Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Paediatric Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
Blood. 2022 Mar 31;139(13):2066-2079. doi: 10.1182/blood.2021014687.
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.
异基因造血干细胞移植（HSCT）是治疗威斯科特-奥尔德里奇综合征（WAS）患者的潜在根治方法。随着时间的推移，总体生存率方面的 HSCT 结果有所改善，但一些研究已经确定，年龄较大和来自替代供体的 HSCT 是预测较差结果的风险因素。我们分析了 2006 年至 2017 年期间在欧洲血液和骨髓移植学会中心接受移植的 197 名患者，他们接受了先天错误工作组（IEWP）推荐的预处理：要么是白消安（n = 103），要么是曲奥沙胺（n = 94）联合氟达拉滨±噻替哌。HSCT 后中位随访时间为 44.9 个月时，176 名患者存活，3 年总生存率为 88.7%，无慢性移植物抗宿主病（GVHD）生存（包括死亡、移植物失败和严重慢性 GVHD）为 81.7%。总体生存率和无慢性 GVHD 生存不受预处理方案（白消安与曲奥沙胺）、供体类型（匹配同胞供体/匹配家族供体与匹配无关供体/不匹配无关供体与不匹配家族供体）或 HSCT 时间（2006-2013 年与 2014-2017 年）的影响。HSCT 时年龄<5 岁的患者总体生存率显著提高。III 级至 IV 级急性 GVHD 和广泛/中度/重度慢性 GVHD 的总累积发生率分别为 6.6%和 2.1%。接受曲奥沙胺预处理的患者移植失败和混合供体嵌合体的发生率更高，更频繁地接受二次手术（二次 HSCT、未预处理干细胞增强、供体淋巴细胞输注或脾切除术）。总之，采用 IEWP 目前推荐的预处理方案进行 WAS 的 HSCT 可获得极好的生存率和低 GVHD 发生率，与供体或干细胞来源无关，但年龄≥5 岁仍然是总体生存率的一个风险因素。
