Abstract：
UNASSIGNED: In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative-related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on the conditioning protocol. Graft failure occurred in 8 of 70 (11.4%) and only in participants aged <18 years; all had autologous reconstitution. After a median follow-up of 2.4 years, the 2-year Kaplan-Meier-based probability of event-free survival was 82.6%. The 2-year overall survival was 94.1%, with no difference between children and adult participants. After excluding participants with graft failure (n = 8), participants with engraftment had median whole blood donor chimerism values at days +180 and +365 after transplant of 100% (n = 58), respectively, and 96.6% (57/59) were off immunosuppression 1 year after transplant. The 1-year grade 3 to 4 acute graft-versus-host disease (GVHD) rate was 10%, and the 2-year moderate-severe chronic GVHD rate was 10%. Five participants (7.1%) died from infectious complications. We demonstrate that nonmyeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, compared to the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates. The trial was registered at www.clinicaltrials.gov as #NCT01850108.
摘要：
在学习协作的环境中，我们进行了一项国际多中心2期临床试验,验证了以下假设:非清髓相关的单倍相合BMT与噻替帕和移植后环磷酰胺(PTCy)的2年无事件生存率(无移植失败或死亡)至少达到80%.共有70名参与者（中位年龄19.1（IQR14.1-25.0）可根据条件方案进行评估。移植失败发生率为11.4%（8/70），仅在<18岁的参与者中发生（p=0.001）；所有参与者都进行了自体重建。经过2.4年的中位随访（IQR1.5-3.9），基于Kaplan-Meier的2年无事件生存率为82.6%(95%CI71.4%-89.7%).2年总生存率为94.1％（95％CI84.9％-97.7％），儿童和成人参与者之间没有差异（p=0.889）。在排除移植失败的参与者(n=8)后，移植参与者在移植后D+180和D+365的中位全血供体嵌合体值为100.0%(IQR99.8-100.0%;n=59)和100.0%(IQR100.0-100.0%;n=58)，分别,96.6%(57/59)的患者在移植后1年出现免疫抑制。1年III-IV级急性移植物抗宿主病（GvHD）的发生率为10.0％（95％CI4.6-18.6％），2年中重度慢性GvHD发生率为10.0％（95％CI4.6-18.6％）。五名参与者（7.1％）死于感染性并发症。我们证明，非清髓性单倍体BMT与thiotepa和PTCy是大多数成年人容易获得的治疗方法，即使是那些器官受损的人，而不是更昂贵的清髓性基因治疗和基因编辑。儿童需要采取其他策略来降低移植物失败率（ClinicalTrials.gov标识符NCT01850108）。
