Venetoclax in combination with azacitidine (VEN-AZA) has become the standard of care for acute myeloid leukemia (AML) patients who are elderly or unfit to receive intense chemotherapy. However, the efficacy and safety of this regimen in AML patients who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) still needs more exploration.

We conducted a retrospective analysis of the data of 9 patients with relapsed AML after allo-HSCT treated with VEN-AZA from April 2021 to May 2023 at our center. Of these, 6 had molecular relapses (including persistent positive molecular markers) and 3 had hematologic relapses.

The objective response rate was 55.6 % for all patients and 66.7 % and 33.3 % for patients with molecular and hematologic relapses, respectively ( P = 0.524). Median overall survival was 201 days for the entire cohort, compared to 258 days and 68 days in the respective subgroups ( P = 0.023). Molecular markers converted to negative in three patients with CBFβ::MYH11 and one with NPM1 mutation, seem to indicate a favorable response to VEN-AZA. This regimen was well tolerated, but hematologic toxicity and infections were common. Additionally, acute graft-versus-host disease (aGVHD) occurred in three patients, one of whom presented with a severe, multiphasic course.

The early use of VEN-AZA appears to be effective and well tolerated in AML patients with molecular relapse after allo-HSCT, particularly in those carrying CBFβ::MYH11 fusion gene or NPM1 mutation.