Post-transplant cyclophosphamide as graft-versus-host disease prophylaxis for matched related donor hematopoietic stem cell transplantation in acute leukemia: a systematic review and meta-analysis

Abstract

Although allogeneic hematopoietic stem cell transplantation (HSCT) offers curative potential for acute leukemia, graft-versus-host disease (GVHD) remains a major obstacle to optimal clinical outcomes. Evidence for post-transplant cyclophosphamide (PTCy) in the matched related donor (MRD) setting is limited, complicating its integration into standard practice. We systematically reviewed studies published up to April 2025 in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library, including patients with acute leukemia undergoing MRD-HSCT with PTCy-based GVHD prophylaxis. Twenty-one studies with 10860 patients were analyzed. PTCy significantly reduced acute GVHD grades II–IV (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.35–0.86) and chronic GVHD (OR: 0.47, 95% CI: 0.37–0.60) compared with calcineurin inhibitor-based regimens, and improved GVHD-free/relapse-free survival (OR: 2.29, 95% CI: 1.42–3.67). DFS was similar between groups (OR: 1.05, 0.75, 1.49). Non-significant trends suggested lower non-relapse mortality (OR: 0.71, 95% CI: 0.51–1.01) and improved overall survival (OR: 1.23, 95% CI: 0.94–1.62). Adverse events included delayed engraftment, cytomegalovirus reactivation (29%), and hemorrhagic cystitis (20%). Overall, PTCy appears to reduce GVHD without increasing relapse or mortality, supporting its use in MRD transplantation protocols. Further randomized trials are warranted to refine dosing and optimize prophylaxis strategies.