How I Treat AML relapse after allogeneic HCT.

Allogeneic hematopoietic stem-cell transplantation (HCT) is one of the principal curative approaches in the treatment of acute myeloid leukemia (AML); however, relapse post-transplantation remains a catastrophic event with poor prognosis. The incidence of relapse has remained unchanged over the last three decades despite an evolving understanding of the immunobiology of the graft-versus leukemia effect and the immune escape mechanisms that lead to post-HCT relapse. The approach to post-transplant relapse is highly individualized and is dictated both by disease biology and genomics as well as the patient's clinical status at the time of relapse and the interval between relapse and transplantation. With the help of three illustrative cases, we discuss our approach to early, late, and incipient relapse. Current therapeutic strategies incorporate immunosuppression taper when feasible, a variety of targeted and non-targeted chemotherapeutic agents and consolidative cellular therapies including donor lymphocyte infusions or a second allogeneic transplant. We then summarize evolving frontiers in the treatment and prognostication of relapse including the critical role of measurable residual disease. Finally, we emphasize enrollment on clinical trials and thoughtful discussions regarding goals of care and supporting frail patients as universal principles that should be incorporated in approaches to treatment of AML relapse post-transplantation.