Busulfan and cyclophosphamide vs busulfan and fludarabine for myeloablation in the patients of acute myeloid leukaemia/ myelodysplastic syndrome undergoing stem cell transplant: A systematic review and meta-analysis.

Abstract

e18545 Background: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are key indications for hematopoietic stem cell transplantation (HSCT). While the Busulfan-Cyclophosphamide (BuCy) regimen has been a standard, it carries high risks of hepatic veno-occlusive disease (HVOD) and non-relapse mortality (NRM), especially in older patients. Busulfan-Fludarabine (BuFlu) has emerged as a less toxic alternative. This meta-analysis compares the efficacy and safety of BuCy and BuFlu in AML/MDS patients undergoing HSCT to identify the optimal conditioning regimen. Methods: A systematic review of PubMed, Cochrane, Embase, and ClinicalTrials.gov (search date: January 2, 2025) identified studies evaluating 1- and 5-year Overall Survival (OS), Progression-Free Survival (PFS), acute/chronic Graft-versus-Host Disease (aGVHD/cGVHD), and Non-Relapse Mortality (NRM). Random-effects meta-analysis using the Mantel-Haenszel method synthesized data via RevMan 5.4. Results: This meta-analysis included fourteen studies involving 2448 patients (BuCy: 1151, BuFlu: 1297). BuCy demonstrated superior 1-year OS (OR = 0.70, 95% CI: 0.51–0.96, p = 0.03) compared to BuFlu, with moderate heterogeneity (I² = 54%, p = 0.01). No significant difference was observed in 5-year OS (OR = 1.12, 95% CI: 0.66–1.91, p = 0.67). A non-significant trend favoring BuFlu was noted for 1-year PFS (OR = 0.78, 95% CI: 0.55–1.11, p = 0.17, I² = 58%), with no differences at 5 years (OR = 0.86, 95% CI: 0.55–1.34, p = 0.49, I² = 74%). Incidences of aGVHD (OR = 1.35, 95% CI: 0.78–2.33, p = 0.29, I² = 82%) and cGVHD (OR = 0.90, 95% CI: 0.57–1.42, p = 0.64, I² = 75%) were comparable between regimens. BuFlu, however, was associated with significantly higher 1-year NRM (OR = 1.99, 95% CI: 1.41–2.82, p < 0.0001, I² = 33%), though no significant differences were observed at 5 years (OR = 1.08, 95% CI: 0.55–2.11, p = 0.83, I² = 79%). Conclusions: BuCy and BuFlu regimens offer comparable long-term efficacy, but BuCy provides better early survival and lower 1-year NRM, making it a safer option, especially for high-risk patients. Further studies are needed to confirm these findings and refine HSCT conditioning strategies.