Transplant Outcomes in Acute Myeloid Leukemia

Transplant-eligible adults with acute myeloid leukemia (AML) and higher-risk molecular subtypes typically undergo allogeneic hematopoietic cell transplantation (allo HCT) to deepen response and improve cure rates. To determine the impact of residual peripheral blood leukemic cell DNA on post-transplant outcomes, investigators conducted a multicenter retrospective analysis of patients who underwent allo HCT during first complete remission following induction chemotherapy.

Eligible patients had mutations at the time of AML diagnosis (FLT3, NPM1, IDH1, IDH2, and/or KIT) as well as a remission blood sample obtained within 100 days of the allo HCT. Transplants were performed at least 3 years before the study analysis. DNA analysis for measurable residual disease (MRD) was assessed by next-generation sequencing, with a cut-off level of 0.01% for the variant allele fraction to determine MRD-positive versus MRD-negative status.

Using the database of the Center for International Blood and Marrow Transplant Research, the investigators studied a discovery cohort of 454 patients and a validation cohort of 621 patients. Among 451 patients in the validation cohort with NPM1 mutations, FLT-ITD mutations, or both at the time of diagnosis, the rate of relapse by 3 years was significantly higher for those with pretransplant detectable MRD above the cut-off level compared with below it (68% vs. 21%; P<.001), which was also reflected in poorer overall survival (39% vs. 63%; P<.001).