Maintenance Therapy After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia: Still an Open Question?

Disease relapse remains the leading cause of treatment failure in patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). This narrative review, searched from Pubmed, from 2015 to 2026, critically synthesizes the available evidence on post-transplant maintenance strategies, which have evolved over the past three decades from conventional chemotherapy to molecularly targeted agents and interventions aimed at modulating antileukemic immunity. Particular attention is given to the biological rationale, efficacy, safety, and clinical applicability of these approaches, as well as to the substantial heterogeneity in study design, patient selection, and treatment initiation and duration. The available evidence indicates that the potential benefit of maintenance is unlikely to be uniform across all recipients and should be interpreted in relation to AML molecular features, baseline relapse risk, prior treatment exposure, measurable residual disease status, expected toxicity, and the patient’s overall clinical condition. Although selected strategies may prolong remission and improve survival, the optimal agent, timing, duration, and target population remain incompletely defined. Current evidence therefore supports a risk-adapted and molecularly informed approach, while underscoring the need for adequately powered prospective studies using standardized endpoints and incorporating quality-of-life outcomes.