Abstract
Background: Treosulfan has emerged as a potentially less toxic alternative to busulfan in conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, comparative evidence remains varied and inconsistent.
Methods: We conducted a comprehensive meta-analysis of 12 studies (3 randomized controlled trials and 9 cohort studies) involving 7,649 adult patients undergoing allogeneic HSCT for MDS or AML. A systematic search of PubMed, Embase, Cochrane Library, and Scopus (May 2025) was performed. Primary outcomes included overall response rate, non-relapse mortality (NRM), and acute graft-versus-host disease (aGVHD). Secondary outcomes included chronic GVHD (cGVHD), donor chimerism, event-free survival (EFS), relapse, engraftment, infection, organ toxicity, and veno-occlusive disease (VOD). Data were pooled using a random-effects model.
Results: Treosulfan-based conditioning was associated with significantly higher overall response (RR: 1.24; 95% CI: 1.09–1.42; p = 0.0004) and lower NRM (RR: 0.65; 95% CI: 0.34–1.24; p < 0.00001). A non-significant trend toward reduced grade III–IV aGVHD was observed (RR: 0.68; p = 0.07). Treosulfan also yielded higher full donor chimerism at day +100 (RR: 1.10; p = 0.003). No significant differences were found in cGVHD, infection rates, disease recurrence, EFS, engraftment kinetics, or overall mortality. Sensitivity analyses confirmed the robustness of key outcomes despite moderate heterogeneity in some endpoints.
Conclusions: Treosulfan-based conditioning regimens offer favorable efficacy and safety compared to busulfan, with reduced NRM and improved donor chimerism without compromising engraftment or increasing GVHD or relapse risk. These findings support Treosulfan as a clinically effective and better-tolerated alternative, particularly for older or medically vulnerable transplant recipients.
Keywords: Treosulfan, Busulfan, Conditioning regimen, Hematopoietic stem cell transplantation, MDS, AML, Meta-analysis
