04:58:36,109 --> 04:58:40,647 MANY AREAS. 6704 04:58:40,647 --> 04:58:44,050 WE CAN'T WAIT FOR DATA AND 6705 04:58:44,050 --> 04:58:45,084 STARTED WITH LITERATURE REVIEW 6706 04:58:45,084 --> 04:58:46,619 AND UNDERSTAND HOW THEY'RE 6707 04:58:46,619 --> 04:58:46,986 PRACTICING NOW. 6708 04:58:46,986 --> 04:58:49,689 IF IT'S TALKING ABOUT HOW OFTEN 6709 04:58:49,689 --> 04:58:51,624 YOU GET AN ECHO WHAT ARE YOU 6710 04:58:51,624 --> 04:58:54,928 DOING AND WHAT DO GUIDELINES 6711 04:58:54,928 --> 04:58:55,094 SAY. 6712 04:58:55,094 --> 04:58:58,932 WE MEET IN PERSON TO COMPROMISE 6713 04:58:58,932 --> 04:59:01,034 AND HAVE A FINAL VOTE ONE VOTE 6714 04:59:01,034 --> 04:59:11,444 PER CENTER IS PERMITTED. 6715 04:59:12,145 --> 04:59:18,084 YOU CAN SEE INDIVIDUALS WITH 6716 04:59:18,084 --> 04:59:21,454 SICKLE CELL DISEASE AND WE 6717 04:59:21,454 --> 04:59:22,322 STARTED THE DISCUSSION OF WHO 6718 04:59:22,322 --> 04:59:24,023 SHOULD GET THE THERAPIES BUT 6719 04:59:24,023 --> 04:59:28,261 THAT'S NOT UNTIL NEXT YEAR. 6720 04:59:28,261 --> 04:59:30,330 SOW WE TALKED IN BUCKETS. 6721 04:59:30,330 --> 04:59:32,031 WE SAID COMPONENTS OF 6722 04:59:32,031 --> 04:59:32,432 RECOMMENDATIONS. 6723 04:59:32,432 --> 04:59:34,334 WHO SHOULD BE AT YOUR 6724 04:59:34,334 --> 04:59:35,068 TRANSFORMATIVE CENTER AND WHO 6725 04:59:35,068 --> 04:59:36,503 NEEDS TO BE ON YOUR TEAM AND 6726 04:59:36,503 --> 04:59:37,604 WHAT PROCESSES NEED TO BE IN 6727 04:59:37,604 --> 04:59:37,871 PLACE. 6728 04:59:37,871 --> 04:59:40,940 WE NEED TO HAVE DEFINED PRE, 6729 04:59:40,940 --> 04:59:42,442 DURING AND POST CARE. 6730 04:59:42,442 --> 04:59:44,777 WHO DOES THE PATIENT CALL WHEN 6731 04:59:44,777 --> 04:59:45,845 THEY NEED SOMETHING AT THIS 6732 04:59:45,845 --> 04:59:46,746 STAGE AND WHAT PRIOR EXPERIENCE 6733 04:59:46,746 --> 04:59:48,515 IS NEEDED AND MAKING SURE THE 6734 04:59:48,515 --> 04:59:51,851 PROTOCOLS ARE IN PLACE. 6735 04:59:51,851 --> 04:59:53,987 THIS GOES FOR ALLO GENEIC 6736 04:59:53,987 --> 04:59:54,621 TRANSPLANT AS WELL. 6737 04:59:54,621 --> 04:59:57,090 WE CAME UP WITH TWO IMPORTANT 6738 04:59:57,090 --> 04:59:58,157 RECOMMENDATIONS STATEMENTS. 6739 04:59:58,157 --> 05:00:01,661 ONE IS DESPITE A DECADE OF 6740 05:00:01,661 --> 05:00:02,395 CLINICAL TRIALS WE KNOW GENE 6741 05:00:02,395 --> 05:00:05,298 THERAPIES HAS ONLY BEEN DONE IN 6742 05:00:05,298 --> 05:00:12,105 A SMALL NUMBER OF INDIVIDUALS 6743 05:00:12,105 --> 05:00:14,240 WITH FOLLOW-UP AND. 6744 05:00:14,240 --> 05:00:17,544 AND WE ALSO KNOW THE GENE 6745 05:00:17,544 --> 05:00:18,645 THERAPY NEEDS TO BE INTERESTED 6746 05:00:18,645 --> 05:00:20,480 AS TRANSFORMATIVE INSTEAD OF 6747 05:00:20,480 --> 05:00:23,049 CURATIVE AND UNTIL WE HAVE DATA 6748 05:00:23,049 --> 05:00:28,488 WE CANNOT CALL IT CURATIVE IT'S 6749 05:00:28,488 --> 05:00:31,591 NOT FAIR TO PROMISE A CURE WITH 6750 05:00:31,591 --> 05:00:33,826 WHAT HAS NOT BEEN IDENTIFIED. 6751 05:00:33,826 --> 05:00:36,095 AND TRANSPLANTATION FOR SICKLE 6752 05:00:36,095 --> 05:00:39,899 CELL DISEASE IN DISEASE 6753 05:00:39,899 --> 05:00:50,443 AUTOLOGOUS TREATMENT AND THESE 6754 05:00:52,512 --> 05:00:56,849 WERE IMPORTANT ON VOTING. 6755 05:00:56,849 --> 05:00:58,751 I SHOWED YOU THIS EARLIER AND 6756 05:00:58,751 --> 05:01:00,019 PULLED IT APART TO TALK ABOUT 6757 05:01:00,019 --> 05:01:02,255 HOW THERE ARE SEVERAL PIECES AND 6758 05:01:02,255 --> 05:01:07,694 PARTS OF WHAT'S GOING ON IN THE 6759 05:01:07,694 --> 05:01:14,634 PROCESS OF GENE THERAPY AND 6760 05:01:14,634 --> 05:01:16,936 MANAGED BY HEMATOLOGISTS AND 6761 05:01:16,936 --> 05:01:18,504 MAKE SURE THEY SEE SPECIALISTS 6762 05:01:18,504 --> 05:01:29,048 NOT JUST A TRANSPLANT SPECIALIST 6763 05:01:39,125 --> 05:01:40,493 AND THIS IS HOURS UPON HOURS AND 6764 05:01:40,493 --> 05:01:41,594 MONTHS OF CONSIDERATION. 6765 05:01:41,594 --> 05:01:44,864 IT USUALLY TAKES ME 10 TO 15 6766 05:01:44,864 --> 05:01:46,466 HOURS WITH SOMEONE, FACE TO FACE 6767 05:01:46,466 --> 05:01:48,034 BEFORE WE TALK ABOUT GOING 6768 05:01:48,034 --> 05:01:54,140 THROUGH THIS THERAPY FROM TOP TO 6769 05:01:54,140 --> 05:01:58,111 BOTTOM. 6770 05:01:58,111 --> 05:02:00,513 WE HAVE TO TALK ABOUT 6771 05:02:00,513 --> 05:02:06,152 HYDROXYUREA AND TRANSFUSIONS AN 6772 05:02:06,152 --> 05:02:08,254 INPUT FROM A MULTIDISCIPLINARY 6773 05:02:08,254 --> 05:02:11,024 TEAM AND HAD A PANEL TO AGREE ON 6774 05:02:11,024 --> 05:02:12,258 TREATMENT AND TOGETHER YOU HAVE 6775 05:02:12,258 --> 05:02:14,861 TO DISCUSS THIS IS AN INDIVIDUAL 6776 05:02:14,861 --> 05:02:17,597 WHO SHOULD UNDER GO THE THERAPY 6777 05:02:17,597 --> 05:02:19,999 THEN A CONFIRMED ELIGIBILITY TO 6778 05:02:19,999 --> 05:02:21,801 PROCEED AND MAKE SURE THEY 6779 05:02:21,801 --> 05:02:23,102 CONTINUE TO GET THE 6780 05:02:23,102 --> 05:02:24,671 MULTI-DISCIPLINARY CARE WHILE 6781 05:02:24,671 --> 05:02:24,937 ADMITTED. 6782 05:02:24,937 --> 05:02:26,406 WHEN INDIVIDUALS COME TO OUR 6783 05:02:26,406 --> 05:02:28,007 CENTER FOR GENE THERAPY THEY'RE 6784 05:02:28,007 --> 05:02:30,209 ON THE TRANSPLANT TEAM AND 6785 05:02:30,209 --> 05:02:31,277 UNDERSTAND THE TRANSPLANT 6786 05:02:31,277 --> 05:02:32,612 PHYSICIAN IS IN CHARGE AND 6787 05:02:32,612 --> 05:02:34,547 UNDERSTAND I'LL DROP BY AND SEE 6788 05:02:34,547 --> 05:02:39,519 THEM AND COMMENTING ON THEIR 6789 05:02:39,519 --> 05:02:41,921 CARE AND MANAGE THEIR OPIOIDS 6790 05:02:41,921 --> 05:02:45,525 CARE AND THE 15-YEAR FOLLOW-UP 6791 05:02:45,525 --> 05:02:47,293 SHOULD BE LED BY SICKLE CELL 6792 05:02:47,293 --> 05:02:48,828 DISEASE AND PATIENTS STILL NEED 6793 05:02:48,828 --> 05:02:51,798 EYE EXAMS AND STILL NEED MRIs 6794 05:02:51,798 --> 05:02:53,499 AND MRAs. 6795 05:02:53,499 --> 05:02:55,702 NOT BECAUSE WE BELIEVE THEY'LL 6796 05:02:55,702 --> 05:02:59,605 HAVE ANOTHER STROKE BUT 6797 05:02:59,605 --> 05:03:00,339 ENDOTHELIAL DYSFUNCTION MAY NOT 6798 05:03:00,339 --> 05:03:02,775 BE REVERSED BY THIS THERAPY. 6799 05:03:02,775 --> 05:03:05,078 WE CAME UP WITH TWO LEVEL OF 6800 05:03:05,078 --> 05:03:05,445 RECOMMENDATIONS. 6801 05:03:05,445 --> 05:03:11,284 ONE OF STANDARDS AND ONE OF 6802 05:03:11,284 --> 05:03:21,561 RECOMMENDATIONS. 6803 05:03:26,065 --> 05:03:27,066 AND WE MANAGE THE INDIVIDUAL UP 6804 05:03:27,066 --> 05:03:30,803 TO THE MOMENT THEY COME UP FOR 6805 05:03:30,803 --> 05:03:33,306 TRANSPLANT AS A SICKLE CELL 6806 05:03:33,306 --> 05:03:33,973 SPECIALIST AND DURING STEM CELL 6807 05:03:33,973 --> 05:03:36,509 COLLECTION WE DO CO-MANAGEMENT. 6808 05:03:36,509 --> 05:03:38,511 A COORDINATOR MUST BE AVAILABLE 6809 05:03:38,511 --> 05:03:40,113 OND ON THE SICKLE CELL SIDE OF 6810 05:03:40,113 --> 05:03:41,080 THINGS BECAUSE THEY'LL BE IN THE 6811 05:03:41,080 --> 05:03:44,383 CLINIC AND CENTER FOR A SOLID 6812 05:03:44,383 --> 05:03:45,318 SIX MONTHS BEFORE THEY EVER MAKE 6813 05:03:45,318 --> 05:03:47,453 IT TO TRANSPLANT. 6814 05:03:47,453 --> 05:03:48,921 THEY NEED TO BE WHERE THEY'RE 6815 05:03:48,921 --> 05:03:50,523 COMFORTABLE AND SOMEBODY WHO 6816 05:03:50,523 --> 05:03:51,824 KNOWS THE PATIENT AND 6817 05:03:51,824 --> 05:03:52,492 MULTIDISCIPLINARY MEETING FOR 6818 05:03:52,492 --> 05:03:54,127 FINALLY REVIEW TO MAKE SURE 6819 05:03:54,127 --> 05:03:55,261 PATIENTS ARE READY AND 6820 05:03:55,261 --> 05:03:57,296 EVERYTHING SOCIALLY IS ALSO 6821 05:03:57,296 --> 05:03:57,530 ALIGNED. 6822 05:03:57,530 --> 05:03:58,998 THEY HAVE A PLACE TO LIVE AND 6823 05:03:58,998 --> 05:04:00,933 FOOD AND ALL THE THINGS THAT CAN 6824 05:04:00,933 --> 05:04:01,634 BE HARD DURING A LONG PROCESS 6825 05:04:01,634 --> 05:04:07,607 LIKE THIS. 6826 05:04:07,607 --> 05:04:09,675 AGAIN I WANT YOU TO SEE THE 6827 05:04:09,675 --> 05:04:11,711 NUMBER OF SPECIALISTS THAT WERE 6828 05:04:11,711 --> 05:04:18,151 STANDARD IN ENSURING GOOD 6829 05:04:18,151 --> 05:04:19,152 OUTCOME IN THE GENE THERAPY. 6830 05:04:19,152 --> 05:04:22,021 SOCIAL WORKER DEDICATED TO 6831 05:04:22,021 --> 05:04:22,889 INDIVIDUALS UNDERGOING THE 6832 05:04:22,889 --> 05:04:26,826 THERAPY A PATIENT NAVIGATOR A 6833 05:04:26,826 --> 05:04:30,363 CHW OR NAVIGATOR OR OTHER PEOPLE 6834 05:04:30,363 --> 05:04:31,397 OR PSYCHOLOGIST. 6835 05:04:31,397 --> 05:04:35,802 I GIVE A TALK ON WHERE GENE 6836 05:04:35,802 --> 05:04:36,369 THERAPY SAVES SICKLE CELL 6837 05:04:36,369 --> 05:04:38,271 DISEASE AND ENSURING WE HAVE THE 6838 05:04:38,271 --> 05:04:39,438 RESOURCES OUR PATIENTS HAVE 6839 05:04:39,438 --> 05:04:42,742 NEEDED FOR A LONG TIME INCLUDING 6840 05:04:42,742 --> 05:04:44,744 PSYCHOLOGY AND PSYCHIATRY AND 6841 05:04:44,744 --> 05:04:46,479 IMPROVED SOCIAL WORK AND PATIENT 6842 05:04:46,479 --> 05:04:48,347 NAVIGATION THAT LIVES WITHIN THE 6843 05:04:48,347 --> 05:04:55,621 SICKLE CELL CENTER. 6844 05:04:55,621 --> 05:04:57,490 YOU HAVE TO HAVE BLOOD BANK 6845 05:04:57,490 --> 05:05:02,795 EXPERIENCE AND THE KNOWLEDGE AND 6846 05:05:02,795 --> 05:05:10,570 ABILITY TO DO APHERESIS AND 6847 05:05:10,570 --> 05:05:13,039 TREAT PAIN AND THE ABILITY TO 6848 05:05:13,039 --> 05:05:16,943 FOLLOW PATIENTS 15 YEARS. 6849 05:05:16,943 --> 05:05:20,112 FACILITY RESOURCES, MOST GO 6850 05:05:20,112 --> 05:05:20,913 WITHOUT QUESTION HOWEVER, YOU'D 6851 05:05:20,913 --> 05:05:22,381 BE SURPRISED THE NUMBER OF 6852 05:05:22,381 --> 05:05:25,284 PLACES DON'T HAVE THE ABILITY TO 6853 05:05:25,284 --> 05:05:27,887 DO IN-HOUSE HEMOGLOBIN 6854 05:05:27,887 --> 05:05:30,923 QUANTIFICATION THAT CAN MAKE 6855 05:05:30,923 --> 05:05:32,491 REAL TIME TRANSFUSIONS MORE 6856 05:05:32,491 --> 05:05:33,793 DIFFICULT AND AS WE GET TO THE 6857 05:05:33,793 --> 05:05:36,329 REAL WORLD WE HAVE TO FOLLOW ALL 6858 05:05:36,329 --> 05:05:38,531 THE RULES DURING THE TREATMENT 6859 05:05:38,531 --> 05:05:39,932 IN THE GENE THERAPY TRIALS. 6860 05:05:39,932 --> 05:05:42,535 JUST BECAUSE YOU'RE NOW IN THE 6861 05:05:42,535 --> 05:05:44,470 REAL WORLD DOESN'T MEAN YOU 6862 05:05:44,470 --> 05:05:47,940 DON'T HAVE APHERESIS TO GET IT 6863 05:05:47,940 --> 05:05:48,808 LOW AS POSSIBLE PRIOR TO STEM 6864 05:05:48,808 --> 05:05:50,743 CELL COLLECTION. 6865 05:05:50,743 --> 05:05:54,180 WE ALSO WANT TO ENSURE 6866 05:05:54,180 --> 05:05:55,147 INDIVIDUALS HAVE APPROPRIATE 6867 05:05:55,147 --> 05:05:58,851 EQUITABLE AND ETHICAL ACCESS TO 6868 05:05:58,851 --> 05:06:01,320 SPERM BANKING, OVARIAN AND EGG 6869 05:06:01,320 --> 05:06:02,855 COLLECTION AND HOUSING FOR 6870 05:06:02,855 --> 05:06:04,490 NON-LOCAL PATIENTS WHO WILL COME 6871 05:06:04,490 --> 05:06:06,759 TO YOUR CENTER. 6872 05:06:06,759 --> 05:06:08,527 THEN WE STARTED TALKING ABOUT 6873 05:06:08,527 --> 05:06:10,596 THE SPECIALIZED LONG-TERM 6874 05:06:10,596 --> 05:06:11,797 FOLLOW-UP THAT'S ALSO KEY AND 6875 05:06:11,797 --> 05:06:13,332 IMPORTANT MAKING SURE WE HAVE 6876 05:06:13,332 --> 05:06:15,701 THOSE PEOPLE IN PLACE IN A 6877 05:06:15,701 --> 05:06:18,104 TRANSFORMATIVE CARE CLINIC TO 6878 05:06:18,104 --> 05:06:18,804 SEE THE SICKLE CELL AND 6879 05:06:18,804 --> 05:06:19,572 TRANSPLANT SPECIALIST. 6880 05:06:19,572 --> 05:06:22,508 TO MAKE SURE THEY CONTINUE TO 6881 05:06:22,508 --> 05:06:24,210 FOLLOW UP EVEN AFTER THE INITIAL 6882 05:06:24,210 --> 05:06:26,212 PERIOD AND THEIR PAIN MEDICINE 6883 05:06:26,212 --> 05:06:28,581 TO ENSURE THEY'RE STILL BEING 6884 05:06:28,581 --> 05:06:29,916 SCREENED FOR ALL THE POTENTIAL 6885 05:06:29,916 --> 05:06:30,883 SICKLE CELL DISEASE RELATED 6886 05:06:30,883 --> 05:06:31,784 ISSUES THAT MAY STILL HAPPEN 6887 05:06:31,784 --> 05:06:33,386 BECAUSE WE DON'T HAVE THE DATA 6888 05:06:33,386 --> 05:06:33,552 YET. 6889 05:06:33,552 --> 05:06:35,421 WE NEED TO WORK ON OUR MENTAL 6890 05:06:35,421 --> 05:06:35,855 HEALTH GAME. 6891 05:06:35,855 --> 05:06:38,324 WE DON'T KNOW YET HOW TO 6892 05:06:38,324 --> 05:06:40,493 OPTIMIZE THE MENTAL HEALTH 6893 05:06:40,493 --> 05:06:41,560 PREPARATION AND TREATMENT DURING 6894 05:06:41,560 --> 05:06:42,862 THIS PROCESS FOR INDIVIDUALS 6895 05:06:42,862 --> 05:06:44,030 LIVING WITH SICKLE CELL DISEASE. 6896 05:06:44,030 --> 05:06:45,765 I HAVE NO DOUBT THOSE 6897 05:06:45,765 --> 05:06:48,534 INDIVIDUALS WHO ALREADY 6898 05:06:48,534 --> 05:06:50,736 INDIVIDUALS WHO RECEIVED THE 6899 05:06:50,736 --> 05:06:51,771 TREATMENT WILL HELP TEACH US AND 6900 05:06:51,771 --> 05:06:56,108 CRAFT THIS FOR FUTURE PATIENTS. 6901 05:06:56,108 --> 05:06:57,243 SO WE DO BELIEVE GENE THERAPY 6902 05:06:57,243 --> 05:07:00,212 CAN IMPROVE CARE FOR EVERYONE 6903 05:07:00,212 --> 05:07:02,481 LIVING WITH SICKLE CELL DISEASE 6904 05:07:02,481 --> 05:07:03,316 AND MOST PEOPLE WON'T GET GENE 6905 05:07:03,316 --> 05:07:05,217 THERAPY FOR THE NEXT FEW YEARS. 6906 05:07:05,217 --> 05:07:07,353 SO ANYONE REFERRED BE REFERRED 6907 05:07:07,353 --> 05:07:08,220 TO SEE A SICKLE CELL DISEASE 6908 05:07:08,220 --> 05:07:08,521 SPECIALIST. 6909 05:07:08,521 --> 05:07:10,022 THAT SHOULD BE THE FIRST PERSON 6910 05:07:10,022 --> 05:07:12,091 THEY MEET TO TALK ABOUT THE 6911 05:07:12,091 --> 05:07:15,227 VARIOUS OPTIONS AND THEN THE 6912 05:07:15,227 --> 05:07:15,962 TRANSPLANT PHYSICIAN. 6913 05:07:15,962 --> 05:07:16,963 SICKLE CELL DISEASE CENTERS NEED 6914 05:07:16,963 --> 05:07:19,165 STAFFING AND CARE COORDINATOR, 6915 05:07:19,165 --> 05:07:21,100 PSYCHOLOGIST, SOCIAL WORKER, 6916 05:07:21,100 --> 05:07:23,502 ACCESS TO PSYCHIATRY AND THIS 6917 05:07:23,502 --> 05:07:26,806 WILL INCREASE INTEREST FROM 6918 05:07:26,806 --> 05:07:28,507 OTHER INTERDISCIPLINARY TEAM 6919 05:07:28,507 --> 05:07:29,575 MEMBERS. 6920 05:07:29,575 --> 05:07:31,377 SUDDENLY WE'RE THE SHINY NEW TOY 6921 05:07:31,377 --> 05:07:33,279 IN THE ROOM AND IMPROVE THIS FOR 6922 05:07:33,279 --> 05:07:34,513 PEOPLE WITH SICKLE CELL DISEASE 6923 05:07:34,513 --> 05:07:35,614 AND NOT JUST GENE THERAPY. 6924 05:07:35,614 --> 05:07:38,284 AND OF COURSE WE'LL FINALLY 6925 05:07:38,284 --> 05:07:39,251 COLLECT LONGITUDINAL DATA ON 6926 05:07:39,251 --> 05:07:40,519 PEOPLE LIVING WITH SECRETARY OF 6927 05:07:40,519 --> 05:07:40,786 DEFENSE. 6928 05:07:40,786 --> 05:07:42,221 IT'S SO IMPORTANT THIS DATA 6929 05:07:42,221 --> 05:07:44,256 INCLUDES PRE AND POST NOT JUST 6930 05:07:44,256 --> 05:07:45,791 POST DATA ON WHO HAS RECEIVED 6931 05:07:45,791 --> 05:07:47,159 THE DIFFERENT THERAPIES. 6932 05:07:47,159 --> 05:07:49,695 WE NEED A REGISTRY SUCH AS GRAND 6933 05:07:49,695 --> 05:07:51,564 DAD THE NATIONAL REGISTRY OVER 6934 05:07:51,564 --> 05:07:54,533 50 CENTERS SOON TO BE 60 TO MAKE 6935 05:07:54,533 --> 05:07:57,069 SURE WE INCLUDE ACTUAL CHART 6936 05:07:57,069 --> 05:07:58,838 REVIEWED DATA COLLECTED TO 6937 05:07:58,838 --> 05:07:59,672 COMPARE PATIENTS WHO DO AND 6938 05:07:59,672 --> 05:08:01,874 DON'T GET THE THERAPY AND THOSE 6939 05:08:01,874 --> 05:08:05,711 INDIVIDUALS ON STANDARD OF CARE. 6940 05:08:05,711 --> 05:08:07,013 WE ALSO NEED THIS BECAUSE WHAT'S 6941 05:08:07,013 --> 05:08:08,180 HAPPENED IN THE PAST WHEN YOU 6942 05:08:08,180 --> 05:08:09,415 HAVE A GRANT OR PROJECT, THAT 6943 05:08:09,415 --> 05:08:10,349 DATA GOES AWAY. 6944 05:08:10,349 --> 05:08:12,585 IT DISAPPEARS WITH THE PROJECT. 6945 05:08:12,585 --> 05:08:17,089 BUT IF YOU EMBEDDED WITHIN AN 6946 05:08:17,089 --> 05:08:18,524 ALREADY PRESENT REGISTRY IT WILL 6947 05:08:18,524 --> 05:08:23,129 CONTINUE TO COLLECT AND TELL US 6948 05:08:23,129 --> 05:08:25,631 THE DATA WE NEED TO KNOW WE LOST 6949 05:08:25,631 --> 05:08:34,340 OVER THE LAST 50 YEARS. 6950 05:08:34,340 --> 05:08:35,641 SO YOU HAVE YOUR WHOLE TEAM AND 6951 05:08:35,641 --> 05:08:36,509 EVERYBODY IN THE ROOM AND NOW 6952 05:08:36,509 --> 05:08:42,181 YOU DO THE PAPERWORK. 6953 05:08:42,181 --> 05:08:47,453 THERE'S AT LEAST FOUR TO EIGHT 6954 05:08:47,453 --> 05:08:48,954 CONTRACTS AND WHETHER YOU'RE A 6955 05:08:48,954 --> 05:08:49,522 QUALIFIED OR AUTHORIZED 6956 05:08:49,522 --> 05:08:50,456 TREATMENT CENTER. 6957 05:08:50,456 --> 05:08:53,092 I HAVE THEM ALL LISTED. 6958 05:08:53,092 --> 05:08:57,363 YOU NEED TO BE AWARE TO FOCUS ON 6959 05:08:57,363 --> 05:08:59,165 WHO WILL ENSURE THEY'LL HAPPEN 6960 05:08:59,165 --> 05:09:01,167 AND TAKE CONTRACTS FROM POINT A 6961 05:09:01,167 --> 05:09:02,768 TO B. 6962 05:09:02,768 --> 05:09:04,437 WE KNOW HOW DIFFICULT SPONSORED 6963 05:09:04,437 --> 05:09:06,038 PROJECTS CAN BE. 6964 05:09:06,038 --> 05:09:07,540 WAIT UNTIL IT'S REAL WORLD AND 6965 05:09:07,540 --> 05:09:08,908 YOU HAVE TO MAKE IT THROUGH ALL 6966 05:09:08,908 --> 05:09:11,644 THE DIFFERENT STEPS TO GET 6967 05:09:11,644 --> 05:09:11,911 APPROVALS. 6968 05:09:11,911 --> 05:09:13,012 FIGURE OUT WHO WILL SIGN THE 6969 05:09:13,012 --> 05:09:15,881 CONTRACT AND WHO WILL REVIEW THE 6970 05:09:15,881 --> 05:09:17,850 CONTRACT AND DO YOU HAVE A ROLE? 6971 05:09:17,850 --> 05:09:19,985 I DON'T GET TO SIGN THEM AT MY 6972 05:09:19,985 --> 05:09:21,353 INSTITUTION BUT MY ROLE IS TO 6973 05:09:21,353 --> 05:09:24,056 MAKE SURE THEY KEEP MOVING FROM 6974 05:09:24,056 --> 05:09:26,692 POINT A TO B AND C AND SOMETIMES 6975 05:09:26,692 --> 05:09:30,996 BACK TO A AND CDAs, TERMS OF 6976 05:09:30,996 --> 05:09:36,268 ENGAGEMENT, QUALITY ARGUMENTS 6977 05:09:36,268 --> 05:09:38,871 AND I.T. AGREEMENTS. 6978 05:09:38,871 --> 05:09:41,040 THERE'S MULTIPLE PROCESSES THAT 6979 05:09:41,040 --> 05:09:43,309 HAVE TO BE EVALUATED AND YOU 6980 05:09:43,309 --> 05:09:48,347 STILL HAVE TO GO THROUGH A 6981 05:09:48,347 --> 05:09:51,750 QUALITY EVALUATION AND APHERESIS 6982 05:09:51,750 --> 05:09:53,419 LABS HAVE TO GO THROUGH THIS AND 6983 05:09:53,419 --> 05:10:02,328 WHAT'S YOUR ROLE IN THE PROCESS. 6984 05:10:02,328 --> 05:10:03,462 WE ALSO DISCUSSED WHAT IF 6985 05:10:03,462 --> 05:10:04,830 THERE'S GAP ANALYSIS THAT 6986 05:10:04,830 --> 05:10:06,165 RECOGNIZES A PROBLEM? 6987 05:10:06,165 --> 05:10:08,734 WHO WILL MAKE SURE THE PROBLEM 6988 05:10:08,734 --> 05:10:11,871 GETS FIXED TO MOVE THINGS ALONG. 6989 05:10:11,871 --> 05:10:14,106 YOU'LL DO A TEST RUN TO MOVE IT 6990 05:10:14,106 --> 05:10:15,441 FROM PLACE TO PLACE WHERE IT 6991 05:10:15,441 --> 05:10:17,009 NEEDS TO BE. 6992 05:10:17,009 --> 05:10:18,144 ENGAGEMENT. 6993 05:10:18,144 --> 05:10:20,179 MANY CENTERS WILL REQUIRE 6994 05:10:20,179 --> 05:10:22,448 ENGAGEMENT AND A PLAN FROM YOUR 6995 05:10:22,448 --> 05:10:24,016 PAYERS BEFORE THEY'LL EVEN ALLOW 6996 05:10:24,016 --> 05:10:25,784 YOU TO BECOME A QUALIFIED 6997 05:10:25,784 --> 05:10:26,318 TREATMENT CENTER. 6998 05:10:26,318 --> 05:10:28,521 I RECOMMEND YOU TRY IT AVOID 6999 05:10:28,521 --> 05:10:29,889 THAT IF POSSIBLE AND THERE'S 7000 05:10:29,889 --> 05:10:31,590 MORE DETAILS I CAN EXPLAIN BUT 7001 05:10:31,590 --> 05:10:37,596 ME -- THE MAIN THING IS TO BE A 7002 05:10:37,596 --> 05:10:39,365 TREATMENT CENTER THEY WANT A 7003 05:10:39,365 --> 05:10:42,101 PAYER AND WE NEED TO MAKE SURE 7004 05:10:42,101 --> 05:10:43,402 THIS DOESN'T BECOME CIRCULAR AND 7005 05:10:43,402 --> 05:10:45,571 YOU NEVER GET APPROVE TO THREE 7006 05:10:45,571 --> 05:10:47,573 THE THERAPIES. 7007 05:10:47,573 --> 05:10:50,910 SO THERE'S SEVERAL PARTS TO THE 7008 05:10:50,910 --> 05:10:51,243 REIMBURSEMENT. 7009 05:10:51,243 --> 05:10:53,712 EVERYBODY HEARS THE $1.2 MILLION 7010 05:10:53,712 --> 05:10:55,381 AND FORGET YOU HAVE TO COLLECT 7011 05:10:55,381 --> 05:10:57,416 IT AND DO THE FERTILITY 7012 05:10:57,416 --> 05:10:59,952 PRESERVATION AND DO THE 7013 05:10:59,952 --> 05:11:00,486 TRANSPLANT. 7014 05:11:00,486 --> 05:11:02,354 SO MAKING SURE THEY'RE ALL 7015 05:11:02,354 --> 05:11:04,990 ALIGNED AND THE PEOPLE 7016 05:11:04,990 --> 05:11:06,258 NEGOTIATING THE PEOPLE KNOW 7017 05:11:06,258 --> 05:11:07,560 ABOUT WHAT THEY'RE NEGOTIATING 7018 05:11:07,560 --> 05:11:08,527 FOR AND YOU HAVE THE 7019 05:11:08,527 --> 05:11:14,233 COORDINATION IN PLACE. 7020 05:11:14,233 --> 05:11:16,268 IN SUMMARY GENE THERAPY IS A 7021 05:11:16,268 --> 05:11:17,436 ONE-TIME PROCESS THAT REQUIRES 7022 05:11:17,436 --> 05:11:18,804 SIGNIFICANT TIME AND DEDICATION. 7023 05:11:18,804 --> 05:11:21,140 THIS A TEAM EFFORT AND HAS TO 7024 05:11:21,140 --> 05:11:24,243 INCLUDE THE SICKLE CELL DISEASE 7025 05:11:24,243 --> 05:11:24,577 SPECIALIST. 7026 05:11:24,577 --> 05:11:25,678 THE ALLIANCE IS DEVELOPED 7027 05:11:25,678 --> 05:11:27,012 RECOMMENDATIONS TO ENSURE YOU 7028 05:11:27,012 --> 05:11:28,514 HAVE THE RIGHT PEOPLE AND 7029 05:11:28,514 --> 05:11:29,548 PROCESSES IN PLACE. 7030 05:11:29,548 --> 05:11:32,051 THIS WILL HELP ENSURE YOU HAVE A 7031 05:11:32,051 --> 05:11:35,988 COORDINATOR E OR DEDICATED TO T 7032 05:11:35,988 --> 05:11:37,189 INDIVIDUALS AND PSYCHOLOGISTS 7033 05:11:37,189 --> 05:11:39,858 AND MENTAL HEALTH CARE FOR 7034 05:11:39,858 --> 05:11:41,827 INDIVIDUALS GOING THROUGH THESE 7035 05:11:41,827 --> 05:11:42,127 PROCEDURES. 7036 05:11:42,127 --> 05:11:43,596 THE PAPERWORK AN C SUITE 7037 05:11:43,596 --> 05:11:45,164 ENGAGEMENT I CAN TELL YOU MORE 7038 05:11:45,164 --> 05:11:49,835 BUT YOU'D BE ASLEEP AND IT'S NOT 7039 05:11:49,835 --> 05:11:51,770 THAT FUN HOWEVER, IT TAKES 7040 05:11:51,770 --> 05:11:53,305 SOMEBODY TO SHEPHERD IT ALL THE 7041 05:11:53,305 --> 05:11:55,274 WAY THROUGH AND KNOW WE CAN GET 7042 05:11:55,274 --> 05:12:02,615 OUR PATIENTS TO THE 7043 05:12:02,615 --> 05:12:03,549 TRANSFORMATIVE CARE THEY 7044 05:12:03,549 --> 05:12:04,149 DESERVE. 7045 05:12:04,149 --> 05:12:04,650 THAT SHOULD BE IT. 7046 05:12:04,650 --> 05:12:06,085 I THINK WE HAVE A FEW MINUTES 7047 05:12:06,085 --> 05:12:07,720 FOR QUESTIONS. 7048 05:12:07,720 --> 05:12:10,289 THANK YOU AGAIN AND AGAIN, SORRY 7049 05:12:10,289 --> 05:12:20,699 I'M NOT THERE IN PERSON. 7050 05:12:40,252 --> 05:12:43,922 >> IN YOU DISCUSS THE OPTIMIZED 7051 05:12:43,922 --> 05:12:46,692 POINT LINE OF GENE THERAPY IN 7052 05:12:46,692 --> 05:12:47,293 THE USA? 7053 05:12:47,293 --> 05:12:50,229 IT DEPENDS ON WHAT YOU MEAN BY 7054 05:12:50,229 --> 05:12:51,930 PIPELINE AND I'LL PUT MY E-MAIL 7055 05:12:51,930 --> 05:12:54,867 IN THE DISCUSSION AND IT DEPENDS 7056 05:12:54,867 --> 05:12:56,101 IF YOU INCLUDE COMMERCIAL 7057 05:12:56,101 --> 05:12:57,403 THERAPY AT YOUR SITE VERSUS THE 7058 05:12:57,403 --> 05:13:05,978 PROCESS AND PIPELINE. 7059 05:13:05,978 --> 05:13:07,579 >> DR. FEIN. 7060 05:13:07,579 --> 05:13:12,618 >> JULIA, THAT WAS GREAT SORRY I 7061 05:13:12,618 --> 05:13:14,053 MISSED THE LAST MEETING BUT I 7062 05:13:14,053 --> 05:13:19,458 FEEL CAUGHT UP AND AS A 7063 05:13:19,458 --> 05:13:25,431 CARDIOLOGIST AND PULL MOB -- 7064 05:13:25,431 --> 05:13:28,167 PULMONOLOGIST MANAGING SICKLE 7065 05:13:28,167 --> 05:13:29,501 CELL DISEASE WHAT IS THE 7066 05:13:29,501 --> 05:13:31,136 APPROPRIATE PRE GENE THERAPY 7067 05:13:31,136 --> 05:13:32,438 EVALUATION FOR OUR PATIENTS AND 7068 05:13:32,438 --> 05:13:38,410 I WOULD BE HAPPY TO HELP WITH 7069 05:13:38,410 --> 05:13:39,945 THAT PROCESS AS WE MOVE TOWARDS 7070 05:13:39,945 --> 05:13:45,017 THAT BECAUSE I GET CONCERNED 7071 05:13:45,017 --> 05:13:47,186 WHEN THERE'S TOO MUCH HAND 7072 05:13:47,186 --> 05:13:50,089 WAVING GOING ON HOW TO PROPERLY 7073 05:13:50,089 --> 05:13:51,423 EVALUATE OUR PATIENTS. 7074 05:13:51,423 --> 05:13:53,959 >> THIS IS FROM THE 2023 MEETING 7075 05:13:53,959 --> 05:13:55,227 AN NOT THE MOST RECENT. 7076 05:13:55,227 --> 05:13:57,096 SO YOU HAVE MORE TO CATCH UP ON 7077 05:13:57,096 --> 05:13:59,031 BUT WE'LL BE HAPPY TO TALK TO 7078 05:13:59,031 --> 05:14:01,233 YOU ABOUT THAT MORE TOMORROW OR 7079 05:14:01,233 --> 05:14:01,500 WEDNESDAY. 7080 05:14:01,500 --> 05:14:04,803 THE OTHER PART WE DID START 7081 05:14:04,803 --> 05:14:06,672 TALKING ABOUT THIS YEAR IS 7082 05:14:06,672 --> 05:14:07,439 IDENTIFYING THE RIGHT PATIENT 7083 05:14:07,439 --> 05:14:10,175 AND THE BEGINNING OF THIS 7084 05:14:10,175 --> 05:14:11,643 QUESTION OR THE BEGINNING LED TO 7085 05:14:11,643 --> 05:14:14,046 AN INTERESTING IDEA OF A 7086 05:14:14,046 --> 05:14:16,348 SIX-MONTH OPTIMIZATION PERIOD. 7087 05:14:16,348 --> 05:14:17,649 HOW CAN WE OPTIMIZE INDIVIDUALS 7088 05:14:17,649 --> 05:14:19,685 TO GET THE BEST OUTCOMES FROM 7089 05:14:19,685 --> 05:14:20,586 THE THERAPIES AND WE'D LOVE TO 7090 05:14:20,586 --> 05:14:29,862 HAVE YOU ON BOARD FOR THAT. 7091 05:14:29,862 --> 05:14:31,296 >> GREG KATO. 7092 05:14:31,296 --> 05:14:34,933 THANK YOU FOR THE TALK AND 7093 05:14:34,933 --> 05:14:36,368 EDUCATING US ON THE BUREAUCRATIC 7094 05:14:36,368 --> 05:14:42,875 PROCESS TO GET THINGS SET UP. 7095 05:14:42,875 --> 05:14:53,318 CAN YOU TELL US ABOUT THE 7096 05:14:55,020 --> 05:14:57,756 COMPLEXITIES ABOUT DEPARTMENTAL 7097 05:14:57,756 --> 05:14:58,390 STAKEHOLDERS. 7098 05:14:58,390 --> 05:15:00,392 >> GREAT QUESTION. 7099 05:15:00,392 --> 05:15:04,997 THERE'S ALWAYS COMPLEXITIES AND 7100 05:15:04,997 --> 05:15:06,565 POLITICAL MANEUVERING. 7101 05:15:06,565 --> 05:15:13,972 WHEN I CAME TO UAB I SET US UP 7102 05:15:13,972 --> 05:15:15,307 OUTSIDE THE CANCER CENTER TO 7103 05:15:15,307 --> 05:15:18,243 WORK MORE INDEPENDENTLY BUT IT'S 7104 05:15:18,243 --> 05:15:21,880 A JOINT EFFORT AND I PARTNERED 7105 05:15:21,880 --> 05:15:23,849 WITH OUR TRANSPLANT PERFORM 7106 05:15:23,849 --> 05:15:25,684 WITHIN THE CANCER CENTER. 7107 05:15:25,684 --> 05:15:27,085 THAT'S DIFFERENT FROM AN 7108 05:15:27,085 --> 05:15:27,753 ACADEMIC STANDPOINT. 7109 05:15:27,753 --> 05:15:29,188 IN ACADEMIC STANDPOINT UNDER THE 7110 05:15:29,188 --> 05:15:32,958 DEPARTMENT OF MEDICINE BUT IN 7111 05:15:32,958 --> 05:15:34,560 THE HOSPITAL WE LIVE UNDER THE 7112 05:15:34,560 --> 05:15:35,527 CANCER SERVICE LINE. 7113 05:15:35,527 --> 05:15:36,495 YOU HAVE TO HAVE ALL THE 7114 05:15:36,495 --> 05:15:39,865 DIFFERENT PEOPLE ON BOARD AND 7115 05:15:39,865 --> 05:15:42,701 EVERYONE KNOWS THEIR ROLE AND 7116 05:15:42,701 --> 05:15:44,169 RRE 7117 05:15:44,169 --> 05:15:45,637 PREDEFINE IT UP FRONT AND NOT A 7118 05:15:45,637 --> 05:15:48,240 QUESTION OF WHO IS SUPPOSED TO 7119 05:15:48,240 --> 05:15:52,911 DO WHAT. 7120 05:15:52,911 --> 05:15:56,582 >> I ENJOYED THE COMMENT ABOUT 7121 05:15:56,582 --> 05:15:58,383 PATIENTS TALKING ABOUT OTHER 7122 05:15:58,383 --> 05:15:58,951 THERAPIES. 7123 05:15:58,951 --> 05:16:00,486 ARE YOU SEEING INTEREST IN ORAL 7124 05:16:00,486 --> 05:16:01,053 THERAPIES STILL IN CLINICAL 7125 05:16:01,053 --> 05:16:03,922 DEVELOPMENT? 7126 05:16:03,922 --> 05:16:05,357 >> WE SEE TREMENDOUS INTEREST IN 7127 05:16:05,357 --> 05:16:08,994 ALL THERAPIES. 7128 05:16:08,994 --> 05:16:11,597 IN ALABAMA IN THE LAST 18 MONTHS 7129 05:16:11,597 --> 05:16:14,233 WE HAD 190 NEW PATIENTS COMING 7130 05:16:14,233 --> 05:16:16,869 TO OUR CENTER, ONLY ADULTS, WITH 7131 05:16:16,869 --> 05:16:17,669 SICKLE CELL DISEASE. 7132 05:16:17,669 --> 05:16:19,204 THE MAJORITY OF THESE WERE 7133 05:16:19,204 --> 05:16:23,475 PREVIOUSLY UNAFFILIATED MEANING 7134 05:16:23,475 --> 05:16:26,211 THEY'D NEVER SEEN A SICKLE CELL 7135 05:16:26,211 --> 05:16:28,380 SPECIALIST IN THE LAST TWO YEARS 7136 05:16:28,380 --> 05:16:29,548 AND MANY DIDN'T UNDERSTAND WHY 7137 05:16:29,548 --> 05:16:33,485 ANYBODY WOULD TAKE HYDROXYUREA 7138 05:16:33,485 --> 05:16:35,320 AND HAVE INTEREST IN OTHER 7139 05:16:35,320 --> 05:16:36,522 THERAPIES AND THE BENEFIT IS 7140 05:16:36,522 --> 05:16:38,223 GETTING THEM TO WALK IN THE 7141 05:16:38,223 --> 05:16:38,557 DOOR. 7142 05:16:38,557 --> 05:16:40,425 NOW THEY CAN ASK ABOUT OTHER 7143 05:16:40,425 --> 05:16:40,692 THERAPIES. 7144 05:16:40,692 --> 05:16:43,362 THE LAST WOMAN WHO CAME IN IS A 7145 05:16:43,362 --> 05:16:45,564 41-YEAR-OLD WOMAN WITH A HISTORY 7146 05:16:45,564 --> 05:16:49,568 OF THREE STROKES AND PULMONARY 7147 05:16:49,568 --> 05:16:50,802 HYPERTENSION AND WAS NOT ON 7148 05:16:50,802 --> 05:16:52,638 CHRONIC TRANSFUSION THERAPY. 7149 05:16:52,638 --> 05:16:54,573 OBVIOUSLY THERAPY IS NOT RIGHT 7150 05:16:54,573 --> 05:16:56,775 FOR HER BUT GETTING HER TO THE 7151 05:16:56,775 --> 05:16:57,976 RIGHT SPECIALIZED THERAPY SO 7152 05:16:57,976 --> 05:17:00,279 HELP HER IMPROVE IS AND THERE'S 7153 05:17:00,279 --> 05:17:01,046 GREAT OPPORTUNITY. 7154 05:17:01,046 --> 05:17:04,016 BY NO MEANS SHOULD WE COUNT THE 7155 05:17:04,016 --> 05:17:05,050 IMPORTANCE OF NEW THERAPEUTICS. 7156 05:17:05,050 --> 05:17:07,886 IT WILL BE A LONG TIME UNTIL 7157 05:17:07,886 --> 05:17:10,556 EVERYBODY CAN GET THE THERAPY. 7158 05:17:10,556 --> 05:17:14,760 >> ANY OTHER QUESTIONS? 7159 05:17:14,760 --> 05:17:16,361 THANK YOU, JULIE. 7160 05:17:16,361 --> 05:17:17,863 THAT WAS AN EXCELLENT TALK. 7161 05:17:17,863 --> 05:17:19,898 I'M EXCITED ABOUT THE GROWING 7162 05:17:19,898 --> 05:17:20,866 NUMBER OF SICKLE CELL CENTERS 7163 05:17:20,866 --> 05:17:24,269 ACROSS THE COUNTRY. 7164 05:17:24,269 --> 05:17:27,339 THANK YOU. 7165 05:17:27,339 --> 05:17:37,416 >> 7166 05:17:38,650 --> 05:17:39,117 >> OKAY. 7167 05:17:39,117 --> 05:17:40,552 LOOKS LIKE WE'RE A COUPLE 7168 05:17:40,552 --> 05:17:44,556 MINUTES AHEAD BUT THAT'S GREAT. 7169 05:17:44,556 --> 05:17:48,193 SO OUR NEXT TALK ACTUALLY WAS 7170 05:17:48,193 --> 05:17:49,895 SCHEDULED FOR 2:45 BUT WE'RE A 7171 05:17:49,895 --> 05:17:50,829 LITTLE EARLY. 7172 05:17:50,829 --> 05:17:52,197 THAT'S OKAY. 7173 05:17:52,197 --> 05:17:55,100 THE NEXT TALK WILL BE GENE 7174 05:17:55,100 --> 05:17:57,502 THERAPY FOR SICKLE CELL FROM 7175 05:17:57,502 --> 05:17:59,171 CLINICAL DEVELOPMENT TO 7176 05:17:59,171 --> 05:17:59,938 LONG-TERM FOLLOW-UP. 7177 05:17:59,938 --> 05:18:08,981 DR. ON ATH THTH THTH THTHEN -- N 7178 05:18:08,981 --> 05:18:13,051 AND DR. ALEXIS LEONARD. 7179 05:18:13,051 --> 05:18:16,488 >> I'LL MAKE THIS PRESENTATION 7180 05:18:16,488 --> 05:18:19,224 ON BEHALF OF THE ST. JUDE STAGES 7181 05:18:19,224 --> 05:18:20,826 TEAM AND DR. YEN. 7182 05:18:20,826 --> 05:18:21,793 WHAT I'LL TALK TO YOU ABOUT 7183 05:18:21,793 --> 05:18:25,030 TODAY IS THE UPCOMING CLINICAL 7184 05:18:25,030 --> 05:18:27,866 TRIAL THAT ST. JUDE HAS BEEN 7185 05:18:27,866 --> 05:18:29,468 WORKING ON FROM PRE CLINICAL 7186 05:18:29,468 --> 05:18:32,738 DEVELOPMENT TO OUR FOR LONG-TERM 7187 05:18:32,738 --> 05:18:33,005 FOLLOW-UP. 7188 05:18:33,005 --> 05:18:36,842 THIS IS KIND OF HOPEFULLY A NICE 7189 05:18:36,842 --> 05:18:39,544 COME TOGETHER OF THIS MORNING OF 7190 05:18:39,544 --> 05:18:42,214 THE BASIC SCIENCE TALKS AND THIS 7191 05:18:42,214 --> 05:18:46,485 GREAT CONVERSATION WE JUST HAD 7192 05:18:46,485 --> 05:18:47,786 ABOUT THE PLANS HOW TO INVOLVE 7193 05:18:47,786 --> 05:18:49,221 THE PATIENT IN THE PROCESS AND 7194 05:18:49,221 --> 05:18:50,622 THE MOVING FORWARD. 7195 05:18:50,622 --> 05:18:52,891 I'LL TELL YOU WHAT WE INTEND TO 7196 05:18:52,891 --> 05:19:03,168 DO AT ST. JUDE. 7197 05:19:03,802 --> 05:19:04,503 I WANT TO TALK ABOUT SICKLE CELL 7198 05:19:04,503 --> 05:19:14,846 DISEASE AT ST. JUDE. 7199 05:19:15,681 --> 05:19:16,181 AND WE SEE DISEASE THROUGH 7200 05:19:16,181 --> 05:19:24,122 TREATMENT. 7201 05:19:24,122 --> 05:19:28,493 SO ST. JUDE HAS A ROBUST HISTORY 7202 05:19:28,493 --> 05:19:30,128 OF SICKLE CELL DISEASE SINCE ITS 7203 05:19:30,128 --> 05:19:32,030 FOUNDING IN THE 1960s. 7204 05:19:32,030 --> 05:19:34,232 WE WERE ONE OF THE FIRST 7205 05:19:34,232 --> 05:19:35,267 COMPREHENSIVE RESEARCH CENTERS 7206 05:19:35,267 --> 05:19:37,602 ON BEHALF OF DR. DIGS AND 7207 05:19:37,602 --> 05:19:39,271 JACKSON AND WERE THE HOSPITAL 7208 05:19:39,271 --> 05:19:40,739 THAT TREATED THE FIRST PATIENT 7209 05:19:40,739 --> 05:19:41,740 CURED OF SICKLE CELL DISEASE 7210 05:19:41,740 --> 05:19:43,875 FROM A BONE MARROW TRANSPLANT IN 7211 05:19:43,875 --> 05:19:45,077 THE EARLY 1980s. 7212 05:19:45,077 --> 05:19:48,313 WE CURRENTLY TREAT ABOUT 900 7213 05:19:48,313 --> 05:19:49,981 PATIENTS WITH SICKLE CELL 7214 05:19:49,981 --> 05:19:51,783 DISEASE ACROSS FOUR STATES. 7215 05:19:51,783 --> 05:19:53,518 THE VAST MAJORITY OF OUR 7216 05:19:53,518 --> 05:19:56,254 PATIENTS PARTICIPATE IN RESEARCH 7217 05:19:56,254 --> 05:19:58,824 WHETHER THAT'S NEW DRUGS OR 7218 05:19:58,824 --> 05:20:01,593 DIAGNOSTIC TOOLS OR CURATIVE 7219 05:20:01,593 --> 05:20:06,598 THERAPIES WHICH WE'LL TALK ABOUT 7220 05:20:06,598 --> 05:20:08,500 TODAY AND IMPORTANTLY WE HAVE 7221 05:20:08,500 --> 05:20:09,968 THE SICKLE CELL RESEARCH AND 7222 05:20:09,968 --> 05:20:12,838 INTERVENTION PROGRAM STARTED BY 7223 05:20:12,838 --> 05:20:19,678 DR. HINKENS AND WE'RE STARTING 7224 05:20:19,678 --> 05:20:23,115 WITH HER LEADERSHIP TO BUILD A 7225 05:20:23,115 --> 05:20:24,282 GLOBAL PRESENCE IN SECOND 7226 05:20:24,282 --> 05:20:26,618 HALFED. 7227 05:20:26,618 --> 05:20:29,087 -- IN SICKLE CELL DISEASE. 7228 05:20:29,087 --> 05:20:31,022 I WANT TO TALK ABOUT OUR 7229 05:20:31,022 --> 05:20:33,825 UPCOMING STUDY AND PRECLINICAL 7230 05:20:33,825 --> 05:20:36,561 WORK FOR STUDY FOR SICKLE CELL 7231 05:20:36,561 --> 05:20:37,596 DISEASE THROUGH FETAL HEMOGLOBIN 7232 05:20:37,596 --> 05:20:37,863 INDUCTION. 7233 05:20:37,863 --> 05:20:44,469 THIS HAS ALL BEEN TALKED ABOUT 7234 05:20:44,469 --> 05:20:48,273 TODAY BUT THE IDEA IS TO MIMIC 7235 05:20:48,273 --> 05:20:56,515 THE VARIANTS IN WHAT CAUSES HPFH 7236 05:20:56,515 --> 05:20:57,816 AND TURNING FETAL HEMOGLOBIN IN 7237 05:20:57,816 --> 05:21:00,051 A PAIN CELLULAR DISTRIBUTION. 7238 05:21:00,051 --> 05:21:04,389 THIS STUDY IS TARGETING 7239 05:21:04,389 --> 05:21:10,595 SPECIFICALLY THE GAMMA GLOBIN 7240 05:21:10,595 --> 05:21:11,196 PROMOTER. 7241 05:21:11,196 --> 05:21:13,031 YOU HEARD ABOUT THIS THIS 7242 05:21:13,031 --> 05:21:17,836 MORNING FROM DR. BAUER AND USING 7243 05:21:17,836 --> 05:21:20,972 CAS 9 AND THE ERYTHROID ENHANCER 7244 05:21:20,972 --> 05:21:22,674 WITH THE TARGET BEING DISRUPTION 7245 05:21:22,674 --> 05:21:33,185 OF THE ENHANCER WITH THE CELL 7246 05:21:34,653 --> 05:21:37,722 AND WE'RE TALK BEING ABOUT USING 7247 05:21:37,722 --> 05:21:39,157 CAS 9 OR ANOTHER ONGOING TRIAL 7248 05:21:39,157 --> 05:21:42,294 TO CREATE INDELS AT THE GAMMA 7249 05:21:42,294 --> 05:21:50,735 GLOBIN PROMOTER. 7250 05:21:50,735 --> 05:21:54,739 IT BLOCKED THE BCL11A AND THE 7251 05:21:54,739 --> 05:21:56,508 TRIAL WE'RE TALKING ABOUT 7252 05:21:56,508 --> 05:22:04,516 REFERRED TO AS SAGES THE 7253 05:22:04,516 --> 05:22:07,352 ST. JUDE TARGETED SICKLE CELL 7254 05:22:07,352 --> 05:22:16,394 DISEASE FUNDED BY THE UL1 GRANT. 7255 05:22:16,394 --> 05:22:18,296 THE PROCESS OF CLINICAL TRIAL 7256 05:22:18,296 --> 05:22:20,265 TRIAL WAS TO GET THE IND 7257 05:22:20,265 --> 05:22:21,867 APPROVAL THE PAST SPRING. 7258 05:22:21,867 --> 05:22:23,735 I WANT TO SHOW SOME PRE 7259 05:22:23,735 --> 05:22:28,473 CLINICALS FROM THE CMC DATA TO 7260 05:22:28,473 --> 05:22:31,543 OPTIMIZE AND SCALE UP. 7261 05:22:31,543 --> 05:22:39,684 SO FIRST GENOME EDITING AT THE 7262 05:22:39,684 --> 05:22:44,422 MINUS 115 SITE TO INDUCE 7263 05:22:44,422 --> 05:22:46,691 HEMOGLOBIN AND AFTER 7264 05:22:46,691 --> 05:22:47,325 TRANSPLANTING TO THE HEALTHY 7265 05:22:47,325 --> 05:22:52,797 CELLS IN MICE WE COULD SHOW AND 7266 05:22:52,797 --> 05:22:54,966 COMPARE TO OTHER HEMOGLOBIN 7267 05:22:54,966 --> 05:22:59,838 STRATEGIES LIKE THE ENHANCER OR 7268 05:22:59,838 --> 05:23:01,273 TARGETING MOTIF THAT ACROSS THE 7269 05:23:01,273 --> 05:23:02,874 BOARD IN THE INPUT AND 17 WEEKS 7270 05:23:02,874 --> 05:23:04,342 LATER IN MICE YOU GET HIGH 7271 05:23:04,342 --> 05:23:12,284 EDITING RATIOS. 7272 05:23:12,284 --> 05:23:13,852 THE FETAL HEMOGLOBIN INDUCTION 7273 05:23:13,852 --> 05:23:17,656 WAS HIGHEST USING THE SITE IN 7274 05:23:17,656 --> 05:23:19,124 COMPARISON TO THE OTHER BINDING 7275 05:23:19,124 --> 05:23:29,467 MOTIFS OR ENHANCERS. 7276 05:23:49,054 --> 05:23:50,288 YOU HAVE SIGNIFICANT REDUCTION 7277 05:23:50,288 --> 05:23:56,494 IN SICKLING. 7278 05:23:56,494 --> 05:23:58,496 AS WE TRANSFERRED THIS TO SCALE 7279 05:23:58,496 --> 05:24:01,066 UP AND OPTIMIZE THERE'S 7280 05:24:01,066 --> 05:24:02,400 VARIABLES THAT GO INTO THIS YOU 7281 05:24:02,400 --> 05:24:04,502 CAN SEE LISTED HERE AND 7282 05:24:04,502 --> 05:24:07,272 ULTIMATELY A DESIGN OF 7283 05:24:07,272 --> 05:24:10,442 EXPERIMENT STUDIES WE CAN 7284 05:24:10,442 --> 05:24:12,143 EXAMINE MULTIPLE PARAMETERS 7285 05:24:12,143 --> 05:24:14,612 SIMULTANEOUSLY AND WE FOUND THE 7286 05:24:14,612 --> 05:24:19,851 CAS 9 CONCENTRATION AND CELL 7287 05:24:19,851 --> 05:24:30,295 CONCENTRATION AND WE USED 7288 05:24:43,341 --> 05:24:53,718 HEALTHY DONORS HECs WITH 7289 05:24:54,619 --> 05:24:57,188 ELECTROPORATED WITH OUR CAS 9 7290 05:24:57,188 --> 05:25:00,291 SHOWING INDUCTION IN VIVO ACROSS 7291 05:25:00,291 --> 05:25:10,435 DONORS. 7292 05:25:14,572 --> 05:25:17,475 AND AS A MEMBER OF ST. JUDE WE 7293 05:25:17,475 --> 05:25:21,713 FOUND NO DETECTABLE OFF TARGET 7294 05:25:21,713 --> 05:25:22,947 MUTATIONS FROM AFRICAN AMERICAN 7295 05:25:22,947 --> 05:25:29,521 DONORS AND WHEN WE TRANSPLANTED 7296 05:25:29,521 --> 05:25:31,489 WE HAD NO ADVERSE OUTCOMES IN 7297 05:25:31,489 --> 05:25:32,957 OUR MICE. 7298 05:25:32,957 --> 05:25:35,894 AND NOW I WANT TO TRANSFER TO 7299 05:25:35,894 --> 05:25:38,530 THE WORK WE FELT WE WERE ABLE TO 7300 05:25:38,530 --> 05:25:42,300 MOVE FORWARD FROM THE CLINICAL 7301 05:25:42,300 --> 05:25:44,469 TO HEMATOLOGY TO PATIENTS. 7302 05:25:44,469 --> 05:25:52,710 THIS STUDY REFERRED TO IS A CAS 7303 05:25:52,710 --> 05:25:53,912 9 TRIAL AT THE HEMOGLOBIN 7304 05:25:53,912 --> 05:25:56,114 PROMOTER AND THE PRODUCT IS 7305 05:25:56,114 --> 05:25:58,249 BEING MANUFACTURED ON SITE AT 7306 05:25:58,249 --> 05:26:00,652 THE ST. JUDE CHILDREN'S AMP AND 7307 05:26:00,652 --> 05:26:03,388 WILL START THE STUDY ONCE A FEW 7308 05:26:03,388 --> 05:26:04,322 PATIENTS HAVE BEEN TREATED WILL 7309 05:26:04,322 --> 05:26:05,190 BE ABLE TO EXPAND TO MULTIPLE 7310 05:26:05,190 --> 05:26:14,099 CENTERS. 7311 05:26:14,099 --> 05:26:15,867 IN BRIEF THE EXCLUSIONARY 7312 05:26:15,867 --> 05:26:17,268 CRITERIA ARE SIMILAR TO THE 7313 05:26:17,268 --> 05:26:19,404 CLINICAL TRIALS CURRENTLY BEING 7314 05:26:19,404 --> 05:26:19,571 RUN. 7315 05:26:19,571 --> 05:26:23,508 BRIEFLY THESE ARE STARTING WITH 7316 05:26:23,508 --> 05:26:24,042 ADULT PATIENTS. 7317 05:26:24,042 --> 05:26:27,112 WE ARE EXCLUDING SC PATIENTS AT 7318 05:26:27,112 --> 05:26:28,346 THIS TIME AND EXCLUDEING 7319 05:26:28,346 --> 05:26:32,283 PATIENTS WITH CURRENT VOEs OR ON 7320 05:26:32,283 --> 05:26:33,985 CHRONIC TRAN FUSIONS EXCEPT FOR 7321 05:26:33,985 --> 05:26:35,854 PRIMARY OR SECONDARY STROKE 7322 05:26:35,854 --> 05:26:37,021 PREVENTION AND THOSE WITH A 7323 05:26:37,021 --> 05:26:40,525 MATCHED SIBLING OR HISTORY OF 7324 05:26:40,525 --> 05:26:42,127 STROKE. 7325 05:26:42,127 --> 05:26:43,828 THIS LOOKS FUNNY BUT WHAT I WANT 7326 05:26:43,828 --> 05:26:49,601 TO DESCRIBE TO YOU IS PART OF 7327 05:26:49,601 --> 05:26:52,504 SUPPLEMENTING THE DISCUSSION 7328 05:26:52,504 --> 05:26:58,376 WITH DR. KANTER AND WE DEVELOPED 7329 05:26:58,376 --> 05:27:01,779 THE ST. JUDE HEMATOLOGY GENE AND 7330 05:27:01,779 --> 05:27:04,382 CHROME THERAPY PROGRAM RUN BY 7331 05:27:04,382 --> 05:27:06,217 MYSELF AND MY COLLEAGUE 7332 05:27:06,217 --> 05:27:06,684 DR. SHARMA. 7333 05:27:06,684 --> 05:27:09,888 AT THE BOTTOM IN THE SMALL FONT 7334 05:27:09,888 --> 05:27:13,024 YOU CAN SEE ALL THE MANY 7335 05:27:13,024 --> 05:27:14,159 MULTI-DISCIPLINARY TEAM MEMBERS. 7336 05:27:14,159 --> 05:27:14,759 ULTIMATELY THE PATIENT WAS AT 7337 05:27:14,759 --> 05:27:16,594 THE CENTER. 7338 05:27:16,594 --> 05:27:18,363 IT'S CENTERED AROUND SHARED 7339 05:27:18,363 --> 05:27:23,134 DECISION MAKING. 7340 05:27:23,134 --> 05:27:25,069 OF COURSE PATIENTS COME IN AND 7341 05:27:25,069 --> 05:27:28,506 THE CONSULTATION HAS BEEN 7342 05:27:28,506 --> 05:27:31,643 MENTIONED WE'LL TALK ABOUT THIS 7343 05:27:31,643 --> 05:27:35,580 CLINICAL TRIAL AND THE FDA 7344 05:27:35,580 --> 05:27:37,849 APPROVED OPTIONS AND ALLO GENEIC 7345 05:27:37,849 --> 05:27:39,551 TRANSPLANT OR NOT DOING THESE 7346 05:27:39,551 --> 05:27:40,919 AND THE RIGHT TIME. 7347 05:27:40,919 --> 05:27:43,188 AND AS PATIENTS MOVE ALONG THE 7348 05:27:43,188 --> 05:27:46,958 PROCESS WE INTEND TO FOLLOW FOR 7349 05:27:46,958 --> 05:27:51,362 15 YEARS IN OUR COMBINED 7350 05:27:51,362 --> 05:27:53,565 TRANSFORMATIVE CELL THERAPY 7351 05:27:53,565 --> 05:27:55,567 CROSSING THE GENE THERAPY 7352 05:27:55,567 --> 05:27:55,800 CLINIC. 7353 05:27:55,800 --> 05:28:00,371 ONE IMPORTANT DISTINCTION I WANT 7354 05:28:00,371 --> 05:28:02,574 TO MAKE SINCE IT'S A PRODUCT 7355 05:28:02,574 --> 05:28:03,408 WE'RE ABLE TO MANUFACTURE 7356 05:28:03,408 --> 05:28:05,310 OURSELVES IN CONTRAST TO THE 7357 05:28:05,310 --> 05:28:07,378 CLINICAL TRIALS WHERE THE WAIT 7358 05:28:07,378 --> 05:28:08,980 TIME BETWEEN DRUG PRODUCT 7359 05:28:08,980 --> 05:28:10,715 MANUFACTURER AND TRANSPLANT CAN 7360 05:28:10,715 --> 05:28:15,720 BE UPWARDS OF SIX MONTHS WE 7361 05:28:15,720 --> 05:28:18,389 ANTICIPATE ONE OR TWO MONTHS 7362 05:28:18,389 --> 05:28:18,957 FROM DRUG MANUFACTURE GOING 7363 05:28:18,957 --> 05:28:22,060 TOWARDS TRANSPLANT. 7364 05:28:22,060 --> 05:28:23,294 THE BIGGEST QUESTION IN THE ROOM 7365 05:28:23,294 --> 05:28:26,464 AND FOR ALL OF US IS HOW TO 7366 05:28:26,464 --> 05:28:28,499 FOLLOW THESE PATIENTS LONG-TERM 7367 05:28:28,499 --> 05:28:32,503 AND HOW CAN WE AT ST. JUDE DO 7368 05:28:32,503 --> 05:28:33,738 THIS AND HARMONIZE WITH 7369 05:28:33,738 --> 05:28:38,109 EVERYBODY ELSE WANTING TO DO 7370 05:28:38,109 --> 05:28:40,912 THIS BECAUSE GENE THERAPY IS 7371 05:28:40,912 --> 05:28:42,914 TRANSFORMATIVE UNTIL ALL THE 7372 05:28:42,914 --> 05:28:43,815 OUTCOMES ARE BETTER UNDERSTOOD. 7373 05:28:43,815 --> 05:28:47,085 WHAT WE INTEND TO DO AT ST. JUDE 7374 05:28:47,085 --> 05:28:49,420 AND I THINK THE WHOLE AUDIENCE 7375 05:28:49,420 --> 05:28:51,522 WOULD AGREE WE NEED TO KNOW MORE 7376 05:28:51,522 --> 05:28:52,890 THAN WHAT HAPPENS TO PAIN. 7377 05:28:52,890 --> 05:28:54,959 WE NEED TO KNOW IS THERE ONE 7378 05:28:54,959 --> 05:28:56,227 PRODUCT BETTER THAN THE OTHER. 7379 05:28:56,227 --> 05:28:59,597 WE NEED TO KNOW AS WE START TO 7380 05:28:59,597 --> 05:29:04,836 MAKE ALL THE PROCESS 7381 05:29:04,836 --> 05:29:09,140 IMPROVEMENTS GET RID OF DIFULSAN 7382 05:29:09,140 --> 05:29:11,809 AND WE INTEND TO DO THIS THROUGH 7383 05:29:11,809 --> 05:29:16,014 OUR SCCRIP COHORT STARTED IN 7384 05:29:16,014 --> 05:29:16,414 2014. 7385 05:29:16,414 --> 05:29:20,818 THIS IS OUR LONGITUDINAL AND BIO 7386 05:29:20,818 --> 05:29:25,023 REPOSITORY COHORT OF ALL OF OUR 7387 05:29:25,023 --> 05:29:25,590 PATIENTS WITH SECRETARY OF 7388 05:29:25,590 --> 05:29:28,493 DEFENSE FROM PEDIATRICS THROUGH 7389 05:29:28,493 --> 05:29:30,361 THE ADULT POPULATION AS THEY'RE 7390 05:29:30,361 --> 05:29:31,963 TRANSITIONED OUT OF ST. JUDE. 7391 05:29:31,963 --> 05:29:34,465 WE HAVE JUST OVER 1500 PATIENTS 7392 05:29:34,465 --> 05:29:36,701 ENROLLED AND IMPORTANTLY WE HAVE 7393 05:29:36,701 --> 05:29:38,770 SEPARATED IT OUT INTO MULTIPLE 7394 05:29:38,770 --> 05:29:42,874 WORKING GROUPS THAT HAVE 7395 05:29:42,874 --> 05:29:43,641 ORGAN-SPECIFIC EXPERTS FROM 7396 05:29:43,641 --> 05:29:45,476 ACROSS THE COUNTRY. 7397 05:29:45,476 --> 05:29:47,679 WE HAVE ABOUT 70 PEOPLE 7398 05:29:47,679 --> 05:29:48,880 INTERESTED AND PART OF THE 7399 05:29:48,880 --> 05:29:50,882 WORKING GROUPS. 7400 05:29:50,882 --> 05:29:56,988 IT HAS A PLACE FOR ROBUST 7401 05:29:56,988 --> 05:30:00,925 ABILITY TO GENERATE AND ANALYZE 7402 05:30:00,925 --> 05:30:03,294 THE DATA. 7403 05:30:03,294 --> 05:30:05,163 WE'RE INVOLVED IN THE TOP MED 7404 05:30:05,163 --> 05:30:06,331 CONSORTIUM WITH ST. JUDE AND 7405 05:30:06,331 --> 05:30:08,333 VANDERBILT AND THE UNIVERSITY OF 7406 05:30:08,333 --> 05:30:13,971 ILLINOIS TO LOOK AT THE THINGS 7407 05:30:13,971 --> 05:30:15,973 DR. FITZHUGH DISCUSSED IN GERM 7408 05:30:15,973 --> 05:30:17,175 LIN AND HEMATOPOIESIS. 7409 05:30:17,175 --> 05:30:19,844 OUR INTENT IS ALL PATIENTS WHO 7410 05:30:19,844 --> 05:30:22,814 RECEIVE A TRANSFORMATIVE THERAPY 7411 05:30:22,814 --> 05:30:24,682 WILL WILL BE FOLLOWED WITHIN THE 7412 05:30:24,682 --> 05:30:26,050 INFRASTRUCTURE WHICH ALREADY 7413 05:30:26,050 --> 05:30:28,519 INCLUDES THE PATIENTS RECEIVING 7414 05:30:28,519 --> 05:30:29,387 STANDARD OF CARE. 7415 05:30:29,387 --> 05:30:32,490 AND SO WITH THIS WE ARE OPEN TO 7416 05:30:32,490 --> 05:30:34,359 THE COLLABORATIONS THAT CAN 7417 05:30:34,359 --> 05:30:36,661 OCCUR AND CERTAINLY DEVELOPING A 7418 05:30:36,661 --> 05:30:39,931 STANDARDIZED PARAMETER TO 7419 05:30:39,931 --> 05:30:43,234 MEASURE THE OUTCOMES AFTER ALL 7420 05:30:43,234 --> 05:30:45,269 TYPES OF TRANSPLANT AND NOT 7421 05:30:45,269 --> 05:30:46,304 HAVING A TRANSPLANT FOR PATIENTS 7422 05:30:46,304 --> 05:30:52,377 WITH SICKLE CELL DISEASE. 7423 05:30:52,377 --> 05:30:55,413 THIS IS TO SHOW IS TAKES A LARGE 7424 05:30:55,413 --> 05:30:59,350 TEAM TO THE SUB SPECIALISTS AND 7425 05:30:59,350 --> 05:31:05,623 THE ENTIRE CLINICAL TRIALS TEAM 7426 05:31:05,623 --> 05:31:07,925 AND HEMATOLOGISTS WHO GOT THIS 7427 05:31:07,925 --> 05:31:09,026 OFF THE GROUND. 7428 05:31:09,026 --> 05:31:12,263 FROM HERE, WE WANT TO 7429 05:31:12,263 --> 05:31:14,632 ACKNOWLEDGE ALL THE IMPORTANT 7430 05:31:14,632 --> 05:31:15,400 PARTIES. 7431 05:31:15,400 --> 05:31:18,836 OUR COLLABORATORS AND NHLBI 7432 05:31:18,836 --> 05:31:22,206 FUNDING AND THEN AT THE TOP IS 7433 05:31:22,206 --> 05:31:24,375 MY E-MAIL IF YOU HAVE A PATIENT 7434 05:31:24,375 --> 05:31:25,610 YOU'D LIKE TO REFER. 7435 05:31:25,610 --> 05:31:27,845 THIS TRIAL SHOULD BE ACTIVE AND 7436 05:31:27,845 --> 05:31:29,447 OPEN WITHIN THE NEXT FEW MONTHS 7437 05:31:29,447 --> 05:31:30,615 AND WITH THAT I'M HAPPY TO TAKE 7438 05:31:30,615 --> 05:31:40,858 ANY QUESTIONS. 7439 05:31:46,097 --> 05:31:49,066 >> WE HAVE ONE COMMENT ON LINE. 7440 05:31:49,066 --> 05:31:51,169 FOR ME THE CRITICAL QUESTION IS 7441 05:31:51,169 --> 05:31:52,503 WHETHER ONE TREATMENT IS SAFER 7442 05:31:52,503 --> 05:31:55,673 THAN ANOTHER WHICH HINGES ON 7443 05:31:55,673 --> 05:31:59,210 HAVING A UNIFORM COMPLETE 7444 05:31:59,210 --> 05:32:01,612 LONG-TERM FOLLOW-UP PROCESS 7445 05:32:01,612 --> 05:32:04,215 GATHER THE CRITICAL SAFETY DATA 7446 05:32:04,215 --> 05:32:05,550 WHICH VARIES FROM STUDY TO 7447 05:32:05,550 --> 05:32:07,018 STUDIO AND SPONSOR TO SPONSOR. 7448 05:32:07,018 --> 05:32:09,787 >> YES, I AGREE. 7449 05:32:09,787 --> 05:32:17,662 AND DR. KANTER AGREES AS WELL. 7450 05:32:17,662 --> 05:32:19,597 TO THE REASON WE'RE HERE IS TO 7451 05:32:19,597 --> 05:32:23,801 AGREE ON THE PACT WE NEED 7452 05:32:23,801 --> 05:32:24,135 HARMONIZATION. 7453 05:32:24,135 --> 05:32:27,538 WE CAN START AS SIMPLE AS MAKING 7454 05:32:27,538 --> 05:32:30,842 SURE YOUR STUDY THAT THESE NHLBI 7455 05:32:30,842 --> 05:32:35,246 STUDIES ARE ALL HARMONIZED AND 7456 05:32:35,246 --> 05:32:38,583 THEN WORKING WITH MAKING SURE 7457 05:32:38,583 --> 05:32:40,251 EVERYBODY THAT'S GOING IN IS 7458 05:32:40,251 --> 05:32:45,623 WHAT WE'RE FOLLOWING AND ALL OF 7459 05:32:45,623 --> 05:32:49,427 THESE DISPARATE REGISTRIES. 7460 05:32:49,427 --> 05:32:51,963 THE ONLY WAY WE'LL KNOW IS IF WE 7461 05:32:51,963 --> 05:32:54,665 HARMONIZE THIS MORE BROADLY AND 7462 05:32:54,665 --> 05:32:57,235 SO I THINK MEETINGS LIKE THIS IS 7463 05:32:57,235 --> 05:32:59,136 A CALL TO ACTION THAT THAT'S 7464 05:32:59,136 --> 05:33:07,712 WHAT NEEDS TO HAPPEN. 7465 05:33:07,712 --> 05:33:08,179 >> OKAY. 7466 05:33:08,179 --> 05:33:09,547 ANYMORE QUESTIONS FROM THE 7467 05:33:09,547 --> 05:33:10,548 PANEL? 7468 05:33:10,548 --> 05:33:12,717 THANK YOU VERY MUCH, ALEXIS FOR 7469 05:33:12,717 --> 05:33:16,487 A GREAT TALK. 7470 05:33:16,487 --> 05:33:19,690 NOW WE HAVE A WONDERFUL SESSION 7471 05:33:19,690 --> 05:33:26,531 THE UPDATES FROM NHLBI CURE 7472 05:33:26,531 --> 05:33:27,164 SICKLE CELL DISEASE INITIATIVE 7473 05:33:27,164 --> 05:33:37,608 CHAIRED BY HEATHER AVANT. 7474 05:33:45,349 --> 05:33:47,118 >> I'M GOING INTRODUCE A COUPLE 7475 05:33:47,118 --> 05:33:50,321 PEOPLE WHO WILL COME UP. 7476 05:33:50,321 --> 05:33:54,592 DR. JOHN MANIS WHO WILL TALK 7477 05:33:54,592 --> 05:33:57,094 ABOUT OPTIMIZING PRE-TRANSPLANT 7478 05:33:57,094 --> 05:33:58,296 ACCESS TO GENE THERAPY FOR 7479 05:33:58,296 --> 05:34:04,201 SICKLE CELL DISEASE AND PART OF 7480 05:34:04,201 --> 05:34:06,938 THE WORKING GROUP TO CURE SICKLE 7481 05:34:06,938 --> 05:34:17,481 CELL AND DR. CECELIA VALRIE AND 7482 05:34:21,018 --> 05:34:23,454 JERLYM PORTER TALKING ABOUT 7483 05:34:23,454 --> 05:34:25,456 PSYCHOSOCIAL READINESS AND 7484 05:34:25,456 --> 05:34:28,059 SUPPORT FOR PRE AND POST-GENE 7485 05:34:28,059 --> 05:34:28,993 THERAPY IN SICKLE CELL DISEASE. 7486 05:34:28,993 --> 05:34:36,400 I'LL BE CO-HOSTING AFTER THAT 7487 05:34:36,400 --> 05:34:46,777 WITH ADRIENNE SHAPIRO. 7488 05:34:50,715 --> 05:34:56,787 >> IT'S GREAT TO GO OVER THE 7489 05:34:56,787 --> 05:34:58,356 TOPIC. 7490 05:34:58,356 --> 05:35:00,725 IT'S BEEN GREAT TO BRING THE 7491 05:35:00,725 --> 05:35:06,430 PRESENTATION TODAY AND TO BE 7492 05:35:06,430 --> 05:35:14,038 ABLE 7493 05:35:14,038 --> 05:35:18,342 ABLE TO DISCUSS THE WORKING 7494 05:35:18,342 --> 05:35:19,877 GROUP AND WHAT WE'VE DONE AND 7495 05:35:19,877 --> 05:35:20,611 WHAT WE'RE THINKING ABOUT AND 7496 05:35:20,611 --> 05:35:30,187 WHERE WE'RE GOING. 7497 05:35:30,187 --> 05:35:32,123 JUST ONE DISCLOSURE THAT'S MINE. 7498 05:35:32,123 --> 05:35:36,427 THE WORKING GROUP IS COMPROMISED 7499 05:35:36,427 --> 05:35:39,664 OF INDIVIDUALS AND TRIED TO MAKE 7500 05:35:39,664 --> 05:35:41,399 IT INCLUSIVE ACADEMIC, INDUSTRY, 7501 05:35:41,399 --> 05:35:43,834 GOVERNMENT ORGANIZERS. 7502 05:35:43,834 --> 05:35:45,202 EVERYBODY COMING TOGETHER TO 7503 05:35:45,202 --> 05:35:48,406 UNDERSTAND THE CHALLENGES 7504 05:35:48,406 --> 05:35:52,476 ASSOCIATED WITH MOBILIZATION AND 7505 05:35:52,476 --> 05:36:03,020 AFER -- APHERESIS CORRUPTION AND 7506 05:36:09,460 --> 05:36:11,328 THERE WAS CONSIDERING IN HOW 7507 05:36:11,328 --> 05:36:14,465 WE'D GET SIZE BUT THE DEEP 7508 05:36:14,465 --> 05:36:16,267 QUESTIONS SURROUNDING 7509 05:36:16,267 --> 05:36:18,335 MOBILIZATION, SURROUNDING 7510 05:36:18,335 --> 05:36:19,203 TECHNICALLY HOW DO WE COLLECT 7511 05:36:19,203 --> 05:36:22,039 WASN'T KNOWN. 7512 05:36:22,039 --> 05:36:25,176 THAT WAS ONLY FIVE TO 10 YEARS 7513 05:36:25,176 --> 05:36:26,077 AGO. 7514 05:36:26,077 --> 05:36:28,479 IT'S NOT JUST THE PROBLEM WE'VE 7515 05:36:28,479 --> 05:36:30,548 BEEN THINKING ABOUT THE 20 OR 7516 05:36:30,548 --> 05:36:30,981 30. 7517 05:36:30,981 --> 05:36:36,220 IT'S SO ESTABLISH THE BEST 7518 05:36:36,220 --> 05:36:36,754 PRACTICE GUIDELINES AND 7519 05:36:36,754 --> 05:36:44,495 UNDERSTAND THE KNOWLEDGE GAPS. 7520 05:36:44,495 --> 05:36:48,899 AFTER FIRST WOE WE WANTED TO 7521 05:36:48,899 --> 05:36:52,203 UNDERSTAND THE LANDSCAPE AND 7522 05:36:52,203 --> 05:36:53,604 DEVELOPED A SURVEY WE 7523 05:36:53,604 --> 05:36:54,438 DISTRIBUTED TO COLLECTION 7524 05:36:54,438 --> 05:36:58,175 CENTERS TO TRY TO UNDERSTAND 7525 05:36:58,175 --> 05:37:02,346 WHAT IS EVERYBODY DOING FOR 7526 05:37:02,346 --> 05:37:03,147 COLLECTIONS FOR SICKLE CELL GENE 7527 05:37:03,147 --> 05:37:05,049 THERAPY AND ALSO WHAT THEY'RE 7528 05:37:05,049 --> 05:37:07,985 DOING DIFFERENT CENTERS FOR 7529 05:37:07,985 --> 05:37:08,786 PATIENTS WITH DEVELOPED. 7530 05:37:08,786 --> 05:37:11,555 I WANT TO TAKE ONE STEP BECOME 7531 05:37:11,555 --> 05:37:13,858 AT THIS POINT TO HELP YOU 7532 05:37:13,858 --> 05:37:16,694 UNDERSTAND WHEN WE'RE TALKING 7533 05:37:16,694 --> 05:37:18,429 ABOUT STEM CELL COLLECTIONS FOR 7534 05:37:18,429 --> 05:37:21,398 SICKLE CELL DISEASE WE'RE ALSO 7535 05:37:21,398 --> 05:37:26,604 TALKING ABOUT OTHER REGIMENTS 7536 05:37:26,604 --> 05:37:31,842 I'LL GET INTO BUT HOW CAN 7537 05:37:31,842 --> 05:37:33,811 APHERESIS TRANSFUSION AND THOSE 7538 05:37:33,811 --> 05:37:38,883 THAT COLLECT STEM CELLS IMPROVE 7539 05:37:38,883 --> 05:37:41,719 THE HEALTH OF SICKLE CELL 7540 05:37:41,719 --> 05:37:44,021 PATIENTS. 7541 05:37:44,021 --> 05:37:49,193 THERE'S A WIDE VARIANT IN 7542 05:37:49,193 --> 05:37:52,897 COLLECTS AND MOST CENTERS SOME 7543 05:37:52,897 --> 05:37:58,636 OF SOME HAD ZERO COLLECTIONS FOR 7544 05:37:58,636 --> 05:37:58,903 DEVELOPED. 7545 05:37:58,903 --> 05:38:01,405 IT MEANT MANY COLLECTIONS. 7546 05:38:01,405 --> 05:38:06,110 THERE WAS ALSO WIDE VARIATION IN 7547 05:38:06,110 --> 05:38:06,977 STEM CELL COLLECTION PRACTICE 7548 05:38:06,977 --> 05:38:12,449 STANDARDS AROUND EXACTLY HOW 7549 05:38:12,449 --> 05:38:14,185 APHERESIS WAS PERFORMED 37 -- 7550 05:38:14,185 --> 05:38:15,252 PERFORMED. 7551 05:38:15,252 --> 05:38:17,121 THE PARAMETERS WERE NOTE 7552 05:38:17,121 --> 05:38:17,388 SPECIFIED. 7553 05:38:17,388 --> 05:38:21,325 THOSE WERE LEFT IN SOME SORT OF 7554 05:38:21,325 --> 05:38:23,427 RAY BECAUSE HEMATOLOGISTS WERE 7555 05:38:23,427 --> 05:38:25,963 THINKING ABOUT THIS IN THE WAY 7556 05:38:25,963 --> 05:38:29,033 OF WHY ARE WE DOING THE 7557 05:38:29,033 --> 05:38:29,300 EXCHANGE? 7558 05:38:29,300 --> 05:38:36,207 THIS IS AN EVOLVING FIELD. 7559 05:38:36,207 --> 05:38:37,575 WHAT ARE WE GOING TO SECOND HALF 7560 05:38:37,575 --> 05:38:39,076 PATIENTS TO IMPROVE THEIR HEALTH 7561 05:38:39,076 --> 05:38:39,977 FOR MOBILIZATION. 7562 05:38:39,977 --> 05:38:41,245 THAT IS A QUESTION NOT BROUGHT 7563 05:38:41,245 --> 05:38:42,179 UP BEFORE. 7564 05:38:42,179 --> 05:38:45,516 THE LAST PART IS VERY IMPORTANT 7565 05:38:45,516 --> 05:38:50,487 IS THERE'S A LACK OF DATA 7566 05:38:50,487 --> 05:38:50,788 COLLECTIONS. 7567 05:38:50,788 --> 05:38:54,425 HOW CAN WE SHARE THE INFORMATION 7568 05:38:54,425 --> 05:38:59,396 AMONGST COLLECTION CENTERS. 7569 05:38:59,396 --> 05:39:02,900 THE CHALLENGES OF THE PATIENTS 7570 05:39:02,900 --> 05:39:06,670 AND GENE THERAPY ONE IS ACCESS 7571 05:39:06,670 --> 05:39:09,173 TO THE RED CELL TRANSFUSION 7572 05:39:09,173 --> 05:39:11,976 REGIMENTS. 7573 05:39:11,976 --> 05:39:14,144 IN OTHER WORDS, WHO COULD GET 7574 05:39:14,144 --> 05:39:14,678 RED CELL EXCHANGE. 7575 05:39:14,678 --> 05:39:18,949 HOW PATIENTS ACCESS THIS? 7576 05:39:18,949 --> 05:39:22,953 ARE THEY IN SPECIALTY CENTERS 7577 05:39:22,953 --> 05:39:24,455 THAT UNDERSTAND WHEN TO GO TO 7578 05:39:24,455 --> 05:39:26,423 RED CELL EXCHANGE OR NOT TO OR 7579 05:39:26,423 --> 05:39:31,061 WHEN TO PULL THE TRIGGER AND 7580 05:39:31,061 --> 05:39:32,763 HAVE. 7581 05:39:32,763 --> 05:39:38,702 MOBILIZATION ACRONYMS ARE 7582 05:39:38,702 --> 05:39:44,008 CHALLENGING AND MANUFACTURING 7583 05:39:44,008 --> 05:39:53,817 MENG ODDS AND TO THE PRODUCT AND 7584 05:39:53,817 --> 05:40:01,458 IT'S SCALABLE. 7585 05:40:01,458 --> 05:40:04,495 SO TO THE PRESENT DAY CHALLENGES 7586 05:40:04,495 --> 05:40:06,730 ACCESS TO CENTERS OF EXCELLENCE. 7587 05:40:06,730 --> 05:40:10,000 THE EXTENDED WAIT PERIOD FOR 7588 05:40:10,000 --> 05:40:10,234 ACCESS. 7589 05:40:10,234 --> 05:40:12,136 IF YOU ASK FOR GENE THERAPY NOW 7590 05:40:12,136 --> 05:40:13,470 YOU'LL PROBABLY HAVE TO WAIT 7591 05:40:13,470 --> 05:40:14,171 CLOSE TO A YEAR. 7592 05:40:14,171 --> 05:40:18,909 AND HOW DO WE CHANGE THAT? 7593 05:40:18,909 --> 05:40:24,214 THAT'S SOMETHING DR. BAUER UP 7594 05:40:24,214 --> 05:40:30,087 EARLIER. 7595 05:40:30,087 --> 05:40:31,822 IF IT TAKES NINE MONTHS TO 7596 05:40:31,822 --> 05:40:33,123 PREPARE SOMEBODY FOR GENE 7597 05:40:33,123 --> 05:40:34,925 THERAPY, WHO IS TAKING CARE OF 7598 05:40:34,925 --> 05:40:35,926 THE PATIENT AND SCALE UP FOR 7599 05:40:35,926 --> 05:40:46,170 MANUFACTURING. 7600 05:40:55,479 --> 05:40:57,381 AND WE WILL REQUIRE A LARK 7601 05:40:57,381 --> 05:41:02,553 NUMBER OF CELLS AND PROBABLY YOU 7602 05:41:02,553 --> 05:41:10,227 WANT A LARGER DOSE. 7603 05:41:10,227 --> 05:41:12,396 THIS IS DIFFERENT FROM THE PAST 7604 05:41:12,396 --> 05:41:14,598 AND THIS DISTINCTION NEEDS STUDY 7605 05:41:14,598 --> 05:41:16,200 AND SPECIAL ATTENTION. 7606 05:41:16,200 --> 05:41:18,469 THERE'S INTRINSIC LOSS IN 7607 05:41:18,469 --> 05:41:18,802 MANUFACTURING. 7608 05:41:18,802 --> 05:41:21,205 DR. WILLIAMS BROUGHT UP THE 7609 05:41:21,205 --> 05:41:22,573 DIFFERENCES AMONGST THE TRIALS 7610 05:41:22,573 --> 05:41:26,777 AND HOW TO MANIPULATE THE CELLS 7611 05:41:26,777 --> 05:41:28,779 IF YOU'RE EXPANDING IN VITRO AND 7612 05:41:28,779 --> 05:41:31,849 HOW MANY DAYS IT TAKES TO 7613 05:41:31,849 --> 05:41:34,084 COLLECT AND HOW CELL COLLECTIONS 7614 05:41:34,084 --> 05:41:34,651 ARE PUT TOGETHER ALL THIS 7615 05:41:34,651 --> 05:41:43,627 MATTERS. 7616 05:41:43,627 --> 05:41:46,397 AND REAL LIFE LIMITATIONS TO THE 7617 05:41:46,397 --> 05:41:48,465 GENE THERAPY AND THERE WAS A 7618 05:41:48,465 --> 05:41:57,474 SIMILAR SLIDE. 7619 05:41:57,474 --> 05:41:59,943 AND THIS ISN'T TO POINT OUT 7620 05:41:59,943 --> 05:42:02,446 FAILURE OF THE GROUP BUT TO 7621 05:42:02,446 --> 05:42:07,184 POINT OUT THE CHALLENGE. 7622 05:42:07,184 --> 05:42:11,255 IF YOU LOOK AT THE TABLE ON THE 7623 05:42:11,255 --> 05:42:12,956 RIGHT YOU'LL SEE A THIRD OF 7624 05:42:12,956 --> 05:42:14,758 PATIENTS REQUIRE THREE CYCLES 7625 05:42:14,758 --> 05:42:18,362 AND MOBILIZATION AND COLLECTION 7626 05:42:18,362 --> 05:42:23,100 TO GENERATE A PRODUCT. 7627 05:42:23,100 --> 05:42:24,501 AND THAT MEANS GOING TO THE 7628 05:42:24,501 --> 05:42:26,103 HOSPITAL, STAYING SEVERAL DAYS, 7629 05:42:26,103 --> 05:42:28,372 COLLECTING CELLS, WAITING FOR AN 7630 05:42:28,372 --> 05:42:30,707 ANSWER AND FOR MOST COMING BACK 7631 05:42:30,707 --> 05:42:32,242 ANOTHER MONTH LATER AND MAYBE 7632 05:42:32,242 --> 05:42:33,177 REPEATING THAT ANOTHER MONTH. 7633 05:42:33,177 --> 05:42:34,745 THAT'S A WAITING PERIOD THAT WE 7634 05:42:34,745 --> 05:42:39,817 HAVE TO IMPROVE ON. 7635 05:42:39,817 --> 05:42:42,519 HOW DO WE IDENTIFY WHO WOULD BE 7636 05:42:42,519 --> 05:42:52,930 AT RISK FOR COLLECTION? 7637 05:42:54,998 --> 05:42:57,134 HALF THE PATIENTS REQUIRE 7638 05:42:57,134 --> 05:42:58,702 MULTIPLE SAMPLES FOR COLLECTION. 7639 05:42:58,702 --> 05:43:04,775 THIS IS FOR ALL TOGETHER. 7640 05:43:04,775 --> 05:43:06,944 IF YOU THINK ABOUT THE PATIENTS 7641 05:43:06,944 --> 05:43:08,512 AND WE HAVE EXPERTS AND 7642 05:43:08,512 --> 05:43:13,383 FANTASTIC PUBLICATIONS AND 7643 05:43:13,383 --> 05:43:22,860 EXPERTS IN THE ROOM SHOWING HOW 7644 05:43:22,860 --> 05:43:27,631 YOU APPROACH IN OTHER WORDS THE 7645 05:43:27,631 --> 05:43:30,501 MORE YOU HAVE GOING ON BECAUSE 7646 05:43:30,501 --> 05:43:32,503 SICKLE CELL DISEASE THE LESS 7647 05:43:32,503 --> 05:43:35,072 YOU'LL MOBILIZE WELL AND IMPACT. 7648 05:43:35,072 --> 05:43:36,740 IT WASN'T APPRECIATED. 7649 05:43:36,740 --> 05:43:40,377 I MAY SEEM OBVIOUS BUT THAT WORK 7650 05:43:40,377 --> 05:43:46,116 IS HIGHLY, HIGHLY IMPACTFUL. 7651 05:43:46,116 --> 05:43:48,986 SO CONSIDER IMPROVING OVER ALL 7652 05:43:48,986 --> 05:43:51,121 DISEASE AND RED CELL EXCHANGE IS 7653 05:43:51,121 --> 05:43:52,890 ENOUGH AND RED CELL CHANGE MAY 7654 05:43:52,890 --> 05:43:55,792 BE USED AND THOUGHT ABOUT AS A 7655 05:43:55,792 --> 05:43:57,628 THERAPEUTIC TOOL AND THE WORKING 7656 05:43:57,628 --> 05:44:04,801 GROUP HELPED PINPOINT THAT. 7657 05:44:04,801 --> 05:44:06,503 WE UNDERSTAND TECHNICAL 7658 05:44:06,503 --> 05:44:09,072 INTERRUPTIONS AFFECTED OUTCOME. 7659 05:44:09,072 --> 05:44:11,175 IF YOU'RE DOING A COLLECTION 7660 05:44:11,175 --> 05:44:12,476 THAT TAKES HOURS ALL THE 7661 05:44:12,476 --> 05:44:13,210 INTERRUPTIONS DURING THE TIME 7662 05:44:13,210 --> 05:44:15,379 YOU MAY FORGET ABOUT THEM BUT 7663 05:44:15,379 --> 05:44:22,553 TAKE THEM TOGETHER THAT MAY HAVE 7664 05:44:22,553 --> 05:44:22,786 IMPACT. 7665 05:44:22,786 --> 05:44:24,454 SELECTING THE INTERFACE. 7666 05:44:24,454 --> 05:44:28,859 THAT'S VERY GRANULAR TALK FOR 7667 05:44:28,859 --> 05:44:30,494 HOW WE'RE PROGRAMMING THE 7668 05:44:30,494 --> 05:44:33,030 INSTRUMENT BUT IT'S INCREDIBLY 7669 05:44:33,030 --> 05:44:36,800 IMPORTANT REQUIRES TRAINING AND 7670 05:44:36,800 --> 05:44:38,168 VASCULAR ACCESS AND PATIENT 7671 05:44:38,168 --> 05:44:45,409 ACCESS NEEDS TO BE STANDARDIZED. 7672 05:44:45,409 --> 05:44:46,243 RECURRING THEMES THAT'S PRACTICE 7673 05:44:46,243 --> 05:44:46,543 VARIABILITY. 7674 05:44:46,543 --> 05:44:53,016 I POINTED TO THE POINTS ON THE 7675 05:44:53,016 --> 05:44:54,518 SLIDE. 7676 05:44:54,518 --> 05:44:56,119 THIS WILL BE ONLINE AND THERE'S 7677 05:44:56,119 --> 05:44:59,356 A CHECKLIST SOMEBODY SHOULD HAVE 7678 05:44:59,356 --> 05:45:01,124 AND WHO THAT SOMEBODY IS MAY 7679 05:45:01,124 --> 05:45:02,459 VARY AT INSTITUTIONS AND THAT'S 7680 05:45:02,459 --> 05:45:09,800 SOMETHING ELSE THE WORKING GROUP 7681 05:45:09,800 --> 05:45:12,836 LOOKED AT A DIFFERENT APHERESIS 7682 05:45:12,836 --> 05:45:14,605 PROVIDER. 7683 05:45:14,605 --> 05:45:17,975 SOMETIMES TRANSPLANT, SOMETIMES 7684 05:45:17,975 --> 05:45:19,977 HEMATOLOGY AND TRANSFUSION OR 7685 05:45:19,977 --> 05:45:21,945 LABORATORY MEDICINE OR PATHOLOGY 7686 05:45:21,945 --> 05:45:27,951 AND HAVE TO INSURRECT AND I'M 7687 05:45:27,951 --> 05:45:29,853 THE ONE THAT WANTS TO PUT 7688 05:45:29,853 --> 05:45:32,122 APHERESIS IN THE MIDDLE OF THAT 7689 05:45:32,122 --> 05:45:35,859 BECAUSE THERE'S A LONG PERIOD OF 7690 05:45:35,859 --> 05:45:37,494 TIME WHERE YOU HAVE TO BE TRANS 7691 05:45:37,494 --> 05:45:40,330 FUSING AND HAVE TO THINK ABOUT 7692 05:45:40,330 --> 05:45:41,198 RED CELL EXCHANGE AND THINK 7693 05:45:41,198 --> 05:45:42,432 ABOUT THE COLLECTION. 7694 05:45:42,432 --> 05:45:46,203 WHO IS COORDINATING THAT AND 7695 05:45:46,203 --> 05:45:47,204 SEEING THE PATIENT. 7696 05:45:47,204 --> 05:45:52,476 YOU HAVE TO INVOLVE THE 7697 05:45:52,476 --> 05:45:58,282 CARETAKER IN THE PROCESS. 7698 05:45:58,282 --> 05:46:02,686 SO REGIMENTS TO STABILIZE VOEs 7699 05:46:02,686 --> 05:46:06,590 TO REDUCE ERYTHROHYPERPLASIA AND 7700 05:46:06,590 --> 05:46:08,525 SOMETHING WE HAVE TO UNDERSTAND 7701 05:46:08,525 --> 05:46:10,160 AND STUDY. 7702 05:46:10,160 --> 05:46:12,496 CAN RED CELL EXCHANGE IMPROVE 7703 05:46:12,496 --> 05:46:15,332 THE HEALTH OF A BONE MARROW. 7704 05:46:15,332 --> 05:46:23,307 THOUGH WE COULD DO THE STUDYUND. 7705 05:46:23,307 --> 05:46:23,907 CAN RED CELL EXCHANGE IMPROVE 7706 05:46:23,907 --> 05:46:24,474 THE HEALTH OF A BONE MARROW. 7707 05:46:24,474 --> 05:46:25,108 THOUGH WE COULD DO THE STUDY WOE 7708 05:46:25,108 --> 05:46:27,678 DON'T KNOW IF IT'S THE CASE IN 7709 05:46:27,678 --> 05:46:28,011 PATIENTS. 7710 05:46:28,011 --> 05:46:29,913 IS THE ROLE SIMPLY TO PROTECT 7711 05:46:29,913 --> 05:46:32,749 PATIENTS DURING THE PERIOD WHEN 7712 05:46:32,749 --> 05:46:38,588 THEY'RE OFF THEIR USUAL 7713 05:46:38,588 --> 05:46:41,958 MEDICATIONS THAT PROTECT THEM 7714 05:46:41,958 --> 05:46:45,262 FROM VASO OCCLUSIVE CRISIS BUT 7715 05:46:45,262 --> 05:46:46,363 WE SHOULD THINK THERAPEUTICALLY. 7716 05:46:46,363 --> 05:46:48,965 THE ACTIVITIES REQUIRE DATA 7717 05:46:48,965 --> 05:46:53,337 COLLECTION ASSESSMENT SO THE 7718 05:46:53,337 --> 05:46:54,104 REGISTRIES WE'RE DISCUSSING POST 7719 05:46:54,104 --> 05:46:56,139 TRANSPLANT WE HAVE TO THINK 7720 05:46:56,139 --> 05:47:02,546 ABOUT WHAT DO WE TAKE AS INTAKE 7721 05:47:02,546 --> 05:47:03,947 BEFORE TRANSPLANTATION BEFORE 7722 05:47:03,947 --> 05:47:05,349 GENE THERAPY FOR OUTCOMES FOR 7723 05:47:05,349 --> 05:47:15,025 MOBILIZATION AND COLLECTION. 7724 05:47:15,025 --> 05:47:20,864 THIS IS SHOWING IN THE GRASP 7725 05:47:20,864 --> 05:47:24,034 TRIAL FUNDED THERE'S MANY SWIM 7726 05:47:24,034 --> 05:47:26,203 LANES AND YOU SEE SWIM LANE 7727 05:47:26,203 --> 05:47:27,637 AFTER SWIM LANE OF WHAT NEEDS TO 7728 05:47:27,637 --> 05:47:28,839 BE DONE WITH PATIENTS BEFORE 7729 05:47:28,839 --> 05:47:30,507 THEY GET TRANSPLANTED. 7730 05:47:30,507 --> 05:47:31,675 AND THERE'S A LOT THERE. 7731 05:47:31,675 --> 05:47:39,950 THAT NEEDS TO BE COORDINATED. 7732 05:47:39,950 --> 05:47:47,023 ANOTHER THING WE UNDERSTOOD IN 7733 05:47:47,023 --> 05:47:51,795 THE WORKING GROUP FOR THE 7734 05:47:51,795 --> 05:48:02,272 COMMUNITY IS THAT PLERRI -- 7735 05:48:13,650 --> 05:48:14,351 PLERIXAFOR AND YOU SEE THE DATA 7736 05:48:14,351 --> 05:48:18,555 PUBLISHED. 7737 05:48:18,555 --> 05:48:24,728 THE MANUSCRIPT WITH THE DATA 7738 05:48:24,728 --> 05:48:27,564 SHOWING A HUGE VARIATION IN 7739 05:48:27,564 --> 05:48:28,265 COLLECTION EFFICIENCY. 7740 05:48:28,265 --> 05:48:31,301 THIS IS HOW MANY CELLS WE CAN 7741 05:48:31,301 --> 05:48:33,170 GET TO FOR THE APHERESIS LEVEL 7742 05:48:33,170 --> 05:48:39,075 AS A METRIC AND IT GOES FROM 10 7743 05:48:39,075 --> 05:48:40,510 TO 100 AND THAT'S BOSTON 7744 05:48:40,510 --> 05:48:41,344 CHILDREN'S. 7745 05:48:41,344 --> 05:48:43,447 WE CAN SEE A WIDE VARIATION. 7746 05:48:43,447 --> 05:48:45,282 WE HAVE TO UNDERSTAND WE WANT 7747 05:48:45,282 --> 05:48:48,318 SOMETHING AT 40% OR GREATER AND 7748 05:48:48,318 --> 05:48:49,386 IF YOU'RE GETTING MANY PATIENTS 7749 05:48:49,386 --> 05:48:51,955 THAT AREN'T, WHO IS THAT PATIENT 7750 05:48:51,955 --> 05:48:57,961 CAN WE PREDICT THAT AND THE 7751 05:48:57,961 --> 05:49:08,171 BIOMARK 7752 05:49:18,849 --> 05:49:21,985 BIOMARKERS AND LOOK AT THEM AND 7753 05:49:21,985 --> 05:49:22,819 SEE EXACTLY WHAT WE'RE DOING 7754 05:49:22,819 --> 05:49:33,330 WITH THE INSTRUMENT OVER TIME. 7755 05:49:35,031 --> 05:49:38,034 SO THIS NEEDS TO BE STUDIED. 7756 05:49:38,034 --> 05:49:39,536 BRINGING SOMEBODY IN AND HAVING 7757 05:49:39,536 --> 05:49:40,370 A WAITING PERIOD BEFORE THEY ARE 7758 05:49:40,370 --> 05:49:44,674 GO ON, DOCUMENTING A FULL BLOOD 7759 05:49:44,674 --> 05:49:45,375 BANK HISTORY. 7760 05:49:45,375 --> 05:49:47,477 HEMOGLOBIN TARGET OF 30% BEFORE 7761 05:49:47,477 --> 05:49:49,145 YOU START MOBILIZATION AND 7762 05:49:49,145 --> 05:49:51,548 DURING THE TIME PERIOD AGAIN 7763 05:49:51,548 --> 05:49:54,551 YOU'RE DOING TRANSFUSION BEFORE 7764 05:49:54,551 --> 05:49:58,088 YOU MOBILIZE AND PERHAPS WHILE 7765 05:49:58,088 --> 05:49:59,022 YOU'RE MAKING A GENE THERAPY 7766 05:49:59,022 --> 05:50:08,498 TRIAL. 7767 05:50:08,498 --> 05:50:10,867 VASCULAR ACCESS TO TRANSFUSION. 7768 05:50:10,867 --> 05:50:13,403 SO AGAIN IMPROVING MOBILIZATION, 7769 05:50:13,403 --> 05:50:16,139 IMPROVING THE UNDERLYING 7770 05:50:16,139 --> 05:50:16,373 DISEASE. 7771 05:50:16,373 --> 05:50:17,340 I THINK WE MADE THAT CLEAR 7772 05:50:17,340 --> 05:50:24,881 THROUGH THE SLIDES. 7773 05:50:24,881 --> 05:50:26,383 OTHER RECOMMENDATIONS AS A 7774 05:50:26,383 --> 05:50:29,853 WORKING GROUP, TARGETING HPC 7775 05:50:29,853 --> 05:50:32,856 CELLS AND PROGENITOR CELLS AT A 7776 05:50:32,856 --> 05:50:33,189 DEEPER LAYER. 7777 05:50:33,189 --> 05:50:39,863 I THINK WE'VE BEEN ABLE TO 7778 05:50:39,863 --> 05:50:41,031 COMMUNICATE THIS THROUGH THE 7779 05:50:41,031 --> 05:50:45,135 COLLECTIONS. 7780 05:50:45,135 --> 05:50:50,006 AND THIS NOW PART OF THE 7781 05:50:50,006 --> 05:50:52,008 EDUCATION AROUND THERAPIES AND 7782 05:50:52,008 --> 05:50:53,910 THIS MAY SEEM GRANULAR BUT THE 7783 05:50:53,910 --> 05:50:56,947 TAKE HOME MESSAGE IS IT'S NOT A 7784 05:50:56,947 --> 05:50:58,982 REGULAR STEM CELL PRODUCTION. 7785 05:50:58,982 --> 05:51:02,686 SO GO TO YOUR EXPERTISE, CONTACT 7786 05:51:02,686 --> 05:51:05,622 A CENTER THAT KNOWS HOW TO 7787 05:51:05,622 --> 05:51:10,894 COLLECT STEM CELLS AND ALSO 7788 05:51:10,894 --> 05:51:12,362 ASKING THE COMMERCIAL 7789 05:51:12,362 --> 05:51:13,496 MANUFACTURERS TO MAKE SURE 7790 05:51:13,496 --> 05:51:16,499 THEY'RE USING THESE 7791 05:51:16,499 --> 05:51:25,542 RECOMMENDATIONS. 7792 05:51:25,542 --> 05:51:30,280 UNDERSTANDING THE COLLECTION AND 7793 05:51:30,280 --> 05:51:34,918 THE NEED FOR MORE. 7794 05:51:34,918 --> 05:51:36,386 VASCULAR ACCESS. 7795 05:51:36,386 --> 05:51:38,088 WE NEED THE TAKE HOME MESSAGE OF 7796 05:51:38,088 --> 05:51:43,927 THE SLIDE IS YOU DO NEED VESS 7797 05:51:43,927 --> 05:51:45,195 -- VASCULAR ACCESS. 7798 05:51:45,195 --> 05:51:47,664 IT'S NOT STUDIED ENOUGH. 7799 05:51:47,664 --> 05:51:49,699 WE DON'T HAVE MANUFACTURERS OF 7800 05:51:49,699 --> 05:51:52,235 IMPLANTED VASCULAR DEVICES TO BE 7801 05:51:52,235 --> 05:51:54,971 ABLE TO DO RED CELL EXCHANGE, 7802 05:51:54,971 --> 05:51:56,473 TRANSFUSION. 7803 05:51:56,473 --> 05:51:59,643 THIS IS NOT REALLY TELLING FOR 7804 05:51:59,643 --> 05:52:01,044 THE SICKLE CELL COMMUNITY THE 7805 05:52:01,044 --> 05:52:04,280 PATIENTS WITH SICKLE CELL AND WE 7806 05:52:04,280 --> 05:52:10,854 HAVE TO THINK ABOUT THIS IN THE 7807 05:52:10,854 --> 05:52:12,322 HEMATOPOIESIS AND STUDY IN A 7808 05:52:12,322 --> 05:52:12,956 BROADER LEVEL. 7809 05:52:12,956 --> 05:52:14,024 FUTURE DIRECTIONS FOR 7810 05:52:14,024 --> 05:52:14,758 TRANSFUSION MEDICINE. 7811 05:52:14,758 --> 05:52:17,661 THIS IS ONE OF MY LAST SLIDES. 7812 05:52:17,661 --> 05:52:19,629 WE NEED TO IMPROVE THE 7813 05:52:19,629 --> 05:52:22,365 CHALLENGES BECAUSE IF THIS 7814 05:52:22,365 --> 05:52:24,601 BOTTLENECK OF BEING ABLE TO 7815 05:52:24,601 --> 05:52:28,505 COLLECT ENOUGH CELLS TO TAKE 7816 05:52:28,505 --> 05:52:30,407 PATIENTS THROUGH THE JOURNEY IF 7817 05:52:30,407 --> 05:52:32,776 WE DON'T IMPROVE THIS, WE'RE NOT 7818 05:52:32,776 --> 05:52:35,345 ONLY DOING A DISSERVICE TO THE 7819 05:52:35,345 --> 05:52:36,780 PATIENTS WE CAN'T GET THE 7820 05:52:36,780 --> 05:52:38,181 THERAPY TO THE MANY PATIENTS 7821 05:52:38,181 --> 05:52:38,882 THAT NEED IT. 7822 05:52:38,882 --> 05:52:46,456 AND WHAT I MEAN BY THAT IS NOT 7823 05:52:46,456 --> 05:52:49,059 ONLY PATIENTS WORLDWIDE BUT HALF 7824 05:52:49,059 --> 05:52:52,529 LIFE STUDIES THAT WERE 7825 05:52:52,529 --> 05:52:53,463 BEAUTIFULLY SHOWN THIS MORNING 7826 05:52:53,463 --> 05:52:56,399 ALL PART OF THE TRANSFUSION TO 7827 05:52:56,399 --> 05:52:59,769 IMPROVE RED CELL EXCHANGE, 7828 05:52:59,769 --> 05:53:00,970 EDUCATION AROUND GENE THERAPY AS 7829 05:53:00,970 --> 05:53:02,605 BROUGHT UP AND WHAT CELLS WE'RE 7830 05:53:02,605 --> 05:53:04,874 COLLECTING. 7831 05:53:04,874 --> 05:53:08,178 HOW CAN WE PARTNER AND BE ABLE 7832 05:53:08,178 --> 05:53:11,614 TO DO THIS. 7833 05:53:11,614 --> 05:53:13,750 AND REALLY NEXT GENERATION FOR 7834 05:53:13,750 --> 05:53:15,685 IN VIVO HOW DOES APHERESIS 7835 05:53:15,685 --> 05:53:16,820 PARTNER WITH THAT. 7836 05:53:16,820 --> 05:53:19,289 THE WHITE PAPER WILL BE COMING 7837 05:53:19,289 --> 05:53:20,190 OUT AND HOPEFULLY THEY'LL GIVE 7838 05:53:20,190 --> 05:53:24,894 MORE INSIGHTS. 7839 05:53:24,894 --> 05:53:27,297 AN ACKNOWLEDGEMENT TO THE 7840 05:53:27,297 --> 05:53:32,502 WORKING GROUP ON THE BOTTOM 7841 05:53:32,502 --> 05:53:43,012 RIGHT TIRELESS WORK DONE AND 7842 05:53:44,948 --> 05:53:49,285 UNDERSTAND APHERESIS WAS 7843 05:53:49,285 --> 05:53:50,687 IMPORTANT AND TO TAKE THIS OUT 7844 05:53:50,687 --> 05:53:51,054 TO PUBLICATION. 7845 05:53:51,054 --> 05:53:58,995 THANK YOU. 7846 05:53:58,995 --> 05:54:01,264 >> WE DO HAVE A FEW MINUTES FOR 7847 05:54:01,264 --> 05:54:01,631 ANY QUESTIONS. 7848 05:54:01,631 --> 05:54:02,632 ARE THERE QUESTIONS ONLINE OR IN 7849 05:54:02,632 --> 05:54:12,709 THE AUDIENCE? 7850 05:54:12,709 --> 05:54:16,513 ALL RIGHT. 7851 05:54:16,513 --> 05:54:26,790 MOVING FORWARD. 7852 05:54:33,429 --> 05:54:35,098 >> SO WE ARE VERY EXCITED TO BE 7853 05:54:35,098 --> 05:54:40,503 HERE AND THANK YOU TO THE O 7854 05:54:40,503 --> 05:54:42,372 ORGIORG 7855 05:54:42,372 --> 05:54:46,843 ORGANIZERS FOR INVITING US FOR 7856 05:54:46,843 --> 05:54:47,377 THE SICKLE CELL DISEASE 7857 05:54:47,377 --> 05:54:48,244 INITIATIVE AND TALK ABOUT THE 7858 05:54:48,244 --> 05:54:55,285 WORKING GROUP AND SOME UPDATES. 7859 05:54:55,285 --> 05:54:58,888 >> I'M GOING TO CHECK CAN ANYONE 7860 05:54:58,888 --> 05:55:00,423 HEAR ME? 7861 05:55:00,423 --> 05:55:01,357 >> YES. 7862 05:55:01,357 --> 05:55:02,759 >> IT'S NICE TO BE HERE. 7863 05:55:02,759 --> 05:55:05,528 SAD I COULD NOT BE THERE IN 7864 05:55:05,528 --> 05:55:05,762 PERSON. 7865 05:55:05,762 --> 05:55:07,096 UNFORTUNATELY THINGS DO HAPPEN. 7866 05:55:07,096 --> 05:55:09,632 BUT VERY EXCITED TO BE ABLE TO 7867 05:55:09,632 --> 05:55:11,601 TALK ABOUT THIS TOPIC OF WHAT 7868 05:55:11,601 --> 05:55:13,203 OUR GROUP HAS BEEN FOCUSSED ON 7869 05:55:13,203 --> 05:55:15,972 FOR THE PAST NUMBER OF YEARS. 7870 05:55:15,972 --> 05:55:18,608 I THINK IT'S VERY IN LINE WITH 7871 05:55:18,608 --> 05:55:19,843 THE PREVIOUS TALKS PARTICULARLY 7872 05:55:19,843 --> 05:55:21,811 THE PANEL AND I APPRECIATE THE 7873 05:55:21,811 --> 05:55:26,249 YOUNG WOMAN WHO SPOKE ABOUT HER 7874 05:55:26,249 --> 05:55:27,617 EXPERIENCE AND DECISION POINTS 7875 05:55:27,617 --> 05:55:29,652 AND THINKING ABOUT GENE THERAPY 7876 05:55:29,652 --> 05:55:31,254 AND I THINK THAT'S BEEN ONE OF 7877 05:55:31,254 --> 05:55:36,492 THE STARTING POINTS FOR OUR 7878 05:55:36,492 --> 05:55:40,797 GROUP AND TEAM. 7879 05:55:40,797 --> 05:55:41,998 I'M NOT GOING TO SPEND AS MUCH 7880 05:55:41,998 --> 05:55:43,900 AS TIME AS I USUALLY DO TALKING 7881 05:55:43,900 --> 05:55:45,735 ABOUT THE CASE AGAINST OR THE 7882 05:55:45,735 --> 05:55:47,537 CASE FOR READINESS BECAUSE I 7883 05:55:47,537 --> 05:55:50,039 THINK A LARGE PART OF THE 7884 05:55:50,039 --> 05:55:50,940 CONVERSATION WE'VE BEEN HAVING 7885 05:55:50,940 --> 05:55:52,709 HAS HELPED TO MAKE THE CASE. 7886 05:55:52,709 --> 05:55:56,012 I WILL GO AHEAD AND PRESENT OUR 7887 05:55:56,012 --> 05:55:58,248 SIMULATED CASE STUDY A 7888 05:55:58,248 --> 05:56:02,285 19-YEAR-OLD FEMALE WITH-BSS WHO 7889 05:56:02,285 --> 05:56:04,153 HAD SIGNIFICANT COMPLICATIONS 7890 05:56:04,153 --> 05:56:13,162 AND REPEATED VOC AND ACS EVENTS 7891 05:56:13,162 --> 05:56:14,297 AND DEVELOPED CHRONIC PAIN AND 7892 05:56:14,297 --> 05:56:16,432 MAINTAINS FAIRLY ACTIVE 7893 05:56:16,432 --> 05:56:17,600 LIFESTYLE AND DOES WELL IN 7894 05:56:17,600 --> 05:56:19,969 SCHOOL AND DREAMS OF HAVING A 7895 05:56:19,969 --> 05:56:21,504 FAMILY AND BEING A HEMATOLOGIST. 7896 05:56:21,504 --> 05:56:24,474 HER FAMILY IS STRONGLY 7897 05:56:24,474 --> 05:56:27,210 ADVOCATING FOR HER TO PURSUE A 7898 05:56:27,210 --> 05:56:28,578 CURATIVE THERAPY. 7899 05:56:28,578 --> 05:56:30,813 HER FATHER COMMENTED NO MAN WILL 7900 05:56:30,813 --> 05:56:38,621 WANT TO MARRY HER UNLESS SHE 7901 05:56:38,621 --> 05:56:43,760 GETS THE TREATMENT AND DECIDES 7902 05:56:43,760 --> 05:56:47,597 TO PROCEED WITH THE WORKUP FOR 7903 05:56:47,597 --> 05:56:48,898 GENE THERAPY. 7904 05:56:48,898 --> 05:56:52,835 WE'RE FOCUSSED ON ALL OF OUR 7905 05:56:52,835 --> 05:56:59,275 UNDERLYING MEDICAL TESTS BUT AS 7906 05:56:59,275 --> 05:57:00,777 HAS BEEN NICELY HIGHLIGHTED THIS 7907 05:57:00,777 --> 05:57:02,979 IS A PERSON IN THE SPACE OF 7908 05:57:02,979 --> 05:57:03,613 FIGHTING SICKLE CELL DISEASE AND 7909 05:57:03,613 --> 05:57:05,048 THERE'S OTHER CONCERNS THAT GO 7910 05:57:05,048 --> 05:57:10,553 TO THE DECISION PARTICULARLY ON 7911 05:57:10,553 --> 05:57:14,991 THE PATIENT SIDE THAT NEED TO BE 7912 05:57:14,991 --> 05:57:16,693 TAKEN INTO ACCOUNT. 7913 05:57:16,693 --> 05:57:18,661 SOME ARE GOING TO BE EVERYTHING 7914 05:57:18,661 --> 05:57:20,964 FROM DEVELOPMENTALLY WHERE THE 7915 05:57:20,964 --> 05:57:25,068 PERSON IS TO WITHIN THEIR OWN 7916 05:57:25,068 --> 05:57:28,204 SPAN AND ARE WE TALKING ABOUT 7917 05:57:28,204 --> 05:57:29,605 PEDIATRIC OR ADULT OR SOMEONE 7918 05:57:29,605 --> 05:57:32,075 INTERESTED IN HAVING CHILDREN OR 7919 05:57:32,075 --> 05:57:33,810 DEEPLY EMBEDDED WITHIN THE 7920 05:57:33,810 --> 05:57:36,512 SICKLE CELL COMMUNITY? 7921 05:57:36,512 --> 05:57:38,481 ABOUT WHAT ARE TO THE PERSON'S 7922 05:57:38,481 --> 05:57:40,950 INDIVIDUAL SAFETY CONCERNS AND 7923 05:57:40,950 --> 05:57:41,684 PSYCHOSOCIAL RISK WITH RISK TO 7924 05:57:41,684 --> 05:57:44,253 EMPLOYMENT AND OTHER THINGS. 7925 05:57:44,253 --> 05:57:46,322 AND DECIDING TO PARTICIPATE OR 7926 05:57:46,322 --> 05:57:48,057 NOT PARTICIPATE IN CLINICAL 7927 05:57:48,057 --> 05:57:48,725 TRIAL FOR GENE THERAPY IS NOT A 7928 05:57:48,725 --> 05:57:54,230 SIMPLE DECISION. 7929 05:57:54,230 --> 05:57:56,432 AND HIGHLIGHT PSYCHOSOCIAL 7930 05:57:56,432 --> 05:57:57,633 FACTORS WILL INFLUENCE A 7931 05:57:57,633 --> 05:57:59,435 PERSON'S READINESS FOR GENE 7932 05:57:59,435 --> 05:58:00,370 THERAPY AND TREATMENT OUTCOMES 7933 05:58:00,370 --> 05:58:03,206 ON THE OTHER SIDE WILL IMPACT A 7934 05:58:03,206 --> 05:58:05,341 PERSON'S PSYCHOSOCIAL WELL BEING 7935 05:58:05,341 --> 05:58:06,542 IN THE SHORT AND LONG-TERM 7936 05:58:06,542 --> 05:58:08,511 WHETHER THEY'RE POSITIVE OR 7937 05:58:08,511 --> 05:58:10,246 NEGATIVE OR NOT WHAT WAS 7938 05:58:10,246 --> 05:58:11,280 ORIGINALLY EXPECTED WHEN THEY 7939 05:58:11,280 --> 05:58:15,451 SIGNED UP FOR GENE THERAPY. 7940 05:58:15,451 --> 05:58:17,487 NOW, WITH OUR TEAM AND WHAT'S 7941 05:58:17,487 --> 05:58:19,055 BEEN AN IMPORTANT PIECE FOR US 7942 05:58:19,055 --> 05:58:22,625 IS WE HAVE BEEN CREATING AND 7943 05:58:22,625 --> 05:58:24,927 GOING OVER GUIDELINES SPECIFIC 7944 05:58:24,927 --> 05:58:27,196 FOR ALL THE MEDICAL PIECES WHEN 7945 05:58:27,196 --> 05:58:29,932 IT COMES TO RADIOLOGY AND 7946 05:58:29,932 --> 05:58:31,567 CARDIOLOGY AND ALL THOSE PIECES 7947 05:58:31,567 --> 05:58:33,569 IN RELATION TO BEING REPAIRED 7948 05:58:33,569 --> 05:58:35,038 FOR GENE THERAPY AND THERE 7949 05:58:35,038 --> 05:58:38,274 SHOULD BE A STANDARDIZED WAY OF 7950 05:58:38,274 --> 05:58:41,277 ALSO THINKING ABOUT THE 7951 05:58:41,277 --> 05:58:42,645 PSYCHOSOCIAL, PSYCHOLOGICAL 7952 05:58:42,645 --> 05:58:44,047 SPIRITUAL AND CULTURAL FACTORS 7953 05:58:44,047 --> 05:58:49,018 SO WE CAN BOTH MAKE SURE THE 7954 05:58:49,018 --> 05:58:54,090 PATIENT IS FULLY INFORMED AND 7955 05:58:54,090 --> 05:58:56,192 OPTIMIZE BENEFITS MEDICALLY AND 7956 05:58:56,192 --> 05:58:56,793 PSYCHOSOCIALLY THROUGHOUT THE 7957 05:58:56,793 --> 05:59:00,630 PROCESS. 7958 05:59:00,630 --> 05:59:02,265 SO THIS IS THE GUIDING QUESTION 7959 05:59:02,265 --> 05:59:06,469 OUR GROUP HAS GRAPPLED WITH. 7960 05:59:06,469 --> 05:59:07,170 IF A PERSON WITH SICKLE CELL 7961 05:59:07,170 --> 05:59:09,205 DISEASE CHOOSE TO PARTICIPATE IN 7962 05:59:09,205 --> 05:59:10,273 CLINICAL TRIAL WHAT LEVEL OF 7963 05:59:10,273 --> 05:59:13,142 PSYCHOSOCIAL SUPPORT IS NEEDED 7964 05:59:13,142 --> 05:59:15,578 TO MINIMIZE RISK OF PSYCHOSOCIAL 7965 05:59:15,578 --> 05:59:17,947 BURDEN AND OPTIMIZE BENEFITS? 7966 05:59:17,947 --> 05:59:18,681 THINKING ABOUT THIS THROUGHOUT 7967 05:59:18,681 --> 05:59:21,350 THE ENTIRE COURSE OF TREATMENT 7968 05:59:21,350 --> 05:59:22,418 BOTH BEFORE WHEN THE PERSON IS 7969 05:59:22,418 --> 05:59:23,519 MAKING THE DECISION AS TO 7970 05:59:23,519 --> 05:59:26,789 WHETHER OR NOT TO BE A PART OF 7971 05:59:26,789 --> 05:59:28,991 THE GENE THERAPY CLINICAL TRIAL 7972 05:59:28,991 --> 05:59:31,394 DURING WHICH A LONG AND ARDUOUS 7973 05:59:31,394 --> 05:59:32,328 AND AFTER. 7974 05:59:32,328 --> 05:59:36,499 THINKING ABOUT THE 15 YEARS OF 7975 05:59:36,499 --> 05:59:38,134 CONTINUOUS FOLLOW-UP FROM THE 7976 05:59:38,134 --> 05:59:39,102 HEALTH CARE TEAM AND POSSIBLY 7977 05:59:39,102 --> 05:59:40,736 THE REST OF THEIR LIVES THINKING 7978 05:59:40,736 --> 05:59:43,039 ABOUT THE CONSEQUENCES GOING 7979 05:59:43,039 --> 05:59:44,607 THROUGH A TRANSFORMATIVE THERAPY 7980 05:59:44,607 --> 05:59:50,313 CAN HAVE. 7981 05:59:50,313 --> 05:59:53,116 NOW AT THIS POINT I'M GOING TO 7982 05:59:53,116 --> 05:59:56,052 TALK HOW WE HANDLED THIS FOR 7983 05:59:56,052 --> 05:59:59,255 THINGS WE CONSIDER ARE PHASE 1. 7984 05:59:59,255 --> 06:00:04,026 I'M GOING TO GO TO MY CO-CHAIR, 7985 06:00:04,026 --> 06:00:06,295 DR. JERLYM PORTER AND TALK ABOUT 7986 06:00:06,295 --> 06:00:08,164 THE MORE CURRENT ACTIVITIES. 7987 06:00:08,164 --> 06:00:08,931 DR. PORTER. 7988 06:00:08,931 --> 06:00:17,340 >> THANK YOU. 7989 06:00:17,340 --> 06:00:19,642 SO THE INITIAL FOCUS OF THE 7990 06:00:19,642 --> 06:00:21,611 WORKING GROUP WAS TO OUTLINE A 7991 06:00:21,611 --> 06:00:24,480 WORK FLOW FOR INTEGRATING 7992 06:00:24,480 --> 06:00:25,615 PATIENT READINESS AND RESILIENCE 7993 06:00:25,615 --> 06:00:31,354 ASSESSMENT TO THERAPY 7994 06:00:31,354 --> 06:00:32,288 PROCEDURES. 7995 06:00:32,288 --> 06:00:35,158 WE CONCEPTUALIZE AS EXISTING ON 7996 06:00:35,158 --> 06:00:36,459 THE CONTINUUM AND FOCUS ON THE 7997 06:00:36,459 --> 06:00:39,128 DEVELOPMENT OF TWO AREAS OF 7998 06:00:39,128 --> 06:00:40,930 FOCUS OR BEST PRACTICES, 7999 06:00:40,930 --> 06:00:41,898 ASSESSING KNOWLEDGE AND 8000 06:00:41,898 --> 06:00:43,332 READINESS FOR GENE THERAPY OR 8001 06:00:43,332 --> 06:00:45,501 GENE EDITING CLINICAL TRIALS AND 8002 06:00:45,501 --> 06:00:49,605 ASSESSING PSYCHOSOCIAL RISK AND 8003 06:00:49,605 --> 06:00:51,707 PROTECTIVE FACTORS FROM THE 8004 06:00:51,707 --> 06:00:52,975 CONTEXT OF CLINICAL TRIALS. 8005 06:00:52,975 --> 06:00:56,245 YOU'LL SEE THE QR CODE TO THE 8006 06:00:56,245 --> 06:00:56,445 RIGHT. 8007 06:00:56,445 --> 06:01:00,183 THAT WILL SEND YOU TO OUR WHITE 8008 06:01:00,183 --> 06:01:01,617 PAPER ON THE CURE SICKLE CELL 8009 06:01:01,617 --> 06:01:02,451 INITIATIVE WEBSITE. 8010 06:01:02,451 --> 06:01:05,087 AND IF YOU DON'T SEE IT HERE, 8011 06:01:05,087 --> 06:01:10,793 YOU'LL SEE IT ON THE MENU 8012 06:01:10,793 --> 06:01:16,165 SLIDES. 8013 06:01:16,165 --> 06:01:21,871 AND THE PROCESS FOR TREATING TO 8014 06:01:21,871 --> 06:01:23,973 INTEGRATE PREGENE THERAPY AND 8015 06:01:23,973 --> 06:01:26,742 INSTITUTIONS ARE ENCOURAGED TO 8016 06:01:26,742 --> 06:01:28,811 BEGIN BY CONDUCTING A 8017 06:01:28,811 --> 06:01:30,646 SELF-ASSESSMENT FOR PREPAREDNESS 8018 06:01:30,646 --> 06:01:32,081 TO IMPLEMENT THE READINESS 8019 06:01:32,081 --> 06:01:33,916 ASSESSMENT AND TAKE STEPS NEEDED 8020 06:01:33,916 --> 06:01:35,885 TO ENHANCE PREPAREDNESS SUCH AS 8021 06:01:35,885 --> 06:01:38,187 HIRING STAFF OR IDENTIFYING 8022 06:01:38,187 --> 06:01:38,921 RESOURCES FOR TEMPORARY HOUSING 8023 06:01:38,921 --> 06:01:43,159 OR TRANSPORTATION. 8024 06:01:43,159 --> 06:01:46,062 STAGE 2 INVOLVES THE PATIENT 8025 06:01:46,062 --> 06:01:47,029 PREPARATION PHASE PRIOR TO 8026 06:01:47,029 --> 06:01:49,398 CONDUCTING THE READINESS 8027 06:01:49,398 --> 06:01:52,468 ASSESSMENT AND A BRIEF COGNITIVE 8028 06:01:52,468 --> 06:01:54,570 AND HEALTH LITERACY SCREENING TO 8029 06:01:54,570 --> 06:01:55,204 INFORM PATIENT EDUCATION ABOUT 8030 06:01:55,204 --> 06:02:00,076 GENE THERAPY. 8031 06:02:00,076 --> 06:02:01,811 PATIENT READINESS AND RESILIENCE 8032 06:02:01,811 --> 06:02:03,112 ASSESSMENT ARE PRIMARILY A 8033 06:02:03,112 --> 06:02:05,514 DISCUSSION OR CLINICAL INTERVIEW 8034 06:02:05,514 --> 06:02:08,184 BUT MAY BE COMPLIMENTED BY 8035 06:02:08,184 --> 06:02:09,919 VALIDATED QUESTIONNAIRES. 8036 06:02:09,919 --> 06:02:11,887 AND THE ASSESSMENTS ARE STAGE 3 8037 06:02:11,887 --> 06:02:13,422 OF OUR MODEL. 8038 06:02:13,422 --> 06:02:15,625 THESE ASSESSMENTS ARE 8039 06:02:15,625 --> 06:02:16,993 INFORMATIONAL FOR BOTH PATIENTS 8040 06:02:16,993 --> 06:02:19,395 AND INVESTIGATIVE TEAM AND USED 8041 06:02:19,395 --> 06:02:21,530 TO GUIDE THE DELIVERY OF 8042 06:02:21,530 --> 06:02:23,966 SUPPORTS TO ENHANCE PATIENT 8043 06:02:23,966 --> 06:02:24,233 READINESS. 8044 06:02:24,233 --> 06:02:25,534 IT'S IMPORTANT THAT THE 8045 06:02:25,534 --> 06:02:30,306 ASSESSMENT IS VIEWED AS HELPING 8046 06:02:30,306 --> 06:02:32,074 TO INFORM PATIENTS TREATMENT 8047 06:02:32,074 --> 06:02:33,209 DECISIONS AND THE ASSESSMENTS 8048 06:02:33,209 --> 06:02:36,178 SHOULD NEVER BE USED TO PLEASURE 8049 06:02:36,178 --> 06:02:39,749 OR PERSUADE A PATIENT TO PUBLIC 8050 06:02:39,749 --> 06:02:48,524 A DECISION OR NOT TO BE USED TO 8051 06:02:48,524 --> 06:02:50,293 PERMANENTLY PREVENT SEEKING A 8052 06:02:50,293 --> 06:02:51,861 FORM DESIRED. 8053 06:02:51,861 --> 06:02:55,698 OUR WORKING GROUP IDENTIFIED A 8054 06:02:55,698 --> 06:02:58,334 SET OF BEST PRACTICES SPANNING 8055 06:02:58,334 --> 06:03:01,304 FOUR BROAD ACTIVITIES. 8056 06:03:01,304 --> 06:03:07,143 SO SUPPORTING THE EFFECTIVE 8057 06:03:07,143 --> 06:03:16,485 DELIVERY OF -- EXCUSE ME. 8058 06:03:16,485 --> 06:03:17,753 THE FIVE OVER ARCHING GOALS OF 8059 06:03:17,753 --> 06:03:21,090 THE ASSESSMENTS ARE ONE, TO 8060 06:03:21,090 --> 06:03:23,826 GATHER INFORMATION ABOUT 8061 06:03:23,826 --> 06:03:24,694 PATIENT'S UNDERSTANDING AND 8062 06:03:24,694 --> 06:03:26,395 PERCEIVED READINESS OF GENE 8063 06:03:26,395 --> 06:03:28,331 THERAPY. 8064 06:03:28,331 --> 06:03:31,100 TWO, TO ENCOURAGE DIALOGUE 8065 06:03:31,100 --> 06:03:31,901 REGARDING CONCERNS ABOUT GENE 8066 06:03:31,901 --> 06:03:33,969 THERAPY AND THREE, PROVIDE AN 8067 06:03:33,969 --> 06:03:36,505 OVERVIEW OF FACTORS 8068 06:03:36,505 --> 06:03:38,974 AND AFFECT RELEVANT OUTCOMES. 8069 06:03:38,974 --> 06:03:40,710 FOUR, IDENTIFY PATIENT STRENGTHS 8070 06:03:40,710 --> 06:03:42,778 TO BE LEVERAGED TO PROMOTE 8071 06:03:42,778 --> 06:03:45,581 PSYCHOSOCIAL WELL BEING, BEFORE, 8072 06:03:45,581 --> 06:03:47,783 DURING AND AFTER TREATMENT AND 8073 06:03:47,783 --> 06:03:49,852 LASTLY TO IDENTIFY RISK TO BE 8074 06:03:49,852 --> 06:03:51,887 CONSIDERED AND ADDRESSED IN 8075 06:03:51,887 --> 06:03:54,924 TAILORED EDUCATION PSYCHOSOCIAL 8076 06:03:54,924 --> 06:04:00,696 SUPPORT AND COMMUNITY RESOURCES. 8077 06:04:00,696 --> 06:04:03,132 OUR WORKING GROUP IDENTIFY A SET 8078 06:04:03,132 --> 06:04:05,935 OF BEST PRACTICES FOR 8079 06:04:05,935 --> 06:04:06,802 RECOMMENDATIONS THAT SPAN FOUR 8080 06:04:06,802 --> 06:04:10,706 BROAD ACTIVITIES. 8081 06:04:10,706 --> 06:04:12,007 EFFECTIVELY DELIVERING 8082 06:04:12,007 --> 06:04:12,575 EDUCATION, ASSESSING 8083 06:04:12,575 --> 06:04:14,643 INDIVIDUAL'S KNOWLEDGE AND 8084 06:04:14,643 --> 06:04:17,179 UNDERSTANDING OF GENE THERAPY. 8085 06:04:17,179 --> 06:04:21,317 ALSO EVALUATING YOUR INTEREST IN 8086 06:04:21,317 --> 06:04:23,486 AN MOTIVATION FOR GENE THERAPY 8087 06:04:23,486 --> 06:04:25,488 AND EVALUATING AN INDIVIDUAL'S 8088 06:04:25,488 --> 06:04:29,525 PSYCHOSOCIAL RISK AND RESILIENCE 8089 06:04:29,525 --> 06:04:33,996 FACTORS THAT COULD INFLUENCE 8090 06:04:33,996 --> 06:04:35,698 PSYCHOSOCIAL WELL BEING AND 8091 06:04:35,698 --> 06:04:36,699 HEALTH BEFORE AND AFTER GENE 8092 06:04:36,699 --> 06:04:36,932 THERAPY. 8093 06:04:36,932 --> 06:04:39,001 AS I STATED EARLIER WE PUT 8094 06:04:39,001 --> 06:04:41,604 TOGETHER A WHITE PAPER THAT 8095 06:04:41,604 --> 06:04:44,607 OUTLINES THE EVIDENCE-BASED 8096 06:04:44,607 --> 06:04:45,408 STRATEGIES FOR PATIENT EDUCATION 8097 06:04:45,408 --> 06:04:47,777 AND HAVE ASSET TOOLS AND SAMPLE 8098 06:04:47,777 --> 06:04:52,481 INTERVIEW QUESTIONS. 8099 06:04:52,481 --> 06:04:59,655 SO PLEASE ACCESS THIS THROUGH 8100 06:04:59,655 --> 06:05:00,923 THE QR CODE. 8101 06:05:00,923 --> 06:05:02,491 FINAL THOUGHTS ON ASSESSING 8102 06:05:02,491 --> 06:05:03,826 PATIENT READINESS. 8103 06:05:03,826 --> 06:05:05,928 IT'S IMPORTANT TO ASSESS 8104 06:05:05,928 --> 06:05:06,929 READINESS AFTER EDUCATION ABOUT 8105 06:05:06,929 --> 06:05:10,366 GENE THERAPY AND ALLOW TIME FOR 8106 06:05:10,366 --> 06:05:14,670 RESULTS TO BE USEFUL. 8107 06:05:14,670 --> 06:05:16,705 THE INFORMATION CAN INFORM 8108 06:05:16,705 --> 06:05:21,710 INFORMED CONSENT AND PRESSURES 8109 06:05:21,710 --> 06:05:25,347 TO PARTICIPATE AND WHETHER 8110 06:05:25,347 --> 06:05:25,981 PSYCHOSOCIAL RISK SHOULD BE 8111 06:05:25,981 --> 06:05:27,516 ADDRESSED BEFORE MOVING FORWARD 8112 06:05:27,516 --> 06:05:29,952 IN TREATMENT. 8113 06:05:29,952 --> 06:05:31,353 READINESS AND RESILIENCE WILL 8114 06:05:31,353 --> 06:05:32,555 LOOK DIFFERENT IN EACH SETTING. 8115 06:05:32,555 --> 06:05:34,089 THE BEST PRACTICES ARE INTENDED 8116 06:05:34,089 --> 06:05:41,230 TO BE USED AS A GUIDE. 8117 06:05:41,230 --> 06:05:44,700 AND SHOULD BE PERFORMED BY AN 8118 06:05:44,700 --> 06:05:47,736 ASSESSMENT TEAM WHO HAS 8119 06:05:47,736 --> 06:05:52,341 KNOWLEDGE IN SICKLE CELL AND 8120 06:05:52,341 --> 06:06:01,684 EXPERTISE IN INTERVIEWING. 8121 06:06:01,684 --> 06:06:04,053 AND INFORM DECISION AND HAVE 8122 06:06:04,053 --> 06:06:06,822 OPEN DIALOGUE BETWEEN THE 8123 06:06:06,822 --> 06:06:09,124 CLINICIAN AND PATIENT REGARDING 8124 06:06:09,124 --> 06:06:13,562 READINESS FOR GENE THERAPY AND 8125 06:06:13,562 --> 06:06:16,131 WHILE THE P.I. MAY BE THOSE WHO 8126 06:06:16,131 --> 06:06:20,669 LEAD THE EFFORTS TO EVALUATE FOR 8127 06:06:20,669 --> 06:06:23,405 READINESS, IT'S IMPORTANT THE 8128 06:06:23,405 --> 06:06:24,206 ATTENTION RESPONSIBILITY OF THE 8129 06:06:24,206 --> 06:06:25,274 TREATMENT TEAM AND THE 8130 06:06:25,274 --> 06:06:30,145 ASSESSMENT IS INTENDED TO 8131 06:06:30,145 --> 06:06:31,180 ENHANCE OUTCOMES AND OPTIMIZE 8132 06:06:31,180 --> 06:06:41,357 TREATMENT. 8133 06:06:44,260 --> 06:06:46,562 WE FOCUSSED ON GENE THERAPY AND 8134 06:06:46,562 --> 06:06:48,931 DR. VALRIE WILL JOIN US AGAIN 8135 06:06:48,931 --> 06:06:52,701 AND TALK ABOUT NEXT STEPS FOR 8136 06:06:52,701 --> 06:07:00,376 OUR WORKING GROUP. 8137 06:07:00,376 --> 06:07:02,978 SO AS WE MOVE FORWARD AND THINK 8138 06:07:02,978 --> 06:07:07,349 ABOUT WHAT ARE SOME IMPORTANT 8139 06:07:07,349 --> 06:07:10,920 NEXT STEPS WE WANT TO MAKE SURE 8140 06:07:10,920 --> 06:07:12,288 THE THERAPY PSYCHOSOCIAL 8141 06:07:12,288 --> 06:07:18,928 ASSESSMENT GUIDELINES ARE FULLY 8142 06:07:18,928 --> 06:07:22,097 DISSEMINATED AND IMPLEMENTS IN 8143 06:07:22,097 --> 06:07:24,300 RELATION TO GENE THERAPY AND 8144 06:07:24,300 --> 06:07:24,867 THOSE CURRENTLY DOING GENE 8145 06:07:24,867 --> 06:07:35,010 THERAPY. 8146 06:07:37,513 --> 06:07:39,248 AND GUIDELINES FOR PSYCHOSOCIAL 8147 06:07:39,248 --> 06:07:48,924 SUPPORTS. 8148 06:07:48,924 --> 06:07:51,293 DIGGING INTO ACTIVITIES WITH 8149 06:07:51,293 --> 06:07:52,761 PREEXISTING THERAPY GUIDELINES, 8150 06:07:52,761 --> 06:07:57,866 ONE IS WE'RE PLANNING A SURVEY 8151 06:07:57,866 --> 06:08:08,577 OF CENTERS WHAT ARE TE STAFF AND 8152 06:08:27,363 --> 06:08:28,430 RESOURCES THAT NEED TO BE IN 8153 06:08:28,430 --> 06:08:30,566 PLACE TO MAKE THE SUPPORT HAPPEN 8154 06:08:30,566 --> 06:08:32,134 AND WE'RE DEFINITELY LOOKING TO 8155 06:08:32,134 --> 06:08:35,170 DEVELOP PARTNERSHIPS WITH SICKLE 8156 06:08:35,170 --> 06:08:35,904 CELL RESEARCHERS AND CLINICIANS 8157 06:08:35,904 --> 06:08:40,142 AND NETWORKS TO CONTINUE TO 8158 06:08:40,142 --> 06:08:40,743 FACILITATE THE IMPLEMENTATION 8159 06:08:40,743 --> 06:08:50,953 ACTIVITIES. 8160 06:08:59,094 --> 06:09:02,064 AND WE HAVE LITERATURE REVIEW OF 8161 06:09:02,064 --> 06:09:03,832 PSYCHOSOCIAL CONCERNS POST GENE 8162 06:09:03,832 --> 06:09:06,368 THERAPY FOR OTHER CHRONICALLY 8163 06:09:06,368 --> 06:09:07,269 ILL POPULATIONS AS THERE'S A LOT 8164 06:09:07,269 --> 06:09:08,370 OF EXPERIENCE. 8165 06:09:08,370 --> 06:09:10,372 AND WE ALSO PLAN TO CONDUCT 8166 06:09:10,372 --> 06:09:12,474 FOCUS GROUPS OF PROVIDERS, 8167 06:09:12,474 --> 06:09:13,876 PEOPLE WITH SICKLE CELL DISEASE 8168 06:09:13,876 --> 06:09:15,344 WHO HAVE UNDER GONE GENE THERAPY 8169 06:09:15,344 --> 06:09:16,645 AND THEIR CAREGIVERS. 8170 06:09:16,645 --> 06:09:19,581 WE ALSO PLAN TO DEVELOP OUR 8171 06:09:19,581 --> 06:09:22,384 ITERATIVE PROCESS TO DEVELOP THE 8172 06:09:22,384 --> 06:09:24,486 LINES WITH A FOCUS ON PROVIDING 8173 06:09:24,486 --> 06:09:25,721 RECOMMENDATIONS FOR ONE TO TWO 8174 06:09:25,721 --> 06:09:27,890 YEARS AND TWO TO FIVE YEARS OUT 8175 06:09:27,890 --> 06:09:30,392 AND FIVE TO 15 YEARS POST GENE 8176 06:09:30,392 --> 06:09:35,197 THERAPY GIVEN THE MANDATE OF 15 8177 06:09:35,197 --> 06:09:36,665 YEARS OF POST GENE THERAPY 8178 06:09:36,665 --> 06:09:38,167 FOLLOW UP. 8179 06:09:38,167 --> 06:09:40,235 I DIDN'T MEAN TO SPEED THROUGH 8180 06:09:40,235 --> 06:09:40,469 SLIDES. 8181 06:09:40,469 --> 06:09:41,837 GO BACK TWO SLIDES, PLEASE. 8182 06:09:41,837 --> 06:09:43,405 OUR PLAN IS TO WORK IN 8183 06:09:43,405 --> 06:09:45,374 CONJUNCTION TO MAKE THIS HAPPEN 8184 06:09:45,374 --> 06:09:47,009 WITH THE CURES ACT COMMUNITY 8185 06:09:47,009 --> 06:09:49,011 INPUT PANEL AS WELL AS OTHER 8186 06:09:49,011 --> 06:09:54,216 PARTNERS WHO MAY BE AVAILABLE. 8187 06:09:54,216 --> 06:09:58,921 I ALSO WANT TO MENTION ME AND 8188 06:09:58,921 --> 06:09:59,988 JERLYM REPRESENT A LARGER GROUP 8189 06:09:59,988 --> 06:10:01,490 AND THANK YOU TO OUR PAST 8190 06:10:01,490 --> 06:10:04,560 MEMBERS WHO WERE A PART OF PHASE 8191 06:10:04,560 --> 06:10:08,063 1 IN DEVELOPING OUR THERAPY 8192 06:10:08,063 --> 06:10:12,668 GUIDELINES AND CURRENT AND NEW 8193 06:10:12,668 --> 06:10:16,672 MEMBERS WHO JOINED TO CONTINUE 8194 06:10:16,672 --> 06:10:19,007 TO EXPAND THE EXPERTISE ON THE 8195 06:10:19,007 --> 06:10:19,508 TEAM. 8196 06:10:19,508 --> 06:10:22,745 WE'RE A TEAM OF PSYCHOLOGISTS 8197 06:10:22,745 --> 06:10:24,279 AND MENTAL HEALTH PROFESSIONALS, 8198 06:10:24,279 --> 06:10:26,448 SOCIAL WORKERS, PATIENT 8199 06:10:26,448 --> 06:10:28,450 NAVIGATORS AND OTHERS WITH THOSE 8200 06:10:28,450 --> 06:10:29,151 EXPERIENCES AS WELL AS 8201 06:10:29,151 --> 06:10:30,652 IMPORTANTLY PEOPLE WHO ARE 8202 06:10:30,652 --> 06:10:32,521 LOVING WITH SICKLE CELL DISEASE 8203 06:10:32,521 --> 06:10:35,491 SOME WHO HAVE BEEN THROUGH 8204 06:10:35,491 --> 06:10:36,125 TRANSFORMATIVE THERAPY AS WELL 8205 06:10:36,125 --> 06:10:38,160 AS A CAREGIVER OF A YOUNG WOMAN 8206 06:10:38,160 --> 06:10:40,662 WHO EXPERIENCED A TRANSFORMATIVE 8207 06:10:40,662 --> 06:10:41,630 THERAPY. 8208 06:10:41,630 --> 06:10:43,665 A SPECIAL THANK YOU TO OUR PHASE 8209 06:10:43,665 --> 06:10:47,136 1 LEADER, DR. HARDY AT 8210 06:10:47,136 --> 06:10:48,403 CHILDREN'S NATIONAL HOSPITAL AND 8211 06:10:48,403 --> 06:10:54,943 FOR ALL THE SUPPORT WE'VE 8212 06:10:54,943 --> 06:11:05,454 RECEIVED FROM NHLBI AND STAFF. 8213 06:11:06,989 --> 06:11:10,959 THIS IS WHERE I'LL END AND 8214 06:11:10,959 --> 06:11:12,227 ANSWER QUESTIONS AND I KNOW 8215 06:11:12,227 --> 06:11:13,595 WE'LL GO INTO A PANEL WHERE 8216 06:11:13,595 --> 06:11:15,998 WE'LL ALSO BE ABLE TO ANSWER 8217 06:11:15,998 --> 06:11:16,398 QUESTIONS. 8218 06:11:16,398 --> 06:11:17,866 >> ARE THERE ANY QUESTIONS AT 8219 06:11:17,866 --> 06:11:18,500 THIS TIME BEFORE WE HEAD TO OUR 8220 06:11:18,500 --> 06:11:28,811 PANEL DISCUSSION? 8221 06:11:30,479 --> 06:11:30,813 OKAY. 8222 06:11:30,813 --> 06:11:33,882 I'M HEATHER AVANT THE CHAIR OF 8223 06:11:33,882 --> 06:11:34,616 THE CURE SICKLE CELL INITIATIVE 8224 06:11:34,616 --> 06:11:37,452 AND MY GOAL IS TO REPRESENT THE 8225 06:11:37,452 --> 06:11:37,786 COMMUNITY. 8226 06:11:37,786 --> 06:11:40,355 THE GOAL IS TO BE THE VOICE. 8227 06:11:40,355 --> 06:11:50,899 WE ARE A PANEL OF PATIENTS AND 8228 06:11:52,000 --> 06:11:53,168 CAREGIVERS AND AROUND EVERYTHING 8229 06:11:53,168 --> 06:11:54,403 AND ANYTHING IN DEVELOP. 8230 06:11:54,403 --> 06:11:56,171 IF YOU CAN THINK IT, WE'VE 8231 06:11:56,171 --> 06:11:56,672 DISCUSSED IT. 8232 06:11:56,672 --> 06:11:58,340 THE GOAL OF THIS PANEL IS TO DIG 8233 06:11:58,340 --> 06:12:00,943 DEEP INTO WHAT THE PATIENTS AND 8234 06:12:00,943 --> 06:12:02,444 CAREGIVERS IN THE COMMUNITY ARE 8235 06:12:02,444 --> 06:12:04,847 CURRENTLY THINKING ABOUT WHEN IT 8236 06:12:04,847 --> 06:12:11,987 COMES TO TRANSFORMATIONAL 8237 06:12:11,987 --> 06:12:17,593 THERAPIES AND MENTAL HEALTH AND 8238 06:12:17,593 --> 06:12:17,860 APHERESIS. 8239 06:12:17,860 --> 06:12:18,927 I'LL LET ADRIENNE ASK THE FIRST 8240 06:12:18,927 --> 06:12:29,104 QUESTION. 8241 06:12:30,172 --> 06:12:35,644 I'M SO EXCITED BECAUSE WE HAVE 8242 06:12:35,644 --> 06:12:39,481 THE TWO OF YOU HERE. 8243 06:12:39,481 --> 06:12:41,550 IT'S SOMETHING WE AS PARENTS AND 8244 06:12:41,550 --> 06:12:42,918 WARRIORS HAVE DEALT WITH FOR A 8245 06:12:42,918 --> 06:12:44,353 LONG TIME. 8246 06:12:44,353 --> 06:12:50,058 YOU'RE THERE NOW, WE'RE ALL 8247 06:12:50,058 --> 06:13:00,402 TOGETHER AND THERE'S QUESTIONS 8248 06:13:00,402 --> 06:13:04,006 ABOUT WARRIORS AND FAMILY WHERE 8249 06:13:04,006 --> 06:13:06,041 PEOPLE ARE GETTING BLOOD 8250 06:13:06,041 --> 06:13:06,508 THERAPIES. 8251 06:13:06,508 --> 06:13:08,644 THEY MAY BE GETTING BOLD 8252 06:13:08,644 --> 06:13:08,977 TRANSFUSIONS. 8253 06:13:08,977 --> 06:13:11,346 THEY MAY BE GETTING RED BLOOD 8254 06:13:11,346 --> 06:13:16,218 EXCHANGES AND THERE'S A LOT OF 8255 06:13:16,218 --> 06:13:17,552 CONCERN THAT BEING ON THOSE 8256 06:13:17,552 --> 06:13:23,558 THERAPIES WILL PREVENT THEM FROM 8257 06:13:23,558 --> 06:13:24,126 HAVING ACCESS. 8258 06:13:24,126 --> 06:13:29,998 LET'S TALK ABOUT THAT. 8259 06:13:29,998 --> 06:13:32,401 >> IT'S A VERY GOOD POINT 8260 06:13:32,401 --> 06:13:34,937 BECAUSE MANY PATIENTS ON CHRONIC 8261 06:13:34,937 --> 06:13:36,438 EXCHANGE PROGRAMS AND CHRONIC 8262 06:13:36,438 --> 06:13:37,039 TRANSFUSION PROGRAMS SUDDENLY 8263 06:13:37,039 --> 06:13:44,646 FEEL WELL. 8264 06:13:44,646 --> 06:13:46,481 IT'S VERY HARD FOR THEM TO THINK 8265 06:13:46,481 --> 06:13:48,483 OF OTHER THERAPIES AND 8266 06:13:48,483 --> 06:13:49,084 TRANSFORMATIVE THERAPIES THAT 8267 06:13:49,084 --> 06:13:52,621 MATTER WHEN THEY'RE IN A GOOD 8268 06:13:52,621 --> 06:13:55,991 PLACE IN THEIR LIFE. 8269 06:13:55,991 --> 06:13:59,127 THIS WAS BROUGHT UP IN THE 8270 06:13:59,127 --> 06:14:00,629 PREVIOUS PANEL WHEN THEIR 8271 06:14:00,629 --> 06:14:03,632 PATIENTS THAT HAVE BEEN ILL AND 8272 06:14:03,632 --> 06:14:05,233 ALL OF A SUDDEN TRANSFUSION 8273 06:14:05,233 --> 06:14:08,570 CHANGED THAT TRAJECTORY. 8274 06:14:08,570 --> 06:14:09,805 NOW THEY'RE FEELING LIKE THEY 8275 06:14:09,805 --> 06:14:14,343 MAY NOT BE SEEKING OUT MORE 8276 06:14:14,343 --> 06:14:16,645 ADVANCED THERAPIES AND MAY BE 8277 06:14:16,645 --> 06:14:21,917 HAPPY WHERE THEY ARE AND THE 8278 06:14:21,917 --> 06:14:25,187 QUESTION WE GET SOMETIMES IS IS 8279 06:14:25,187 --> 06:14:26,054 IT TIME TO THINK ABOUT SOMETHING 8280 06:14:26,054 --> 06:14:29,391 ELSE AN IT'S HARD TO MAKE THE 8281 06:14:29,391 --> 06:14:29,791 LEAP. 8282 06:14:29,791 --> 06:14:31,827 IT TAKES A LONG CONVERSATION BUT 8283 06:14:31,827 --> 06:14:33,662 FROM THE TRANSFUSION SIDE IT'S 8284 06:14:33,662 --> 06:14:39,668 JUST IMPORTANT TO KEEP THAT 8285 06:14:39,668 --> 06:14:42,938 DIALOGUE GOING AND KEEP THE 8286 06:14:42,938 --> 06:14:46,108 HEMATOLOGIST INVOLVED AND TRY TO 8287 06:14:46,108 --> 06:14:51,947 UNDERSTAND WHY THE PATIENT IS 8288 06:14:51,947 --> 06:14:59,821 EVEN ASKING THE QUESTION. 8289 06:14:59,821 --> 06:15:01,790 >> DR. MANIS THE QUESTION WE GET 8290 06:15:01,790 --> 06:15:03,325 FROM THE COMMUNITY OFTEN OR I 8291 06:15:03,325 --> 06:15:06,862 HEAR OFTEN IS WHAT IS THE TIME 8292 06:15:06,862 --> 06:15:09,131 LINE FOR PREPARING FOR IN 8293 06:15:09,131 --> 06:15:11,299 HOSPITAL AND PRIOR TO RECEIVING 8294 06:15:11,299 --> 06:15:12,067 THE PRODUCT. 8295 06:15:12,067 --> 06:15:13,902 PATIENTS ARE ALWAYS ASKING ABOUT 8296 06:15:13,902 --> 06:15:14,269 TIME. 8297 06:15:14,269 --> 06:15:16,104 HOW MUCH TIME DO I OWE OR WILL I 8298 06:15:16,104 --> 06:15:17,406 HAVE TO DO? 8299 06:15:17,406 --> 06:15:20,275 I KNOW THERE'S NEVER AN EXACT 8300 06:15:20,275 --> 06:15:21,376 ANSWER BUT WHAT WOULD BE YOUR 8301 06:15:21,376 --> 06:15:28,383 ANSWER TO THE COMMUNITY? 8302 06:15:28,383 --> 06:15:30,052 >> THIS IS A TOUGH QUESTION IN 8303 06:15:30,052 --> 06:15:32,621 THE FACE OF AN EVOLVING FIELD 8304 06:15:32,621 --> 06:15:38,226 BUT I WOULD SAY BACK OF THE 8305 06:15:38,226 --> 06:15:39,694 ENVELOPE FIRST ANSWER WOULD BE 8306 06:15:39,694 --> 06:15:44,733 TO THINK ABOUT THE EXPECTATION 8307 06:15:44,733 --> 06:15:48,070 OF THE PATIENT AND WHAT I'M 8308 06:15:48,070 --> 06:15:54,443 GETTING TO IS WHY IS TIME 8309 06:15:54,443 --> 06:15:54,709 IMPORTANT? 8310 06:15:54,709 --> 06:15:56,478 IS IT BECAUSE TO PLAN TIME AWAY 8311 06:15:56,478 --> 06:15:59,181 FROM WORK OR BECAUSE OF FAMILY 8312 06:15:59,181 --> 06:16:00,348 RESPONSIBILITIES OR TO FEEL 8313 06:16:00,348 --> 06:16:00,715 BETTER? 8314 06:16:00,715 --> 06:16:01,783 THOSE ARE ALL VERY DIFFERENT 8315 06:16:01,783 --> 06:16:04,553 ANSWERS FOR TIME. 8316 06:16:04,553 --> 06:16:06,188 BECAUSE IF YOU TELL SOMEBODY WHO 8317 06:16:06,188 --> 06:16:08,156 IS IN PAIN ONE YEAR BEFORE YOU 8318 06:16:08,156 --> 06:16:10,559 GET A TRANSPLANT, THAT MAY BE 8319 06:16:10,559 --> 06:16:12,561 ABOUT WHAT THEY'VE PUT A HOOK ON 8320 06:16:12,561 --> 06:16:15,764 TO FEEL BETTER BUT WE ALL KNOW 8321 06:16:15,764 --> 06:16:16,398 IT WILL TAKE SIX MONTHS AFTER 8322 06:16:16,398 --> 06:16:21,336 THAT OR NINE MONTHS AFTER THAT 8323 06:16:21,336 --> 06:16:24,339 BEFORE THEY REALLY CHANGE AND 8324 06:16:24,339 --> 06:16:25,440 FEEL BETTER. 8325 06:16:25,440 --> 06:16:27,609 TECHNICALLY I WOULD SAY NINE 8326 06:16:27,609 --> 06:16:30,979 MONTHS IS A GOOD ESTIMATION OF 8327 06:16:30,979 --> 06:16:37,886 ENTRY TO THE STUDY TO BEING 8328 06:16:37,886 --> 06:16:38,687 TRANSPLANTED AND DURING THAT 8329 06:16:38,687 --> 06:16:39,921 TIME THE MAJORITY OF THE TIME 8330 06:16:39,921 --> 06:16:41,590 YOU'RE GETTING TRANSFUSIONS OR 8331 06:16:41,590 --> 06:16:52,033 SOME TRANSFUSION THERAPY. 8332 06:17:11,553 --> 06:17:15,724 >> WE HEAR THIS ALL THE TIME. 8333 06:17:15,724 --> 06:17:23,165 I'M A WARRIOR AND WITH THE 8334 06:17:23,165 --> 06:17:27,869 TREATMENT AND I'M NO LONGER 8335 06:17:27,869 --> 06:17:33,208 HAVING THOSE DAILY CHALLENGES, 8336 06:17:33,208 --> 06:17:43,652 WHAT DO YOU FORESEE BEING 8337 06:17:50,392 --> 06:17:52,627 GUARDRAILS AND THOSE REAPING 8338 06:17:52,627 --> 06:18:01,236 BENEFITS AND THOSE HO DON'T. 8339 06:18:01,236 --> 06:18:04,606 WHERE DO YOU SEE GUARDRAILS TO 8340 06:18:04,606 --> 06:18:14,749 HELP US? 8341 06:18:17,052 --> 06:18:19,654 >> THERE'S PSYCHOSOCIAL SUPPORT 8342 06:18:19,654 --> 06:18:21,122 FROM THE GET GO. 8343 06:18:21,122 --> 06:18:23,725 IF EVER CENTER COULD HAVE A 8344 06:18:23,725 --> 06:18:25,026 PSYCHOLOGIST OR SOCIAL WORKER 8345 06:18:25,026 --> 06:18:26,528 ORE ANOTHER MENTAL HEALTH 8346 06:18:26,528 --> 06:18:31,800 CLINICIAN THAT IS THERE FROM THE 8347 06:18:31,800 --> 06:18:33,668 BEGINNING AND THROUGHOUT THE 8348 06:18:33,668 --> 06:18:34,069 PROCESS. 8349 06:18:34,069 --> 06:18:36,938 I ALSO THINK IT'S IMPORTANT WE 8350 06:18:36,938 --> 06:18:39,474 AS CENTERS REALLY LOOK OUTSIDE 8351 06:18:39,474 --> 06:18:41,843 IN THE COMMUNITY AT OTHER MENTAL 8352 06:18:41,843 --> 06:18:44,279 HEALTH SUPPORTS BECAUSE THEY MAY 8353 06:18:44,279 --> 06:18:46,581 NOT ALWAYS BE ABLE TO COME BACK 8354 06:18:46,581 --> 06:18:48,617 TO US AT THE INSTITUTION SO WE 8355 06:18:48,617 --> 06:18:51,853 NEED TO GIVE THEM THE RESOURCES 8356 06:18:51,853 --> 06:18:52,587 IN THE COMMUNITY. 8357 06:18:52,587 --> 06:18:55,824 FIND THE RESOURCES AND HAVE 8358 06:18:55,824 --> 06:18:57,125 THOSE INDIVIDUALS THAT CAN 8359 06:18:57,125 --> 06:19:05,667 PROVIDE THAT ADDITIONAL SUPPORT. 8360 06:19:05,667 --> 06:19:07,235 AND IT'S IMPORTANT TO TALK ABOUT 8361 06:19:07,235 --> 06:19:12,274 EXPECTATIONS AT THE BEGINNING. 8362 06:19:12,274 --> 06:19:14,175 WHAT DOES SUCCESS LOOK LIKE AND 8363 06:19:14,175 --> 06:19:18,813 WHAT DOES SUCCESS NOT LOOK LIKE. 8364 06:19:18,813 --> 06:19:20,215 IF IT DOESN'T WORK WHAT WOULD 8365 06:19:20,215 --> 06:19:21,449 THAT LOOK LIKE AND WHAT DOES IT 8366 06:19:21,449 --> 06:19:23,051 LOOK LIKE SOMEWHERE IN BETWEEN 8367 06:19:23,051 --> 06:19:31,326 BECAUSE YOU DON'T KNOW. 8368 06:19:31,326 --> 06:19:34,229 >> SO WHO IS RESPONSIBLE FOR THE 8369 06:19:34,229 --> 06:19:36,064 PATIENT'S MENTAL HEALTH LONG 8370 06:19:36,064 --> 06:19:36,264 TERM? 8371 06:19:36,264 --> 06:19:38,667 WE TALKED ABOUT DURING THE 8372 06:19:38,667 --> 06:19:41,102 PROCESS OR RIGHT AFTER BUT THE 8373 06:19:41,102 --> 06:19:44,172 MENTAL HEALTH IMPLICATIONS. 8374 06:19:44,172 --> 06:19:46,274 THE PERSON GOES FROM A WARRIOR 8375 06:19:46,274 --> 06:19:48,176 TO WARRIOR-SURVIVOR. 8376 06:19:48,176 --> 06:19:49,611 WHAT'S THAT MEAN AND WHO IS 8377 06:19:49,611 --> 06:19:51,379 RESPONSIBLE FOR TAKING CARE OF 8378 06:19:51,379 --> 06:19:53,581 THE PATIENT LONG TERM? 8379 06:19:53,581 --> 06:19:55,483 A LOT OF TIMES PATIENTS ARE 8380 06:19:55,483 --> 06:20:00,922 OFTEN DISENFRANCHISED AFTER 8381 06:20:00,922 --> 06:20:11,333 GOING THROUGH A THERAPY. 8382 06:20:20,875 --> 06:20:23,812 >> I'M A PSYCHOLOGIST SO I'M 8383 06:20:23,812 --> 06:20:30,618 ALWAYS PROTHE THERAPY AND 8384 06:20:30,618 --> 06:20:30,885 PROACTIVE. 8385 06:20:30,885 --> 06:20:33,154 LET'S USE THERAPY TO THINK AHEAD 8386 06:20:33,154 --> 06:20:35,190 OF THE CHALLENGES THAT MIGHT 8387 06:20:35,190 --> 06:20:36,725 COME IN THE FUTURE. 8388 06:20:36,725 --> 06:20:39,260 I THINK WE NEED TO -- AT OUR 8389 06:20:39,260 --> 06:20:40,595 INSTITUTIONS WE NEED TO DO A 8390 06:20:40,595 --> 06:20:42,297 BETTER JOB OF PARTNERING WITH 8391 06:20:42,297 --> 06:20:43,665 THE COMMUNITY TO FIND OUT WHO 8392 06:20:43,665 --> 06:20:46,534 ARE THE MENTAL HEALTH PROVIDERS 8393 06:20:46,534 --> 06:20:48,870 OUT THERE AND PROVIDING SOME 8394 06:20:48,870 --> 06:20:51,573 EDUCATION TO MENTAL HEALTH 8395 06:20:51,573 --> 06:20:52,574 PROVIDERS ABOUT SICKLE CELL 8396 06:20:52,574 --> 06:20:54,609 DISEASE AND GOING THROUGH 8397 06:20:54,609 --> 06:20:56,077 TRANSFORMATIVE THERAPY AND WHAT 8398 06:20:56,077 --> 06:21:01,750 THAT LOOKS LIKE AFTER THERAPY IS 8399 06:21:01,750 --> 06:21:02,016 FINISHED. 8400 06:21:02,016 --> 06:21:04,586 HOW TO BEST SUPPORT THEM IN 8401 06:21:04,586 --> 06:21:07,355 WHATEVER OUTCOME IT IS. 8402 06:21:07,355 --> 06:21:08,056 >> I'M UNSURE PEOPLE CAN HEAR ME 8403 06:21:08,056 --> 06:21:18,566 S&P I LIKE THE IDEA OF SHARED 8404 06:21:27,242 --> 06:21:28,610 RESPONSIBILITY AND I ECHO 8405 06:21:28,610 --> 06:21:30,211 EVERYTHING DR. PORTER HAS SAID 8406 06:21:30,211 --> 06:21:32,380 IN RELATION TO PROVIDING SUPPORT 8407 06:21:32,380 --> 06:21:34,315 WITHIN THE HEALTH CARE TEAM I 8408 06:21:34,315 --> 06:21:36,584 THINK MENTAL HEALTH AND 8409 06:21:36,584 --> 06:21:39,020 PSYCHOSOCIAL SUPPORT BOTH THE 8410 06:21:39,020 --> 06:21:40,388 ASSESSMENT AND THE CONNECTING 8411 06:21:40,388 --> 06:21:42,323 WITH RESOURCES NEEDS TO COME 8412 06:21:42,323 --> 06:21:45,360 FROM THE ENTIRE TEAM AS 8413 06:21:45,360 --> 06:21:47,295 SUPPORTED BY THE POINT PERSON. 8414 06:21:47,295 --> 06:21:49,030 BUT THAT WE HAVE TO REALLY ACT 8415 06:21:49,030 --> 06:21:51,966 AS A TEAM AROUND THIS THE SAME 8416 06:21:51,966 --> 06:21:54,836 WE WE ACT AS A TEAM AROUND OTHER 8417 06:21:54,836 --> 06:21:55,770 ASPECTS OF CARE. 8418 06:21:55,770 --> 06:22:00,208 I ALSO WANT TO SAY THAT THOUGH 8419 06:22:00,208 --> 06:22:06,581 WE SHOULD HAVE A GOOD FOCUS ON 8420 06:22:06,581 --> 06:22:08,316 THE PERSON LIVING WITH SICKLE 8421 06:22:08,316 --> 06:22:09,284 CELL SOMETIMES PROVIDING THE 8422 06:22:09,284 --> 06:22:10,552 SUPPORT TO THEIR SUPPORT SYSTEM 8423 06:22:10,552 --> 06:22:12,053 IS JUST AS IMPORTANT WHETHER 8424 06:22:12,053 --> 06:22:15,623 IT'S A PEDIATRIC PATIENT OR 8425 06:22:15,623 --> 06:22:17,125 CAREGIVER OR PATIENT OR THE 8426 06:22:17,125 --> 06:22:19,727 OTHER CAREGIVERS FOR ADULT 8427 06:22:19,727 --> 06:22:20,862 PATIENTS, WE ALSO SHOULD 8428 06:22:20,862 --> 06:22:25,934 SOMETIMES HAVE TO THINK OUTSIDE 8429 06:22:25,934 --> 06:22:31,806 THE BOX AND THE PATIENTS ARE 8430 06:22:31,806 --> 06:22:33,641 EMBEDDED WITHIN COMMUNITIES AND 8431 06:22:33,641 --> 06:22:36,144 IT'S IMPORTANT WHEN THERE'S GOOD 8432 06:22:36,144 --> 06:22:39,547 AND SOMETIMES POORER OUTCOMES. 8433 06:22:39,547 --> 06:22:42,083 I THINK THIS HAS ALSO BEEN 8434 06:22:42,083 --> 06:22:45,353 ECHOED BY A PARENT WHO HAS LOST 8435 06:22:45,353 --> 06:22:48,556 A YOUNG PERSON TO COMPLICATIONS 8436 06:22:48,556 --> 06:22:50,725 OF SICKLE CELL DISEASE MAKING 8437 06:22:50,725 --> 06:22:51,793 SURE THAT JUST BECAUSE THE 8438 06:22:51,793 --> 06:22:53,428 IDENTIFIED PATIENT IS NO LONGER 8439 06:22:53,428 --> 06:22:56,197 THERE, DOESN'T MEAN THE PEOPLE 8440 06:22:56,197 --> 06:22:57,799 WHO ARE SUPPORTING THEM DON'T 8441 06:22:57,799 --> 06:22:59,400 NEED THE SAME CARE AND SUPPORT 8442 06:22:59,400 --> 06:22:59,968 AS THEY TRANSITION TO A NEW 8443 06:22:59,968 --> 06:23:10,111 REALITY. 8444 06:23:24,626 --> 06:23:26,361 >> SO ABOUT WHAT DO WE HAVE IN 8445 06:23:26,361 --> 06:23:26,728 PLACE? 8446 06:23:26,728 --> 06:23:28,563 I HEAR YOU TALK ABOUT REGISTRIES 8447 06:23:28,563 --> 06:23:39,040 AND NARRATIVES AND ALL THAT. 8448 06:23:40,208 --> 06:23:41,175 ARE WE PUTTING SOMETHING IN 8449 06:23:41,175 --> 06:23:51,586 PLACE FOR US TO DO THAT? 8450 06:24:00,295 --> 06:24:03,331 >> I THINK PEOPLE NEED TO GET 8451 06:24:03,331 --> 06:24:04,799 THE WORD OUT. 8452 06:24:04,799 --> 06:24:10,104 WARRIORS AND PEOPLE WHO SUPPORT 8453 06:24:10,104 --> 06:24:17,211 THEM PROVIDERS AND GET IT OUT IN 8454 06:24:17,211 --> 06:24:18,613 A SOCIAL MEDIA PODCAST. 8455 06:24:18,613 --> 06:24:20,582 THE WARRIOR AN SUPPORTER 8456 06:24:20,582 --> 06:24:25,720 EXPERIENCE IS INVALUABLE. 8457 06:24:25,720 --> 06:24:28,256 I CAN TALK ABOUT SICKLE CELL 8458 06:24:28,256 --> 06:24:29,824 EXPERIENCE AS A PROVIDER BUT AT 8459 06:24:29,824 --> 06:24:34,529 THE END OF THE DAY YOU ALL ARE 8460 06:24:34,529 --> 06:24:35,363 THE EXPERTS. 8461 06:24:35,363 --> 06:24:37,832 WE AS PROVIDERS AT INSTITUTIONS, 8462 06:24:37,832 --> 06:24:39,467 WE CAN DO THINGS TO SUPPORT YOU 8463 06:24:39,467 --> 06:24:43,171 ALL TO GET THE WORD OUT. 8464 06:24:43,171 --> 06:24:45,740 SO THAT PEOPLE KNOW WHETHER THE 8465 06:24:45,740 --> 06:24:48,576 EXPERIENCE IS LIKE AND YOU QUAN 8466 06:24:48,576 --> 06:24:50,144 GIVE THAT KNOWLEDGE AS AN EXPERT 8467 06:24:50,144 --> 06:24:55,216 I THINK WE CAN ALL DO A BETTER 8468 06:24:55,216 --> 06:24:56,250 JOB AT THAT. 8469 06:24:56,250 --> 06:24:58,853 ALSO I SEE DR. SMITH. 8470 06:24:58,853 --> 06:25:00,121 >> YOU STOLE MY THUNDER. 8471 06:25:00,121 --> 06:25:03,791 I WAS GOING TO TALK ABOUT 8472 06:25:03,791 --> 06:25:05,226 PHONING AN A FRIEND, SPORT 8473 06:25:05,226 --> 06:25:15,670 GROUPS AND OTHER MEANS OF MAKING 8474 06:25:15,670 --> 06:25:17,605 IT REAL TO SOMEBODY CONSIDERING 8475 06:25:17,605 --> 06:25:17,839 THERAPY. 8476 06:25:17,839 --> 06:25:21,709 SOMEBODY WHO IS GOING THROUGH 8477 06:25:21,709 --> 06:25:22,276 AND SUCCEEDING. 8478 06:25:22,276 --> 06:25:25,413 SOMEBODY GOING THROUGH AND 8479 06:25:25,413 --> 06:25:26,514 FAILING. 8480 06:25:26,514 --> 06:25:28,049 I THINK PHONE A FRIEND AND 8481 06:25:28,049 --> 06:25:29,817 SUPPORT GROUPS, I SEE US AS 8482 06:25:29,817 --> 06:25:33,888 LACKING IN THAT. 8483 06:25:33,888 --> 06:25:36,190 WHERE HE MAY HAVE MORE 8484 06:25:36,190 --> 06:25:38,426 PSYCHOLOGISTS AND THERAPISTS AND 8485 06:25:38,426 --> 06:25:44,565 TEAM MEMBERS SURROUNDING THE 8486 06:25:44,565 --> 06:25:47,001 PATIENT THAN SOMEBODY GOING 8487 06:25:47,001 --> 06:25:47,835 THROUGH THE THERAPY. 8488 06:25:47,835 --> 06:25:50,672 IT WAS SORELY LACKING IN MY 8489 06:25:50,672 --> 06:25:52,573 CENTER AND CECELIA AND I HAVE A 8490 06:25:52,573 --> 06:25:54,909 PATIENT WE SHARE THAT WOULD HAVE 8491 06:25:54,909 --> 06:25:56,544 BENEFITTED IF THE PERSON HAD 8492 06:25:56,544 --> 06:25:58,246 SOMEONE LIKE THAT TO TALK TO, DO 8493 06:25:58,246 --> 06:25:58,880 YOU AGREE? 8494 06:25:58,880 --> 06:26:09,123 >> YOU STOLE MY THUNDER. 8495 06:26:09,123 --> 06:26:12,126 WHAT ARE WE PUTTING IN PLACE TO 8496 06:26:12,126 --> 06:26:14,028 ALLOW FOR PATIENTS TO SHARE 8497 06:26:14,028 --> 06:26:15,363 THEIR STORIES? 8498 06:26:15,363 --> 06:26:18,232 ARE WE LAYERING IN OTHER 8499 06:26:18,232 --> 06:26:19,801 PATIENTS BECAUSE WE HAVE MORE 8500 06:26:19,801 --> 06:26:22,403 AND MORE ALL THE TIME. 8501 06:26:22,403 --> 06:26:25,206 AND WE'RE HEARING ABOUT MORE 8502 06:26:25,206 --> 06:26:27,375 SUCCESSFUL OR UNSUCCESSFUL 8503 06:26:27,375 --> 06:26:29,477 TRANSPLANTS FOR THAT MATTER AND 8504 06:26:29,477 --> 06:26:34,382 WHAT ARE WE GOING TO LAYER THEIR 8505 06:26:34,382 --> 06:26:36,417 STORIES AND IT'S A QUESTION THAT 8506 06:26:36,417 --> 06:26:46,294 COMES UP OFTEN. 8507 06:26:46,294 --> 06:26:47,862 >> FROM MY PERSPECTIVE PARTLY 8508 06:26:47,862 --> 06:26:51,132 WHAT WE THINK NEEDS IT HAPPEN IS 8509 06:26:51,132 --> 06:26:54,702 RIGHT NOW THE PRIMARY STORIES 8510 06:26:54,702 --> 06:26:56,137 GETTING OUT THERE HITTING THE 8511 06:26:56,137 --> 06:27:01,342 COMMUNITY ARE COMING THROUGH 8512 06:27:01,342 --> 06:27:03,244 STANDARDIZED MEDIA AND THEY'RE 8513 06:27:03,244 --> 06:27:04,212 TALKING ABOUT THE WONDERS ON THE 8514 06:27:04,212 --> 06:27:06,314 OTHER SIDE OF TRANSFORMATIVE 8515 06:27:06,314 --> 06:27:06,547 THERAPY. 8516 06:27:06,547 --> 06:27:07,548 I THINK IT'S A WONDERFUL MESSAGE 8517 06:27:07,548 --> 06:27:15,156 BUT I THINK WE HAVE GOT TO START 8518 06:27:15,156 --> 06:27:18,993 CONTROLLING THE NARRATIVE MORE 8519 06:27:18,993 --> 06:27:22,463 TO PROVIDE A PICTURE OF THE 8520 06:27:22,463 --> 06:27:28,970 GOOD, BAD AND NOT SO GOOD. 8521 06:27:28,970 --> 06:27:33,474 AS WE TALK OF GATHERING 8522 06:27:33,474 --> 06:27:34,609 STANDARDIZED DATA ON THE BIO 8523 06:27:34,609 --> 06:27:36,177 MEDICAL SIDE WE NEED TO LAYER 8524 06:27:36,177 --> 06:27:37,712 THAT DATA AND BUILDING DATABASES 8525 06:27:37,712 --> 06:27:40,314 WHEN WE HAVE 10 PEOPLE, 12 8526 06:27:40,314 --> 06:27:42,250 PEOPLE GOING TO BE HUNDREDS AND 8527 06:27:42,250 --> 06:27:43,217 EVENTUALLY THOUSANDS, WE NEED TO 8528 06:27:43,217 --> 06:27:48,122 MAKE SURE WITHIN THE REGISTRIES 8529 06:27:48,122 --> 06:27:49,423 THAT WE'RE BUILDING WE'RE ALSO 8530 06:27:49,423 --> 06:27:50,424 BUILDING IN THE QUESTION AND 8531 06:27:50,424 --> 06:27:52,493 INFORMATION THAT IS GOING TO 8532 06:27:52,493 --> 06:27:53,928 GIVE A MORE COMPLETE 8533 06:27:53,928 --> 06:27:56,330 PSYCHOSOCIAL PICTURE TO TELL 8534 06:27:56,330 --> 06:28:01,002 MORE OF THESE STORIES IN 8535 06:28:01,002 --> 06:28:01,602 SYSTEMATIC WAYS AS WELL AS 8536 06:28:01,602 --> 06:28:03,471 INDIVIDUAL WAYS TO GET TO BOTH 8537 06:28:03,471 --> 06:28:03,871 PLACES. 8538 06:28:03,871 --> 06:28:06,340 I THINK THAT'S GOING TO BE 8539 06:28:06,340 --> 06:28:09,911 IMPORTANT SO THAT BOTH PEOPLE 8540 06:28:09,911 --> 06:28:10,912 LIVING WITH SICKLE CELL DISEASE 8541 06:28:10,912 --> 06:28:13,281 CAN MAKE FULLY INFORMED DECISION 8542 06:28:13,281 --> 06:28:14,816 AND HEALTH CARE PROVIDERS CAN 8543 06:28:14,816 --> 06:28:16,551 INFORM THEM THROUGH SHARED 8544 06:28:16,551 --> 06:28:18,219 DECISION MAKING. 8545 06:28:18,219 --> 06:28:21,455 >> IS THERE A QUESTION IN THE 8546 06:28:21,455 --> 06:28:21,856 AUDIENCE? 8547 06:28:21,856 --> 06:28:23,658 >> I'M HAVE ST. JUDE. 8548 06:28:23,658 --> 06:28:27,562 SO MY QUESTION IS NOW THAT 8549 06:28:27,562 --> 06:28:30,097 EDUCATION FOR FAMILIES ABOUT 8550 06:28:30,097 --> 06:28:32,733 SICKLE CELL START AT NEWBORN 8551 06:28:32,733 --> 06:28:33,000 SCREENING. 8552 06:28:33,000 --> 06:28:35,303 DOES INITIATING A CONVERSATION 8553 06:28:35,303 --> 06:28:36,537 AROUND TRANSFORMATIVE THERAPY 8554 06:28:36,537 --> 06:28:42,844 LIKE THE INITIAL CARE FOR THE 8555 06:28:42,844 --> 06:28:47,949 PATIENT IS THAT HELPFUL 8556 06:28:47,949 --> 06:28:48,583 INITIATING THE DISCUSSION THERE 8557 06:28:48,583 --> 06:28:58,860 IS THIS OPTION. 8558 06:29:16,978 --> 06:29:27,088 [NO AUDIO] 8559 06:29:32,226 --> 06:29:33,694 >> I THINK THAT WOULD COME FROM 8560 06:29:33,694 --> 06:29:36,264 THE DISCUSSION. 8561 06:29:36,264 --> 06:29:39,400 MY CHILD DOESN'T HAVE IT BUT I 8562 06:29:39,400 --> 06:29:40,801 DO AND I IMAGINE RECEIVING THE 8563 06:29:40,801 --> 06:29:42,603 INFORMATION AT THE NEWBORN 8564 06:29:42,603 --> 06:29:44,005 SCREENING AND SLIGHTLY FREAKING 8565 06:29:44,005 --> 06:29:44,171 OUT. 8566 06:29:44,171 --> 06:29:46,674 I THINK THAT WOULD BECOME A 8567 06:29:46,674 --> 06:29:48,910 CONVERSATION AS YOU'RE A NEW 8568 06:29:48,910 --> 06:29:50,778 PARENTS WITH A SICKLE CELL CHILD 8569 06:29:50,778 --> 06:29:59,320 GOING TO THE HEMATOLOGIST. 8570 06:29:59,320 --> 06:30:00,554 I DON'T KNOW IF IT'S SOMETHING 8571 06:30:00,554 --> 06:30:03,024 YOU WANT TO BRING UP, HI, YOUR 8572 06:30:03,024 --> 06:30:05,626 NEWBORN HAS SICKLE CELL AND LAY 8573 06:30:05,626 --> 06:30:08,996 OUT NEW TRANSFORMATIVE 8574 06:30:08,996 --> 06:30:09,263 THERAPIES. 8575 06:30:09,263 --> 06:30:10,231 I THINK IT'S A LOT OF 8576 06:30:10,231 --> 06:30:10,765 INFORMATION AT ONCE. 8577 06:30:10,765 --> 06:30:13,534 THAT'S MY OPINION AS A PARENT 8578 06:30:13,534 --> 06:30:14,769 AND WARRIOR MYSELF. 8579 06:30:14,769 --> 06:30:18,539 I WOULD THINK ADRIENNE CAN 8580 06:30:18,539 --> 06:30:19,140 ANSWER BETTER BECAUSE SHE'S A 8581 06:30:19,140 --> 06:30:29,283 MOTHER. 8582 06:30:33,921 --> 06:30:39,427 >> THERE'S A COUPLE TYPES OF 8583 06:30:39,427 --> 06:30:40,528 MOTHERS. 8584 06:30:40,528 --> 06:30:46,500 SOME WHO HUNT DOWN DOCTORS AND 8585 06:30:46,500 --> 06:30:48,970 SCIENTISTS AND EMBARRASS 8586 06:30:48,970 --> 06:30:50,504 THEMSELVES AND THOSE WHO 8587 06:30:50,504 --> 06:30:52,740 POLITELY ASK FOR INFORMATION. 8588 06:30:52,740 --> 06:30:53,574 BECAUSE SICKLE CELL AND I 8589 06:30:53,574 --> 06:30:56,243 REPRESENT FIVE GENERATIONS OF 8590 06:30:56,243 --> 06:30:56,477 MOTHERS. 8591 06:30:56,477 --> 06:31:01,882 I HAVE A LOT OF HISTORY ON MY 8592 06:31:01,882 --> 06:31:02,083 BACK. 8593 06:31:02,083 --> 06:31:06,554 WHAT I'M SEEING NOW GETTING THAT 8594 06:31:06,554 --> 06:31:08,923 LETTER RATHER THAN WRITING A 8595 06:31:08,923 --> 06:31:10,825 DEATH SENTENCE FOR YOUR CHILD 8596 06:31:10,825 --> 06:31:12,526 WHICH IS PRETTY MUCH WHAT MY 8597 06:31:12,526 --> 06:31:14,128 MOTHER GOT AND I GOT. 8598 06:31:14,128 --> 06:31:16,831 YOU'RE OPENED UP TO A WORLD OF 8599 06:31:16,831 --> 06:31:17,231 POSSIBILITIES. 8600 06:31:17,231 --> 06:31:19,467 I THINK THE BIGGEST PART I WOULD 8601 06:31:19,467 --> 06:31:25,206 SAY IS THAT WE HAVE TO MAKE SURE 8602 06:31:25,206 --> 06:31:27,842 THE PEDIATRICIANS ARE TRAINED 8603 06:31:27,842 --> 06:31:29,510 STRAIGHT AWAY TO HAVE THAT 8604 06:31:29,510 --> 06:31:30,644 DISCUSSION AND WE REALLY HAVE TO 8605 06:31:30,644 --> 06:31:34,081 DEPEND ON THEM TO DO IT. 8606 06:31:34,081 --> 06:31:35,182 EVEN THOUGH IN THE PAST I KNOW 8607 06:31:35,182 --> 06:31:37,585 THEY DIDN'T LIKE TALKING TO 8608 06:31:37,585 --> 06:31:39,186 PARENTS ABOUT IT BECAUSE WHO 8609 06:31:39,186 --> 06:31:42,656 WANTS TO TELL SOMEBODY THEIR 8610 06:31:42,656 --> 06:31:44,525 NEWBORN CHILD MAY NOT LIVE. 8611 06:31:44,525 --> 06:31:54,869 THAT'S HOW TO START. 8612 06:32:01,108 --> 06:32:03,444 >> THE LIGHT AT THE END OF THE 8613 06:32:03,444 --> 06:32:03,677 TUNNEL. 8614 06:32:03,677 --> 06:32:09,884 >> AND I WAJT TO -- WANT TO PUT 8615 06:32:09,884 --> 06:32:11,452 IN A PLUG THERE'S IN TRUSTED 8616 06:32:11,452 --> 06:32:12,853 SOURCES NOW AND WE HAVE TO TELL 8617 06:32:12,853 --> 06:32:15,122 PEOPLE AND GID THEM TO THE 8618 06:32:15,122 --> 06:32:16,991 AGENCY -- GUIDE THEM TO THE 8619 06:32:16,991 --> 06:32:19,460 AGENCIES, RESEARCH CENTERS AND 8620 06:32:19,460 --> 06:32:20,094 COMMUNITY-BASED ORGANIZATIONS 8621 06:32:20,094 --> 06:32:23,330 WHICH ARE DOING A GREAT JOB OF 8622 06:32:23,330 --> 06:32:24,131 HOLDING THE COMMUNITY. 8623 06:32:24,131 --> 06:32:26,767 I THINK WE HAVE TO TRY TO 8624 06:32:26,767 --> 06:32:28,969 COUNTER SOME OF THE STUFF THEY 8625 06:32:28,969 --> 06:32:30,738 MAY FIND ON THE INTERNET AND 8626 06:32:30,738 --> 06:32:36,477 TALK AMONG OURSELVES ABOUT THE 8627 06:32:36,477 --> 06:32:37,478 IMPORTANCE OF GETTING YOUR 8628 06:32:37,478 --> 06:32:38,045 INFORMATION FROM A TRUSTED 8629 06:32:38,045 --> 06:32:44,051 SOURCE. 8630 06:32:44,051 --> 06:32:50,257 >> I HAVE A QUESTION. 8631 06:32:50,257 --> 06:32:52,793 I'M VERY EXCITED ABOUT SOMETHING 8632 06:32:52,793 --> 06:33:01,435 I HEARD JULIE SAY ABOUT 8633 06:33:01,435 --> 06:33:11,612 APHERESIS. 8634 06:33:11,946 --> 06:33:16,484 AND I GUESS I WANT TO SAY I 8635 06:33:16,484 --> 06:33:17,518 THINK WHOEN I TALK ABOUT LESSONS 8636 06:33:17,518 --> 06:33:18,752 LEARNED THAT'S ONE OF THE THINGS 8637 06:33:18,752 --> 06:33:21,155 I'M LOOKING AT. 8638 06:33:21,155 --> 06:33:22,790 THOSE EXAMPLES OF THINGS WE 8639 06:33:22,790 --> 06:33:24,291 ALREADY HAVE ACCESS TO THAT 8640 06:33:24,291 --> 06:33:27,128 WHILE WE'RE IN THE IN BETWEEN 8641 06:33:27,128 --> 06:33:29,663 TIME WE'RE MAKING CELL THERAPY 8642 06:33:29,663 --> 06:33:30,164 AVAILABLE. 8643 06:33:30,164 --> 06:33:32,099 WHAT THINGS CAN WE BE PUTTING IN 8644 06:33:32,099 --> 06:33:34,802 PLACE SO THAT PEOPLE ARE LIVING 8645 06:33:34,802 --> 06:33:37,771 BETTER AND HAVING HEALTHIER 8646 06:33:37,771 --> 06:33:40,608 BODIES AS WE'RE MOVING MORE 8647 06:33:40,608 --> 06:33:44,512 TOWARDS ACCESS TO THE CURRENT. 8648 06:33:44,512 --> 06:33:49,917 CAN YOU TALK ABOUT THAT A LITTLE 8649 06:33:49,917 --> 06:33:50,084 BIT. 8650 06:33:50,084 --> 06:33:50,384 >> SURE. 8651 06:33:50,384 --> 06:33:53,120 THERE'S MANY PARTS TO UNPACK TO 8652 06:33:53,120 --> 06:33:53,487 THAT. 8653 06:33:53,487 --> 06:33:55,723 ONE OF THE FIRST PARTS TO UNPACK 8654 06:33:55,723 --> 06:33:58,826 IS WHEN TO TRANSFUSE, HOW TO 8655 06:33:58,826 --> 06:34:00,594 TRANSFUSE AND WHEN TO DO RED 8656 06:34:00,594 --> 06:34:02,596 CELL EXCHANGE AND HOW TO DO THE 8657 06:34:02,596 --> 06:34:03,297 RED CELL EXCHANGE. 8658 06:34:03,297 --> 06:34:08,302 WHAT I MEAN BY THAT IS WHAT 8659 06:34:08,302 --> 06:34:10,571 PATIENTS RED CELL EXCHANGE IS 8660 06:34:10,571 --> 06:34:13,073 GOOD FOR WHAT TIME BECAUSE IT 8661 06:34:13,073 --> 06:34:18,779 CAN INVOLVE A COMMITMENT. 8662 06:34:18,779 --> 06:34:20,481 TAKING AN OVERVIEW OF THE WHOLE 8663 06:34:20,481 --> 06:34:24,518 PROCESS I WOULD SAY THERE'S A 8664 06:34:24,518 --> 06:34:28,789 LOT OF ROOM TO IMPROVE ON HOW WE 8665 06:34:28,789 --> 06:34:30,391 DO RED CELL EXCHANGE AND 8666 06:34:30,391 --> 06:34:32,059 THERAPIES FOR PATIENTS WITH 8667 06:34:32,059 --> 06:34:32,726 SICKLE CELL. 8668 06:34:32,726 --> 06:34:34,995 A LOT OF THE TOOLS AND 8669 06:34:34,995 --> 06:34:36,964 INSTRUMENTS WERE NEVER BUILT FOR 8670 06:34:36,964 --> 06:34:38,432 PARTICIPANTS WITH SICKLE CELL. 8671 06:34:38,432 --> 06:34:41,902 I BROUGHT UP DURING THE SLIDES I 8672 06:34:41,902 --> 06:34:47,508 PRESENTED THAT MAYBE CATHETERS, 8673 06:34:47,508 --> 06:34:50,411 PORTS, WHATEVER WE NEED TO DO 8674 06:34:50,411 --> 06:34:53,147 RED CELL EXCHANGE, IT REALLY 8675 06:34:53,147 --> 06:34:54,748 HASN'T BEEN THOUGHT ABOUT WITH 8676 06:34:54,748 --> 06:34:57,017 HOW COULD WE DO THIS BETTER FOR 8677 06:34:57,017 --> 06:34:58,419 A PATIENT WITH SICKLE CELL 8678 06:34:58,419 --> 06:35:00,654 DISEASE AND HOW COULD WE DO IT 8679 06:35:00,654 --> 06:35:06,627 BETTER SO I THINK IT'S IMPORTANT 8680 06:35:06,627 --> 06:35:09,930 OVER ALL SO I DO THINK IT'S 8681 06:35:09,930 --> 06:35:11,198 IMPORTANT TO PUT PRESSURE ON 8682 06:35:11,198 --> 06:35:16,470 MANUFACTURERS TO IMPROVE THAT. 8683 06:35:16,470 --> 06:35:22,910 IN TERMS OF A MATTER OF 8684 06:35:22,910 --> 06:35:23,177 EDUCATION. 8685 06:35:23,177 --> 06:35:25,379 THE MORE WE DISCUSS THERE'S AN 8686 06:35:25,379 --> 06:35:27,548 OPTION THE MORE THAT WE BRING 8687 06:35:27,548 --> 06:35:30,084 INTO HEMATOLOGY TO TRANSPLANT 8688 06:35:30,084 --> 06:35:32,486 THAT THERE ARE SPECIALISTS AND 8689 06:35:32,486 --> 06:35:36,156 THE MORE WE TRAIN NURSING AND 8690 06:35:36,156 --> 06:35:38,993 PHYSICIANS IF APHERESIS IS MORE 8691 06:35:38,993 --> 06:35:40,294 THAN A PROCEDURE. 8692 06:35:40,294 --> 06:35:43,030 THINK ABOUT THE SCIENCE 8693 06:35:43,030 --> 06:35:47,401 BYPRODUCT -- SCIENCE BEHIND IT 8694 06:35:47,401 --> 06:35:49,503 AND THE IMPACT AND THEN YOU CAN 8695 06:35:49,503 --> 06:35:52,273 APPROACH THE PATIENT MORE THAN 8696 06:35:52,273 --> 06:35:53,107 JUST THE THREE HOUR PROCEDURE 8697 06:35:53,107 --> 06:35:59,580 AND PUT IT IN THE CONTEXT OF 8698 06:35:59,580 --> 06:36:02,416 HERE'S HOW IT CAN IMPROVE OR 8699 06:36:02,416 --> 06:36:03,150 STABILIZE YOUR DISEASE. 8700 06:36:03,150 --> 06:36:04,752 >> THANK YOU SO MUCH. 8701 06:36:04,752 --> 06:36:08,856 I WANT TO SAY THANK YOU TO THE 8702 06:36:08,856 --> 06:36:11,725 PANEL WHO CAME UP AND SPOKE, 8703 06:36:11,725 --> 06:36:14,395 DR. CECELIA VALRIE AND 8704 06:36:14,395 --> 06:36:16,530 DR. PORTER AND DR. MANIS. 8705 06:36:16,530 --> 06:36:18,065 THANK YOU ALL. 8706 06:36:18,065 --> 06:36:21,435 I BELIEVE WE'RE GETTING OUT OF 8707 06:36:21,435 --> 06:36:21,635 HERE. 8708 06:36:21,635 --> 06:36:23,504 >> THANK YOU SO MUCH. 8709 06:36:23,504 --> 06:36:27,174 THIS IS A GREAT DISCUSSION. 8710 06:36:27,174 --> 06:36:37,718 SO, WE'RE ADJOURNED FOR THE DAY. 8711 06:36:43,557 --> 06:36:45,025 WE'RE ADJOURNING FOR THE DAY 8712 06:36:45,025 --> 06:36:46,293 TODAY BUT WE'LL BE BACK 8713 06:36:46,293 --> 06:36:46,560 TOMORROW. 8714 06:36:46,560 --> 06:36:52,499 WE HAVE A GREAT SESSION FOR 8715 06:36:52,499 --> 06:36:55,669 TOMORROW THAT STARTS WITH GLOBAL 8716 06:36:55,669 --> 06:36:57,171 PERSPECTIVE OF SICKLE CELL FROM 8717 06:36:57,171 --> 06:37:00,841 DIFFERENT COUNTRIES. 8718 06:37:00,841 --> 06:37:03,610 I THINK IT WILL BE A VERY 8719 06:37:03,610 --> 06:37:08,482 INTERESTING CONVERSATION AND 8720 06:37:08,482 --> 06:37:09,883 HAVE TALKS ABOUT CDC AND PAIN 8721 06:37:09,883 --> 06:37:10,517 AND WE'LL SEE YOU ALL TOMORROW. 8722 06:37:10,517 --> 06:37:12,486 THANK YOU. 8723 06:37:12,486 --> 06:37:12,553