Single-center retrospective analysis of venetoclax-based triple-drug combination therapy for relapsed Acute Myeloid Leukemia  post allogeneic hematopoietic stem cell transplantation.

Abstract Objective: To evaluate the efficacy and safety of venetoclax (VEN), cytarabine, and azacitidine (AZA) combination therapy in relapsed acute myeloid leukemia (AML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: This study included AML patients who underwent allo-HSCT and experienced relapse between January 2020 and January 2025 at our center. All received combined VEN, cytarabine, and AZA for relapse. Clinical characteristics, laboratory data, treatment regimens, and outcomes were retrospectively analyzed. Results: A total of 30 patients (14 females, 16 males) who received haploidentical allo-HSCT were included. Genetic abnormalities included MLL rearrangement ((n=5)), CBFβ-MYH11 fusion ((n=5)), AML1-ETO positivity ((n=2)), and NUP98 rearrangement ((n=2)). Median time from transplant to relapse was 6.2 months (range: 2.3–47). Relapse types included molecular relapse (measurable residual disease [MRD]-positive, (n=14)) and morphological relapse ((n=16)). Median follow-up was 20 months (range: 4–46). After one treatment cycle: MRD-positive subgroup (n=14): 5 (35.7%) achieved MRD clearance; 7 (50.0%) showed reduced fusion gene levels; 2 (14.3%) progressed. Morphological relapse subgroup (n=16): 9 (56.3%) achieved complete remission (CR), including 6 (37.5%) with MRD-negative deep remission and 3 (18.8%) with MRD-positive remission; 1 (6.25%) achieved partial remission (PR); 5 (31.3%) progressed; 1 (6.25%) died before evaluation. Overall response rate (ORR): 73.3%(8/30), with MRD-negative CR rate of 36.7%(10/30). After two cycles: ORR 66.7%; MRD-negative CR rate: 57.1%. Adverse events: Hematologic toxicity: Neutropenia median duration 18 days (range: 11–34). Grading: grade 2 ((n=1)), grade 3 ((n=9)), grade 4 ((n=11)). Thrombocytopenia median duration 19 days (range: 14–35). Grading: grade 3 ((n=7)), grade 4 ((n=14)). Infections: 14 patients developed pulmonary infections during neutropenia. Two fatal cases occurred: one due to Pneumocystis jirovecii pneumonia and one due to bloodstream Rhizopus infection. Conclusion: The VEN-cytarabine-AZA triple-drug regimen is an effective option for relapsed AML after allo-HSCT. However, prolonged neutropenia and thrombocytopenia necessitate vigilant monitoring for severe infections.