Maintenance therapy after allogeneic stem cell transplantation for relapse prevention in myeloid malignancies

Relapse remains the leading cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and outcomes after relapse are poor. This review summarizes and critically appraises current evidence for post-HCT maintenance therapy aimed at relapse prevention.

Patient selection increasingly rests on disease risk and the presence of a targetable mutation. FLT3 inhibitors carry the strongest evidence: randomized trials support sorafenib and gilteritinib in FLT3 internal tandem duplication (FLT3-ITD) AML, and the MORPHO trial showed that measurable residual disease (MRD) status identifies patients most likely to benefit. Isocitrate dehydrogenase (IDH) inhibitors and menin inhibitors are promising but lack randomized data. For patients without actionable mutations, hypomethylating agent maintenance has produced inconsistent results, and the evidence more strongly supports MRD-triggered preemptive therapy.

Post-HCT maintenance has shifted from broadly applied, poorly tolerated regimens toward targeted, MRD-guided strategies. Important uncertainties remain regarding optimal patient selection, agent choice, timing, and duration. Adequately powered, HCT-specific randomized trials with standardized MRD endpoints are the principal unmet need.