Background: Conditioning regimen selection significantly impacts the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. However, comparative evidence between Busulfan–Fludarabine and Busulfan–Cyclophosphamide remains inconclusive. Objectives: To compare the efficacy and safety of Busulfan–Fludarabine versus Busulfan–Cyclophosphamide as conditioning regimens prior to HSCT. Design: Systematic review and meta-analysis conducted in accordance with PRISMA 2020 guidelines. Data sources and methods: MEDLINE, CENTRAL, and Embase were searched through October 2024. Eligible studies included randomized controlled trials and cohort studies comparing Busulfan–Fludarabine and Busulfan–Cyclophosphamide in HSCT recipients. Primary outcomes included overall survival and acute graft-versus-host disease (GVHD). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Risk of bias was assessed using RoB 2.0 and the Newcastle–Ottawa Scale. Results: Eighteen studies (6 randomized controlled trials, 12 cohorts) comprising 2888 patients (1539 received Busulfan–Fludarabine, 1349 received Busulfan–Cyclophosphamide) were included. Busulfan–Fludarabine showed higher 1-year overall survival (RR 1.13, 95% CI: 1.01–1.26), but no significant difference at 2 or 5 years. Grade III–IV acute GVHD was significantly lower with Busulfan–Cyclophosphamide (RR 0.45, 95% CI: 0.21–0.98). Busulfan–Fludarabine resulted in lower 5-year non-relapse mortality (RR 0.63, 95% CI: 0.48–0.83), and significantly reduced pulmonary and gastrointestinal toxicities. Event-free survival favored Busulfan–Fludarabine at 2 and 5 years. No significant differences were found for relapse-related mortality, chronic GVHD, cytomegalovirus infection, or total mortality. Meta-regression identified conditioning regimen and graft source as contributors to 1-year survival variability. Conclusion: Busulfan–Fludarabine offers early survival and toxicity advantages, while Busulfan–Cyclophosphamide may reduce severe acute GVHD. Conditioning regimen selection should consider patient-specific factors. Further prospective trials are needed to guide clinical decisions. Trial registration: PROSPERO ID: CRD42025630836.
Ali et al. (Thu,) studied this question.