Introduction Autoimmune hemolytic anemia (AIHA) is a rare yet serious hematologic disorder, defined as hemolytic anemia characterized by the destruction of red blood cells (RBCs) mediated by autoantibodies targeting antigens on the RBC surface. As an infrequent complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), AIHA significantly complicates posttransplant patient management and increases the risk of adverse prognostic outcomes. Current therapies in this field lack robust clinical evidence for efficacy, and no studies have identified prognostic predictors of AIHA following allo-HSCT.

Methods A total of 61 AIHA patients who underwent allo-HSCT from 2013 to 2024 were identified. We performed a nested case‒control study to identify the risk factors for AIHA following allo-HSCT, and three controls were randomly selected for each case according to sex, age (±3 years), and time of transplant (±3 months). Clinical characteristics were compared between AIHA patients and matched controls. Binary Cox regression was performed to explore the risk factors for AIHA following allo-HSCT and predictors of relapse or mortality. Additionally, the treatment modalities and responses of AIHA patients were compared and analyzed.

Results The incidence of AIHA following allo-HSCT at Peking University People's Hospital from 2013 to 2024 was 0.72% (6.02/10000 person-years). Among the 61 patients identified as having post-allo-HSCT AIHA, 42 (68.9%) were males, and 19 (31.1%) were females. Fifty-eight (95.1%) patients were identified as having warm antibody-mediated AIHA, while the other 3 (4.9%) patients had cold agglutinin disease. The median age at allo-HSCT was 23 years (interquartile range [IQR]: 8-37 years), and the median time of AIHA onset was 195 days (IQR: 105–375 days) following allo-HSCT. Twelve (23.0%) AIHA patients died within the follow-up period, whereas 6 (9.8%) patients experienced AIHA relapse. Severe infection-related complications accounted for 10 (83.3%) deaths, and the remaining 2 deaths were attributed to hepatic failure and severe hemolysis, respectively.

There was no significant difference in overall survival between the AIHA and control groups (23.0% vs. 14.8%, p = 0.138). Univariate analysis revealed unrelated donors and cytomegalovirus infection following allo-HSCT as risk factors for post-allo-HSCT AIHA, whereas aGVHD was associated with reduced risk. Multivariate analysis revealed that an unrelated donor (HR 2.310, p = 0.028) was an independent risk factor for AIHA following allo-HSCT, whereas a history of aGVHD (HR 0.368, p = 0.002) was a protective factor.

Fifty-two (85.2%) patients achieved complete response (CR) or response (R) during the treatment course. The median time from AIHA onset to CR/R achievement was 21.5 days (IQR: 16–42 days). Prednisolone combined with Rituximab, as the first-line treatment regimen, has been found to increase the likelihood of patients with post-allo-HSCT AIHA achieving a CR/R (log rank p = 0.003); however, this treatment protocol did not improve overall survival. Furthermore, other currently recommended therapeutic interventions, including corticosteroids alone, plasma exchange, cyclosporine A, and mycophenolate mofetil have demonstrated no significant positive effects on treatment response or long-term survival. Additionally, no obvious adverse reactions were observed.

According to the prognostic analysis, the mononuclear cell count at allo-HSCT (HR 1.720, p = 0.011) was found to be an independent predictor of AIHA relapse. Univariate regression analysis revealed that age; lactate dehydrogenase (LDH), and C-reactive protein levels at AIHA onset; post-allo-HSCT viral infection; and history of acute kidney injury (AKI) before AIHA onset were potential risk factors for mortality. Multivariate regression analysis indicated that age (HR 1.067, p = 0.002), LDH level at AIHA onset (HR 1.002, p = 0.002), and AKI before AIHA onset (HR 8.811, p = 0.023) were independent risk factors for post-allo-HSCT AIHA mortality.

Conclusions This study enrolled the largest known cohort of patients with AIHA following allo-HSCT to date, reporting its incidence and clinical features. Further analyses identified risk factors and clinical outcomes and, for the first time, elucidated prognostic predictors of post-allo-HSCT AIHA. These findings innovatively highlight key prognostic markers, guiding risk stratification and the management of AIHA following allo-HSCT.

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2025
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