Abstract：
A significant complication of HSCT is graft failure, although few studies focus on this problem in patients with inborn errors of immunity (IE). We explored outcome of second HSCT for IEI by a retrospective, single-centre study between 2002 and 2022. Four hundred ninety-three patients underwent allogeneic HSCT for severe combined immunodeficiency (SCID; n = 113, 22.9%) or non-SCID IEI (n = 380, 77.1%). Thirty patients (6.0%) required second HSCT. Unconditioned infusion or no serotherapy at first HSCT was more common in patients who required second transplant. Median interval between first and second HSCT was 0.97 years (range: 0.19-8.60 years); a different donor was selected for second HSCT in 24/30 (80.0%) patients. Conditioning regimens for second HSCT were predominately treosulfan-based (with thiotepa: n = 18, 60.0%; without, n = 6, 20.0%). Patients received grafts from peripheral blood stem cell (n = 25, 83.3%) or bone marrow (n = 5, 16.7%) with median stem cell dose 9.5 × 106 CD34 + cells/kilogram (range: 1.4-32.3). Median follow-up was 1.92 years (0.22-16.0). Overall survival was 80.8% and event-free survival was 64.7%. Four patients died, two of early-transplant related complications, and two of late sepsis post-second HSCT. Three patients required third HSCT; all are alive with 100% donor chimerism. Cumulative incidence of acute graft-versus-host disease was 28.4%, (all grade I-II). Viral reactivation was seen in 13/30 (43.3%) patients, including HHV6 (n = 6), CMV (n = 4), and adenovirus (n = 2). At latest follow-up, 25/26 surviving patients have donor chimerism ≥ 90% and 16/25 (64.0%) have discontinued immunoglobulin replacement. Second HSCT offers IEI patients with graft failure curative treatment with good overall survival and immunological recovery.
摘要：
HSCT的一个重要并发症是移植失败，尽管很少有研究关注先天性免疫错误（IE）患者的这一问题。我们通过回顾性研究探讨了IEI第二次HSCT的结果，2002年至2022年之间的单中心研究。493例患者因严重的联合免疫缺陷（SCID；n=113，22.9％）或非SCIDIEI（n=380，77.1％）接受了同种异体HSCT。30例患者（6.0％）需要第二次HSCT。第一次HSCT时无条件输注或无血清治疗在需要第二次移植的患者中更为常见。第一次和第二次HSCT之间的中位间隔为0.97年（范围：0.19-8.60年）；在24/30（80.0％）的患者中，选择了不同的供体进行第二次HSCT。第二次HSCT的调理方案主要是基于曲硫丹的（带有噻替帕：n=18，60.0％；没有，n=6,20.0%)。患者接受外周血干细胞（n=25，83.3％）或骨髓（n=5，16.7％）移植，中位干细胞剂量为9.5×106CD34细胞/千克（范围：1.4-32.3）。中位随访时间为1.92年(0.22-16.0)。总生存率为80.8%，无事件生存率为64.7%。四名病人死亡,两种早期移植相关的并发症，和两个晚期脓毒症后第二次HSCT。三名患者需要第三次HSCT；所有患者均存活，具有100％的供体嵌合状态。急性移植物抗宿主病的累积发病率为28.4%,（所有I-II级）。在13/30（43.3％）患者中观察到病毒再激活，包括HHV6（n=6），CMV（n=4），和腺病毒(n=2)。在最新的随访中，25/26存活患者的供体嵌合体≥90％，16/25（64.0％）停止了免疫球蛋白替代。第二次HSCT为IEI患者提供移植失败的治愈性治疗，具有良好的总体生存率和免疫恢复。
