Treosulfan-based vs. busulfan-based conditioning for hematopoietic stem cell transplantation: A systematic review and meta-analysis.

Abstract Introduction Stem cell transplantation (SCT) continues to be a conventional treatment for many malignant and non-malignant hematological disorders in individuals of all ages. The safety and efficacy of SCT are strongly influenced by the pre-transplant conditioning regimen. While Busulfan-based regimens are widely used, Treosulfan is gaining recognition for its potentially improved safety profile and comparable efficacy. With increased clinical adoption and available randomized controlled trials (RCTs) comparing these regimens, we conducted a meta-analysis to assess the safety and efficacy of Treosulfan-based versus Busulfan-based conditioning. Methods RCTs assessing SCT in individuals of all ages were included. A comprehensive search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov identified 96 records; 12 duplicates were removed, 84 were screened, and 9 trials met inclusion criteria. Outcomes included were graft-versus-host disease (GVHD) incidence, toxicity, treatment-related mortality (TRM), non-relapse mortality (NRM), event-free survival (EFS), overall survival (OS), relapse incidence (RI), and engraftment. Pooled analysis was conducted using Review Manager (RevMan 5.4) with a random-effects model. Results were expressed as risk ratios (RR) or mean differences with 95% confidence intervals (CIs). Statistical significance was set at p < 0.05, and heterogeneity among studies was assessed using the I² statistic. Sensitivity analysis was conducted to assess the robustness of findings and identify potential sources of heterogeneity; notably, statistical significance for most outcomes emerged after conducting these analyses. Ethical approval was not required as only published data were analyzed. Results A total of 6,350 patients across nine studies were included (1,688 in Treosulfan-based regimen and 4,662 in Busulfan-based regimen). Treosulfan-based conditioning was associated with better OS (RR = 0.73, 95%CI: 0.57–0.93; I² = 37%, p = 0.02), reduced GVHD incidence (RR = 0.74, 95%CI: 0.57–0.97; p = 0.03), and more favorable EFS (RR = 0.84, 95%CI: 0.72–0.97; p = 0.03) Engraftment showed slight improved with busulfan-based regimen (RR = 0.98, 95%CI: 0.96- 1.00; p = 0.03). No substantial or significance differences were observed between regimens for toxicity (RR = 1.11, p = 0.72), TRM (RR = 0.84, p = 0.69), NRM (RR = 0.93, p = 0.84), or relapse incidence (RR = 1.47, p = 0.11). Conclusion Although most outcomes between Treosulfan- and Busulfan-based regimens were statistically comparable, Treosulfan demonstrated non-inferiority in toxicity, TRM, NRM, and relapse incidence, along with consistently favorable results in OS, EFS, GVHD, and engraftment. These findings, reinforced by sensitivity analysis, emphasize the robustness of the results and highlight Treosulfan's potential as a reliable conditioning agent for broader clinical application.