Background Aplastic anemia (AA) represents a critical hematological disorder, with allogeneic hematopoietic stem cell transplantation (allo-HSCT) serving as a curative intervention for severe AA (SAA). Notably, haploidentical (haplo-) HSCT is increasingly utilized, although the occurrence of chronic graft-versus-host disease (cGvHD) remains a substantial complication. Current literature predominantly addresses cGvHD in the context of matched donor HSCT or malignancies, resulting in a paucity of knowledge regarding its clinical characteristics, risk factors, and impact on survival in SAA patients undergoing haplo-HSCT.

Methods This study aimed to investigate the clinical characteristics, risk factors, and impact of cGvHD on survival in SAA patients after haplo-HSCT. A total of 485 SAA patients who underwent first haplo-HSCT between January 2006 and December 2022 were included, excluding early mortality (within 100 days) and graft rejection. The conditioning regimens employed comprised busulfan/cyclophosphamide with antithymocyte globulin (ATG) with or without fludarabine, while GvHD prophylaxis involved cyclosporine A, methotrexate, and mycophenolate mofetil. Statistical analyses were conducted using the Kaplan-Meier method, log-rank test, and competing risk regression.

Results The study results indicated that 156 patients developed cGvHD, with cumulative incidences of 31.8% at 3 years and 32.0% at 5 years. The most frequently affected organs were the skin (76.9%), oral cavity (26.3%), and liver (14.1%), with 39.1% of patients experiencing multi-organ involvement. Among the patients, 72.4% exhibited mild cGvHD, 17.9% moderate, and 9.6% severe. Multivariate analysis identified independent risk factors for cGvHD as patient age ≥18 years (hazard ratio [HR] 1.42, P = 0.029), maternal donor (HR 1.65, P = 0.018), and a history of grade II–IV acute GvHD (aGvHD, HR 1.70, P = 0.004). For moderate to severe cGvHD, risk factors were age ≥18 years (HR 2.69, P = 0.004) and a history of grade III–IV aGvHD (HR 2.27, P = 0.043). Severe cGvHD was associated with previous ATG treatment (HR 3.09, P = 0.041), female donor to male recipient (HR 3.08, P=0.028), and a history of grade III–IV aGvHD (HR 5.26, P = 0.004). The 5-year OS was 95.0%, with no significant difference between cGvHD and non-cGvHD groups (95.5% vs 94.8%, P = 0.724) or between the moderate to severe cGvHD and non-moderate to severe groups (90.7% vs 95.5%, P = 0.177), but severe cGvHD patients had significantly lower 5-year OS (80.0%) than those with mild (97.3%) or moderate (96.4%) cGvHD (P = 0.007).

Conclusion These findings contribute to understanding cGvHD in SAA patients after haplo-HSCT, aiding in personalized management to improve clinical outcomes.

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2025
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