Late Endocrine and Organ Toxicities After Treosulfan-Based Conditioning in Pediatric Hematopoietic Cell Transplantation: A Systematic Review.

Treosulfan is an alkylating agent indicated as a conditioning agent for allogeneic hematopoietic cell transplantation (HCT), with an established favorable acute toxicity profile; however, its long-term sequelae remain incompletely characterized. This review aims to characterize the late effects following treosulfan-based conditioning in pediatric HCT and to identify critical gaps in published evidence. This systematic review was conducted in accordance with PRISMA guidelines and prospectively registered with PROSPERO (CRD420261345072). PubMed, Embase, and the Cochrane Library were searched from inception through April 28, 2026 for studies reporting late effects in patients aged ≤ 40 years at the time of HCT who received treosulfan-based conditioning. Risk of bias was assessed using the Newcastle-Ottawa Scale. Sixteen retrospective studies met inclusion criteria. Three studies evaluated sex hormone replacement therapy, and none of the patients receiving treosulfan required it. Treosulfan use was associated with significantly less gonadal toxicity compared to busulfan in several cohorts. Non-gonadal endocrine or non-endocrine late effects were reported mostly in single cohorts with no significant differences compared to busulfan. In conclusion, treosulfan-based conditioning appears to have a meaningfully lower risk to gonadal dysfunction compared to busulfan, most prominently in patients with nonmalignant diagnoses and in females. No significant differences were observed for non-gonadal late effects, albeit data remain limited.