Treosulfan conditioning in hematopoietic stem cell transplantation: A safer approach for hematologic disorders

Abstract:

Treosulfan is a water-soluble bifunctional alkylating prodrug that has emerged as an effective conditioning agent for hematopoietic stem cell transplantation (HSCT) in both malignant and nonmalignant hematologic disorders. Compared with conventional busulfan- or total body irradiation-based regimens, treosulfan offers a more favorable toxicity profile while maintaining adequate myeloablative and immunosuppressive efficacy. Clinical evidence supports its ability to achieve reliable engraftment and immune reconstitution across diverse patient populations. Pharmacokinetic studies demonstrate largely predictable, dose-dependent exposure, although inter-patient variability – particularly in pediatric recipients – suggests a potential role for therapeutic drug monitoring to optimize dosing. Importantly, treosulfan-based conditioning is associated with reduced acute and long-term toxicities, including a lower risk of gonadal dysfunction, making it especially attractive for pediatric and adolescent patients in whom fertility preservation is a major concern. This review synthesizes current evidence on the pharmacology, clinical applications, safety profile, and pharmacokinetics of treosulfan, highlighting its growing role in individualized, less toxic HSCT conditioning strategies and outlining key challenges and future research directions.