Outcomes of fludarabine-melphalan versus fludarabine-busulfan reduced-intensity conditioning regimens for allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies: A systematic review and meta-analysis.

[BACKGROUND] Fludarabine with melphalan (FM) or busulfan (FB) is among the most widely used reduced-intensity conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The authors conducted a systematic review and meta-analysis comparing these regimens in adult patients with hematologic malignancies.

[METHODS] A comprehensive search of Ovid MEDLINE, Embase, and the Cochrane Library from inception through July 22, 2025, identified 17 eligible studies involving 10,396 patients. Pooled analyses were performed using a random-effects model, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated.

[RESULTS] In the overall analysis, FM was associated with improved progression-free survival (PFS) (HR, 0.90; 95% CI, 0.82-0.98), driven by lower relapse rates (HR, 0.69; 95% CI, 0.62-0.78) but increased treatment-related mortality (TRM) (HR, 1.44; 95% CI, 1.10-1.89). There were no significant differences in overall survival (OS), grade 3-4 acute graft-versus-host disease (GVHD), or chronic GVHD. In subgroup analyses, FM significantly improved OS and PFS, primarily driven by a significant reduction in relapse risk in acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) and elderly patients aged ≥60 years without significant differences in TRM. In contrast, for lymphoma patients, FM was associated with worse OS and higher TRM compared with FB, and no advantage in PFS, but significantly lower relapse.

[CONCLUSIONS] These findings suggest that FM may be a preferred reduced-intensity regimen for AML/MDS and elderly patients, whereas lower intensity regimens may be needed for lymphoma to reduce TRM and optimize long-term survival after allo-HSCT.