Azacitidine plus venetoclax as post-transplant maintenance therapy in high-risk myeloid malignancies: a propensity score-matched analysis

Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation(allo-HSCT) for high-risk myeloid malignancies. This single center, retrospective study enrolled patients with high-risk acute myeloid leukemia or myelodysplastic syndromes who received allo-HSCT from January 1, 2022 to December 31, 2024. Post-transplant maintenance therapy consisted of azacitidine (32 mg/m²/day, day 1-5) plus venetoclax (400 mg/day, day 1-7), starting from the 60th day posttransplant and repeated every 28 days until up to 1-year posttransplant. Outcomes were compared with a contemporaneous control group constructed via propensity score matching (azacitidine-venetoclax, n = 35; control, n = 59). After a median follow-up of 22.5 months, the 1-year disease-free survival was 88.6% (95% CI, 78.6%-99.8%), the 1-year cumulative incidence of relapse was 5.7% (95% CI, 0%-13.5%). The azacitidine-venetoclax group demonstrated significantly superior 1-year overall survival compared to control (P = 0.037). Win ratio analysis further confirmed a significant overall clinical benefit (P < 0.001). Subgroup analysis revealed a pronounced overall survival benefit for MRD-positive patients (HR, 0.288; P = 0.037). The safety profile was manageable, no significant increase in the incidences of EBV and CMV infection or graft-versus-host disease. Immune reconstitution analysis showed delayed B-cell recovery but preserved T-cell and NK-cell recovery.