Allogeneic hematopoietic stem cell transplantation and pre-transplant strategies in patients with NPM1-mutated acute myeloid leukemia

Patients with acute myeloid leukemia (AML) and nucleophosmin 1 gene mutations (NPM1 mut ) show a favorable prognosis with chemotherapy (CT) in the absence of negative prognostic genetic abnormalities. Between 2008 and 2021 64 patients with NPM1 mut AML received alloHSCT because of additional adverse prognostic factors (1 st line), inadequate response to or relapse during or after CT (2 nd line). To expand the evidence in alloTX in NPM1 mut AML, clinical and molecular data were retrospectively analyzed with respect to pre-transplant strategies and outcome. Patients with minimal residual disease negative (MRD-) CR at transplant had better 2-y-PFS and 2-y-OS (77% and 88%) than patients with minimal residual disease positive (MRD+) CR (41% and 71%) or patients with active disease (AD) at transplant (20% and 52%). The 2 nd line patients with relapse after completing CT responded well to high dose cytarabine based salvage chemotherapy (salvage CT) in contrast to patients relapsing while still on CT (90% vs 20%, p=0.0170). 2-y-PFS and 2-y-OS was 86% in patients who achieved a 2 nd MRD- CR pre alloHSCT. Outcome in NPM1 mut AML depends on disease burden at alloHSCT. Time and type of relapse in relation to CT are predictive for response to salvage CT.