Efficacy and safety profile of busulfan plus low-dose melphalan (BUMEL) versus high-dose melphalan (MEL200) as a conditioning regimen for autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma patients: a systematic review and meta-analysis.

INTRODUCTION

The optimal conditioning regimen prior to autologous stem cell transplantation (Auto-HSCT) in multiple myeloma remains uncertain. We conducted a systematic review and meta-analysis to compare the efficacy and safety of busulfan-melphalan (BUMEL) versus high-dose melphalan (HDMEL) conditioning.

METHODS

A systematic literature search of PubMed, Embase, and the Cochrane Library was performed to from inception to 15 April 2025 to identify comparative studies evaluating BUMEL and HDMEL conditioning prior to Auto-HSCT. Eligible studies reported efficacy and/or safety outcomes. Risk of bias was assessed using standard methodological criteria. Pooled hazard ratios and odds ratios with 95% confidence intervals were calculated using random-effects models.

RESULTS

Eleven studies comprising transplant-eligible patients with multiple myeloma were included. BUMEL conditioning was associated with improved progression-free survival compared with HDMEL, favoring BUMEL (HR: 0.83, 95% CI: 0.76-0.89, p < 0.00001), while no definitive overall survival benefit was observed HR: 1.10, 95% CI: 1.00-1.21, p = 0.05). BUMEL was associated with higher rates of mucositis, infections, and hepatic toxicity.

CONCLUSIONS

BUMEL conditioning offers improved disease control at the cost of increased toxicity, without a clear overall survival advantage. These findings support individualized conditioning selection, particularly in settings where upfront ASCT remains standard practice.

REGISTRATION: This protocol was registered on PROSPERO with an ID of CRD420261292372.