Walters Mark C, Eapen Mary, Liu Yiwen, El Rassi Fuad, Waller Edmund K, Levine John E, Strouse John J, Antin Joseph H, Parikh Suhag H, Bakshi Nitya, Dampier Carlton, Jaroscak Jennifer J, Bergmann Shayla, Wong Trisha, Kota Vamsi, Pace Betty, Lekakis Lazaros J, Lulla Premal, Nickel Robert S, Kasow Kimberly A, Popat Uday, Smith Wally, Yu Lolie, DiFronzo Nancy, Geller Nancy, Kamani Naynesh, Klings Elizabeth S, Hassell Kathryn, Mendizabal Adam, Sullivan Keith, Neuberg Donna, Krishnamurti Lakshmanan
Department of Pediatrics, Division of Hematology, University of California San Francisco, San Francisco, CA.
Department of Medicine, Division of Hematology-Oncology, Medical College of Wisconsin, Milwaukee, WI.
Blood Adv. 2025 Mar 11;9(5):955-965. doi: 10.1182/bloodadvances.2024013926.
Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2 years after biologic assignment to a donor or no donor (SOC) arm based on the availability of an HLA-matched sibling or unrelated donor (BMT CTN 1503). A donor search was commenced after eligibility confirmation. The primary end point was a comparison of survival between the treatment arms 2 years after biologic assignment. Power calculations required 60 participants in the donor arm and 140 in the no donor arm to determine if early transplant-related mortality might be balanced by disease-related mortality over a longer period of follow-up. Secondary objectives were a comparison of the changes in SCD-related events, functional outcomes, and organ function. The data were analyzed according to the intent-to-treat principle. A total of 113 participants were enrolled with 28 in the donor arm and 85 in the no donor arm. The 2-year probabilities of survival were 89% and 93%, in the donor vs no donor arms. Vaso-occlusive pain (VOC) was less frequent in the donor arm in the second year after biologic assignment (P < .001). Based on PROMIS-57 surveys, there was a decrease in fatigue (P = .003) and an increase in the ability to participate in social roles and activities (P = .003) in the donor arm 2 years after biologic assignment. Differences in other secondary outcomes did not reach statistical significance. Barriers to accrual prevented an objective comparison of survival. Assignment to the donor arm led to improvements in VOC, fatigue, and social function. This trial was registered at www.clinicaltrials.gov as #NCT02766465.
疾病修饰疗法是镰状细胞病（SCD）的标准治疗方法，但造血细胞移植（HCT）具有治愈潜力。我们根据是否有人类白细胞抗原（HLA）匹配的同胞或无关供体（BMT CTN 1503），前瞻性地比较了生物分配至有供体或无供体（标准治疗）组后2年的结局。在确认符合条件后开始寻找供体。主要终点是生物分配后2年治疗组之间的生存比较。功效计算要求供体组有60名参与者，无供体组有140名参与者，以确定早期移植相关死亡率是否可能在更长的随访期内被疾病相关死亡率所平衡。次要目标是比较SCD相关事件、功能结局和器官功能的变化。数据根据意向性治疗原则进行分析。共有113名参与者入组，供体组28名，无供体组85名。供体组与无供体组2年生存率分别为89%和93%。生物分配后第二年，供体组血管闭塞性疼痛（VOC）的发生率较低（P <.001）。根据患者报告结果测量信息系统-57（PROMIS-57）调查，生物分配后2年，供体组疲劳感有所减轻（P =.003），参与社会角色和活动的能力有所提高（P =.003）。其他次要结局的差异未达到统计学意义。入组障碍妨碍了对生存的客观比较。分配至供体组可改善VOC、疲劳和社会功能。该试验已在www.clinicaltrials.gov上注册，注册号为#NCT02766465。
