Abstract：
Haploidentical stem cell transplantation (haplo-SCT) represents the main alternative for children with inherited bone marrow failure syndrome (I-BMF) lacking a matched donor. This retrospective study, conducted on behalf of the EBMT SAAWP and PDWP, aims to report the current outcomes of haplo-SCT in I-BMFs, comparing the different in vivo and ex vivo T-cell depletion approaches. One hundred and sixty-two I-BMF patients who underwent haplo-SCT (median age 7.4 years) have been registered. Fanconi Anemia was the most represented diagnosis (70.1%). Based on different T-cell depletion (TCD) approaches, four categories were identified: (1) TCRαβ+/CD19+-depletion (43.8%); (2) T-repleted with post-transplant Cyclophosphamide (PTCy, 34.0%); (3) In-vivo T-depletion with ATG/alemtuzumab (14.8%); (4) CD34+ positive selection (7.4%). The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 76% respectively, while that of primary and secondary graft failure was 10% and 8% respectively. The 100-day CI of acute GvHD grade III-IV(95% CI) was 13%, while the 24-month CI of extensive chronic GvHD was 4%. After a median follow-up of 43.4 months, the 2-year overall survival(OS) and GvHD/Rejection-free Survival (GRFS) probabilities are 67% and 53%, respectively. The TCR CD3+αβ+/CD19+ depletion group showed a significantly lower incidence of both acute and chronic GvHD and higher OS (79%; p0.013) and GRFS (71%; p < .001), while no significant differences in outcomes have been observed by different diagnosis and conditioning regimens. This large retrospective study supports the safety and feasibility of haplo-SCT in I-BMF patients. TCRαβ+/CD19+ depletion offers higher chances of patients\' survival, with a significantly lower risk of severe a- and c-GvHD in I-BMFs compared to other platforms.
摘要：
单倍体干细胞移植（haplo-SCT）是缺乏匹配供体的遗传性骨髓衰竭综合征（I-BMF）儿童的主要替代方法。这项回顾性研究,代表EBMTSAAWP和PDWP进行，目的是报告I-BMF中haplo-SCT的当前结果，比较不同的体内和离体T细胞消耗方法。已注册了一百六十二例I-BMF患者，他们接受了haplo-SCT（中位年龄7.4岁）。范可尼贫血是最具代表性的诊断(70.1%)。基于不同的T细胞耗竭（TCD）方法，确定了四个类别：（1）TCRαβ/CD19耗竭（43.8％）；（2）移植后环磷酰胺（PTCy，34.0%）；（3）ATG/阿仑珠单抗体内T-耗竭（14.8%）；（4）CD34+阳性选择（7.4%）。中性粒细胞和血小板植入的累积发生率（CI）分别为84％和76％，而原发性和继发性移植物失败的发生率分别为10％和8％。急性GvHDIII-IV级（95％CI）的100天CI为13％，而广泛慢性GvHD的24个月CI为4%。在中位随访43.4个月后，2年总生存率（OS）和GvHD/无排斥生存（GRFS）概率分别为67％和53％，分别。TCRCD3+αβ+/CD19+耗竭组的急性和慢性GvHD发病率显著降低，OS(79%;p0.013)和GRFS(71%;p<.001)较高，而不同的诊断和预处理方案在结局方面没有观察到显著差异.这项大型回顾性研究支持I-BMF患者中haplo-SCT的安全性和可行性。TCRαβ+/CD19+耗竭提供了更高的患者生存机会，与其他平台相比，I-BMF中严重的a-和c-GvHD的风险显着降低。
