OBJECTIVE: This study sought to characterize HCT outcomes in APDS.
METHODS: Retrospective data were collected on 57 patients with APDS1/2 (median age, 13 years; range, 2-66 years) who underwent HCT.
RESULTS: Pre-HCT comorbidities such as lung, gastrointestinal, and liver pathology were common, with hematologic malignancy in 26%. With median follow-up of 2.3 years, 2-year overall and graft failure-free survival probabilities were 86% and 68%, respectively, and did not differ significantly by APDS1 versus APDS2, donor type, or conditioning intensity. The 2-year cumulative incidence of graft failure following first HCT was 17% overall but 42% if mammalian target of rapamycin inhibitor(s) (mTORi) were used in the first year post-HCT, compared with 9% without mTORi. Similarly, 2-year cumulative incidence of unplanned donor cell infusion was overall 28%, but 65% in the context of mTORi receipt and 23% without. Phenotype reversal occurred in 96% of evaluable patients, of whom 17% had mixed chimerism. Vulnerability to renal complications continued post-HCT, adding new insights into potential nonimmunologic roles of phosphoinositide 3-kinase not correctable through HCT.
CONCLUSIONS: Graft failure, graft instability, and poor graft function requiring unplanned donor cell infusion were major barriers to successful HCT. Post-HCT mTORi use may confer an advantage to residual host cells, promoting graft instability. Longer-term post-HCT follow-up of more patients is needed to elucidate the kinetics of immune reconstitution and donor chimerism, establish approaches that reduce graft instability, and assess the completeness of phenotype reversal over time.
目的:本研究旨在表征APDS的HCT结局。
方法:收集57例APDS1/2患者的回顾性资料(中位年龄,13年;范围,2-66岁)接受HCT。
结果:HCT前合并症,例如肺,胃肠,肝脏病理很常见,血液系统恶性肿瘤占26%。中位随访时间为2.3年,2年总体和无移植物失败的生存概率分别为86%和68%,分别,APDS1与APDS2,供体类型没有显着差异,或调理强度。首次HCT后移植失败的2年累积发生率为17%,但如果在HCT后的第一年使用哺乳动物雷帕霉素抑制剂(mTORi),则为42%。与没有mTOri的9%相比。同样,非计划供体细胞输注的2年累计发生率为28%,但65%在mTOri收据的情况下,23%没有。表型逆转发生在96%的可评估患者中,其中17%有混合嵌合体。HCT后肾脏并发症的脆弱性持续存在,增加了对不能通过HCT纠正的磷酸肌醇3激酶的潜在非免疫作用的新见解。
结论:移植失败,移植物不稳定性,移植物功能差需要非计划的供体细胞输注是HCT成功的主要障碍。HCT后mTORi的使用可能会给残留的宿主细胞带来优势,促进移植物不稳定性。需要对更多患者进行更长期的HCT后随访,以阐明免疫重建和供体嵌合体的动力学,建立减少移植物不稳定性的方法,并评估表型逆转随时间的完整性。