Unrelated donor hematopoietic stem cell transplantation (URD-HSCT) is a curative option for severe aplastic anemia (SAA), but the optimal conditioning regimen remains unclear. This retrospective study compares Busulfan/Cyclophosphamide/Anti-thymocyte globulin (Bu/Cy/ATG) and Fludarabine/Cyclophosphamide/Anti-thymocyte globulin (Flu/Cy/ATG) protocols to identify the best regimen for SAA patients. We retrospectively analyzed the clinical outcomes of 107 SAA patients who underwent URD-HSCT with Flu/Cy/ATG (n=63) or Bu/Cy/ATG (n=44) between November 2012 and December 2022. No significant differences were observed in the cumulative incidence of neutrophil/platelet engraftment, graft failure, graft-versus-host disease (GVHD), or CMV viremia. Overall survival (OS) at 7 years was 95.5% (95% CI: 89.5-100) with Bu/Cy/ATG vs. 85.5% (95% CI: 77.1-94.7) with Flu/Cy/ATG, and failure-free survival (FFS) at 7 years was 95.5% (95% CI: 89.5-100) versus 83.9% (95% CI: 75.2-93.6). Multivariate analysis identified Bu/Cy/ATG protocol as favorable for OS (Hazard ratio, HR 0.122, 95% CI: 0.021-0.715, P = 0.020) and FFS (HR 0.090, 95% CI: 0.015-0.538, P = 0.008). Moreover, multivariate analysis confirmed that the Bu/Cy/ATG regimen significantly reduced the risk of EBV viremia (Relative risk, RR 0.175, 95% CI: 0.026-0.717, P = 0.032) and post-transplant lymphoproliferative disorder (RR 0.031, 95% CI: 0-0.536, P = 0.012). Subgroup analysis through multivariate modeling further demonstrated that the Bu/Cy/ATG regimen demonstrated superior OS, FFS and EBV infection outcomes in patients older than 30 years. The Bu/Cy/ATG regimen, compared to Flu/Cy/ATG protocol, offers superior outcomes, including improved OS/FFS and reduced EBV infection, suggesting it may be the preferred choice for SAA patients undergoing URD-HSCT, especially for patients older than 30 years. Larger cohorts and prospective trials are needed to validate these findings.

Keywords: Bu/Cy/ATG; Flu/Cy/ATG; aplastic anemia; unrelated stem cell transplantation.

Copyright © 2025. Published by Elsevier Inc.

无关供者造血干细胞移植（URD-HSCT）是治疗严重再生障碍性贫血（SAA）的一种根治选择，但最佳预处理方案尚不清楚。本回顾性研究比较了Busulfan/Cyclophosphamide/Anti-thymocyte globulin (Bu/Cy/ATG) 和 Fludarabine/Cyclophosphamide/Anti-thymocyte globulin (Flu/Cy/ATG) 方案，以确定SAA患者的最佳方案。我们回顾性分析了2012年11月至2022年12月期间接受URD-HSCT并采用Flu/Cy/ATG（n=63）或Bu/Cy/ATG（n=44）方案的107例SAA患者的临床结果。在中性粒细胞/血小板植入、移植物失败、移植物抗宿主病（GVHD）和CMV病毒血症的累积发病率方面没有观察到显著差异。Bu/Cy/ATG方案与Flu/Cy/ATG方案相比，7年总体生存率(OS)分别为95.5% (95% CI: 89.5-100) 和 85.5% (95% CI: 77.1-94.7)，无失败生存率(FFS) 分别为95.5% (95% CI: 89.5-100) 和83.9% (95% CI: 75.2-93.6)。多因素分析表明，Bu/Cy/ATG方案有利于OS（风险比HR 0.122, 95% CI: 0.021-0.715, P = 0.020）和FFS（HR 0.090, 95% CI: 0.015-0.538, P = 0.008）。此外，多因素分析证实Bu/Cy/ATG方案显著降低了EBV病毒血症的风险（相对风险RR 0.175, 95% CI: 0.026-0.717, P = 0.032）和移植后淋巴增生性疾病的发生率（RR 0.031, 95% CI: 0-0.536, P = 0.012）。通过多变量建模进行的亚组分析进一步表明，Bu/Cy/ATG方案在30岁以上患者中表现出更优的OS、FFS和EBV感染结果。与Flu/Cy/ATG方案相比，Bu/Cy/ATG方案提供了更好的结局，包括提高OS和FFS以及减少EBV感染，这表明它可能是接受URD-HSCT的SAA患者的优选方案，特别是对于30岁以上的患者。需要更大规模的队列研究和前瞻性试验来验证这些发现。

关键词：
Bu/Cy/ATG；Flu/Cy/ATG；再生障碍性贫血；无关供者干细胞移植。

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