Novel insights from a large cohort: Elucidating incidence, risk factors, treatment, and prognostic predictors in autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation

Abstract Background and Objectives Autoimmune hemolytic anemia (AIHA) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Current understanding of post-allo-HSCT AIHA remains insufficient. This study aimed to elucidate the features and significant predictors of post-allo-HSCT AIHA to guide precise clinical management. Methods A retrospective nested case-control study was conducted at Peking University People's Hospital from 2013 to 2024. A total of 61 patients with post-allo-HSCT AIHA were enrolled. For each case, three AIHA-free allo-HSCT recipients were randomly matched by sex, age (± 3 years), and transplant timing (± 3 months). Treatment modalities and responses of AIHA patients were analyzed. Cox regression analyses were employed to identify risk factors for post-allo-HSCT AIHA, as well as predictors of AIHA relapse and patient mortality. Results The incidence of post-allo-HSCT AIHA was 0.72%. During follow-up, 14 (22.95%) AIHA patients died (mostly because of severe infection-related complications) and 6 (9.84%) experienced AIHA relapse. Multivariate analysis showed that an unrelated donor was an independent risk factor for post-allo-HSCT AIHA (Hazard Ratio HR 2.323, P = 0.027), whereas a history of acute graft-versus-host disease was a protective factor (HR 0.340, P = 0.001). Corticosteroids combined with rituximab significantly increased the likelihood of treatment response ( P = 0.003), with no significant adverse reactions or treatment-related mortality observed. We revealed that mononuclear cell count at allo-HSCT was correlated with AIHA relapse (HR 1.720, P = 0.011). Age (per 10-year increase, HR = 1.669, P = 0.005), lactate dehydrogenase (LDH) level (per 100-unit increase, HR = 1.178, P = 0.020), and C-reactive protein level (CRP, mg/L, HR = 1.018, P = 0.031) were associated with an increased risk of mortality. Conclusions This study provides novel insights into post-allo-HSCT AIHA. These findings highlight key prognostic markers, guiding risk stratification and the management of AIHA after allo-HSCT.