Outcomes for acute myeloid leukemia have improved significantly in the last decade with the approval of novel therapeutics targeting diverse vulnerabilities of leukemic cells, expanded access to stem cell transplantation, and improved safety of transplantation. While attainment of initial remission is now an expected outcome in most AML patients receiving intensive or non-intensive induction regimens, maintaining long-term remission and decreasing the risk of relapse remain critical challenges. Maintenance approaches employing assorted agents have yielded variable success and only recently have been integrated to the standard of care. We present four commonly encountered clinical scenarios that highlight challenges facing physicians as they care for AML patients in remission and contemplate using post-remission maintenance. Using published studies and emerging clinical data, we discuss our approach to maintenance treatment in AML, emphasizing that selection of a specific strategy is an individualized decision based on leukemia biology and risk stratification, presence of targetable mutations, initial treatment approach, performance status, and feasibility of allogeneic stem cell transplantation.

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