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Relapse remains a major cause of treatment failure for acute myeloid leukemia (AML) patients treated with allogeneic hematopoietic stem cell transplantation (allo-HCT). Most patients that recur will perish due to low treatment efficacy, toxicity, or frailty issues. This review summarizes recent developments in clinical research and therapeutic applications for prevention and treatment of this complication of transplantation.Several groups have demonstrated that monitoring minimal residual disease (MRD) after allo-HCT is feasible and is predictive of impending hematologic recurrence. The introduction of novel antileukemia agents in the preparative regimen, maintenance of remission treatment posttransplant, and early MRD-based therapeutic interventions all have the potential to improve outcomes.Innovative basic and clinical investigation is urgently needed to improve treatment and prevention of AML recurrence after allogeneic transplantation.