Efficacy and safety of busulfan-fludarabine versus busulfan-cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplant in hematologic malignancy patients: A meta-analysis of randomized controlled trials and observational s

e18546 Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a life-saving treatment for hematologic malignancies but comes with risks like graft-versus-host disease (GVHD), infections, and organ damage. Conditioning regimens are crucial in influencing outcomes. While Busulfan-Cyclophosphamide (BuCy) is linked to higher toxicity, Busulfan-Fludarabine (BuFlu) carries a greater risk of graft failure. This meta-analysis compares these regimens to identify the optimal approach for enhancing survival and minimizing complications. Methods: A systematic search of PubMed, Embase, and Web of Science from their inception to October 2024 identified studies comparing BuFlu and BuCy in allogeneic HSCT. Meta-analyses used the random-effects model in RevMan (v5.4.1), with results reported as relative risks (RR) and 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Results: This meta-analysis included six randomized controlled trials and twelve observational cohort studies with a total of 2,888 patients (BuFlu: n=1,539; BuCy: n=1,349). No significant differences were observed between BuFlu and BuCy for 5-year overall survival (RR: 1.08, 95% CI: 0.99–1.17, p=0.10), relapse incidence at 5 years (RR: 1.17, 95% CI: 0.90–1.52, p=0.24), or relapse-related mortality (RR: 0.93, 95% CI: 0.76–1.14, p=0.48). However, BuCy was associated with a significantly higher 5-year event-free survival (RR: 1.11, 95% CI: 1.01–1.24, p=0.04). For adverse events, BuCy was linked to a lower incidence of Grade III-IV acute GVHD (RR: 0.45, 95% CI: 0.21–0.98, p=0.04), while BuFlu showed a significantly lower rate of pulmonary toxicity (RR: 0.42, 95% CI: 0.18–0.97, p=0.04). No significant differences were observed for Grade II-IV acute GVHD (RR: 0.86, 95% CI: 0.55–1.34, p=0.51), Grade I acute GVHD (RR: 1.50, 95% CI: 0.80–2.79, p=0.20), limited chronic GVHD (RR: 0.76, 95% CI: 0.44–1.32, p=0.33), extensive chronic GVHD (RR: 0.92, 95% CI: 0.66–1.29, p=0.63), cytomegalovirus infection (RR: 0.93, 95% CI: 0.62–1.37, p=0.70), or liver toxicity (RR: 0.73, 95% CI: 0.45–1.18, p=0.20). Conclusions: This meta-analysis highlights the distinct benefits and limitations of BuFlu and BuCy conditioning regimens in allogeneic HSCT. While BuCy demonstrated higher 5-year event-free survival and lower rates of Grade III-IV aGVHD, BuFlu was associated with significantly lower pulmonary toxicity. These findings suggest that the choice of conditioning regimen should be tailored to individual patient profiles, balancing efficacy and toxicity to optimize outcomes. Further research is warranted to confirm these results and guide personalized conditioning strategies.