Endocrine Late Effects Following Allogeneic Hematopoietic Cell Transplant Using Treosulfan-Based Conditioning for Treatment of Non-Malignant Diseases: Contextual Comparison with NHANES Pediatric and Young Adult Data

Abstract

Treosulfan-based conditioning regimens have emerged as a reduced-toxicity alternative to conventional myeloablative conditioning for hematopoietic cell transplantation (HCT) in pediatric and young adult patients with non-malignant diseases (NMD). Despite growing use, the endocrine late effect profile of treosulfan-based conditioning remains poorly characterized. This retrospective cohort study describes the prevalence of endocrine late effects requiring therapy at last follow-up among 102 survivors of treosulfan-based HCT for NMD enrolled across two consecutive institutional clinical trials. A 4:1 frequency-matched general population comparator was drawn from the 2015–2016 National Health and Nutrition Examination Survey (NHANES). Endocrine late effects requiring pharmacotherapy were uncommon. Thyroid disease was the most prevalent at 6.3% compared to 2.3% in the NHANES comparator (PR 2.78, 95% CI 0.71–10.83), though this did not reach statistical significance. Notably, HCT survivors were significantly more likely to be underweight (11.0% vs. 3.6%; PR 3.08, 95% CI 1.42–6.66; p=0.008) and significantly less likely to have high BMI (6.0% vs. 23.9%; PR 0.25, 95% CI 0.11–0.56; p<0.001) compared to matched peers, potentially reflecting absence of TBI exposure and related to underlying non-malignant disease. These results provide an early characterization of endocrine late effects in this population and underscore the need for continued longitudinal follow-up as survivors age into adulthood.