Albert Michael H, Sirait Tiarlan, Eikema Dirk-Jan, Bakunina Katerina, Wehr Claudia, Suarez Felipe, Fox Maria Laura, Mahlaoui Nizar, Gennery Andrew R, Lankester Arjan C, Beier Rita, Bernardo Maria Ester, Bigley Venetia, Lindemans Caroline A, Burns Siobhan O, Carpenter Ben, Dybko Jaroslaw, Güngör Tayfun, Hauck Fabian, Lum Su Han, Balashov Dmitry, Meisel Roland, Moshous Despina, Schulz Ansgar, Speckmann Carsten, Slatter Mary A, Strahm Brigitte, Uckan-Cetinkaya Duygu, Meyts Isabelle, Vallée Tanja C, Wynn Robert, Neven Bénédicte, Morris Emma C, Aiuti Alessandro, Maschan Alexei, Aljurf Mahmoud, Gedde-Dahl Tobias, Gurman Gunhan, Bordon Victoria, Kriván Gergely, Locatelli Franco, Porta Fulvio, Valcárcel David, Beguin Yves, Faraci Maura, Kröger Nicolaus, Kulagin Aleksandr, Shaw Peter J, Veelken Joan Hendrik, Diaz de Heredia Cristina, Fagioli Franca, Felber Matthias, Gruhn Bernd, Holter Wolfgang, Rössig Claudia, Sedlacek Petr, Apperley Jane, Ayas Mouhab, Bodova Ivana, Choi Goda, Cornelissen J J, Sirvent Anne, Khan Anjum, Kupesiz Alphan, Lenhoff Stig, Ozdogu Hakan, von der Weid Nicolas, Rovira Montserrat, Schots Rik, Vinh Donald C
Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany.
Statistical Unit and Data Office, European Society for Blood and Marrow Transplantation (EBMT), Leiden, The Netherlands.
Blood. 2022 Oct 6;140(14):1635-1649. doi: 10.1182/blood.2022015506.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT.
异基因造血干细胞移植（HSCT）是治疗许多先天性免疫缺陷（IEI）婴幼儿的金标准治愈性疗法，但患有IEI的青少年和成人很少被转诊接受移植。除了小型单中心研究外，缺乏已发表的HSCT结果数据，以及认为移植相关死亡率高，这使得针对在生命后期出现或发展为严重器官损害的IEI患者采用HSCT治疗有所延迟。这项大型回顾性多中心HSCT结果研究报告了329例IEI患者（HSCT时年龄范围为15 - 62.5岁）。患者在2000年至2019年间接受了首次HSCT。主要终点是总生存期（OS）和无事件生存期（EFS）。我们还评估了HSCT时IEI亚组和IEI特异性风险因素的影响，包括感染、支气管扩张、结肠炎、恶性肿瘤、炎症性肺病、脾切除术、肝功能障碍和全身免疫抑制。在中位随访44.3个月时，所有患者HSCT后1年和5年的估计OS分别为78%和71%，EFS分别为65%和62%，严重急性移植物抗宿主病（8%）或广泛慢性移植物抗宿主病（7%）的发生率较低。单因素分析显示，原发性抗体缺陷、支气管扩张、既往脾切除术、肝脏合并症以及造血细胞移植合并症指数评分较高的患者，OS和EFS较差。多变量分析显示，IEI相关并发症数量较多的患者EFS较差。年龄和供体对OS或EFS均无显著影响。我们已经确定了与年龄无关的不良结局风险因素，为确定哪些患者最有可能从HSCT中获益提供了急需的证据。
