Abstract
Background Relapse remains the leading cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Hypomethylating agents (HMAs) such as azacitidine and decitabine are increasingly used as post-transplant maintenance, but the magnitude of benefit after the latest clinical reports is unclear.
Methods We searched MEDLINE, Embase, CENTRAL, Pubmed to 31 March 2025 for randomized or non-randomized controlled studies comparing HMA maintenance with observation/standard care after allo-HSCT for AML/MDS. Outcomes were pooled as risk ratios (RR) using a random-effects Mantel–Haenszel model. Analyses were performed in RevMan 5.4.
Results Fourteen comparative studies met inclusion criteria, comprising 3 randomized trials and 10 retrospective and 2 prospective studies, with a total of 1716 patients . HMA maintenance significantly improved overall survival (risk ratio [RR] = 1.38, 95% confidence interval [CI]: 1.19–1.60) and relapse-free survival (RR = 1.46, 95% CI: 1.31–1.62). The cumulative incidence of relapse was reduced by 31% (RR = 0.69, 95% CI: 0.50–0.95), and non-relapse mortality was reduced by 64% (RR = 0.36, 95% CI: 0.19–0.66). Importantly, HMA maintenance did not increase the risk of grade III–IV acute GVHD (RR = 0.86, 95% CI: 0.38–1.94) or chronic GVHD (RR = 0.94, 95% CI: 0.65–1.34)
Conclusions This updated meta-analysis demonstrates that HMA maintenance after allo-HSCT confers clinically meaningful gains in overall and relapse-free survival, driven by both reduced relapse and lower non-relapse mortality, without increasing severe acute or chronic GVHD. These data support integrating HMAs into post-transplant protocols for high-risk AML/MDS.
