ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab. 2025 Jan 21;110(2):e347-e362. PMID: 38534046. doi: 10.1210/clinem/dgae196. [email protected]

Brief summary: This single-center, retrospective study analysed long-term health outcomes of 228 5-year survivors of pediatric allogeneic hematopoietic stem cell transplant (HSCT), treated between 1985 and 2011.

Gonadotoxicity was more common in females and in those who received total body irradiation (TBI)-based conditioning. All 24 women who received 12 Gy TBI developed premature ovarian insufficiency (POI), compared to 17/28 conditioned with busulfan/cyclophosphamide (BuCy). 32 of 33 men exposed to TBI or testicular irradiation exhibited impaired spermatogenesis. All 5 males who received TBI had azoospermia vs 3/6 conditioned with chemotherapy. Preservation of gonadal function was associated with younger age at HSCT. Spontaneous pregnancies were reported by 8 of 37 sexually active females, resulting in 10 live births; 3 had received TBI, and 5 had a prior POI diagnosis 5–16 years before conception. Short stature was common, with GH axis disruption documented in 30% of patients. 84 of 94 patients exposed to thyroid radiation had ultrasound data available; 51% developed nodules (30% malignant) after a median of 12 years from irradiation and 26% developed hypothyroidism. Diabetes or prediabetes was diagnosed in 7% of patients; lipids (available in 116/228 patients) were abnormal in 50% of cases. Among the 183 patients with available BMI data, 20% were obese, 9% overweight, and 10% underweight. Hypertension was found in 22 of 109 patients, with 10 receiving treatment. Vitamin D status was available in 113 of 228 patients and was abnormal in 45 patients. 17 HSCT survivors had died, primarily due to subsequent malignant neoplasms.

Comment: Long-term follow-up data from this large Australian study confirm the well-known sequelae of HSCT and the detrimental effects of TBI. A limitation of the study is the lack of relevant data (including weight, BMI, blood pressure, lipids, hormones, vitamin D levels, and ultrasound) for a significant proportion of patients, due to its retrospective design. The finding of a significant percentage of transplanted women with spontaneous pregnancies after a diagnosis of POI, is surprising and likely due to a transient recovery of ovarian function. It would be desirable to provide all patients, at the end of cancer therapy, with a precise long-term follow-up schedule in accordance with current guidelines (e.g., COG guidelines¹). Providing treatment summaries and targeted, timely education to patients and families is critical to promoting patient and family engagement, improving adherence to follow-up, ensuring continuity of care during transitions, enabling early monitoring of complications, and reducing variability in follow-up between centers.

Reference: 1. Children’s Oncology Group. Long term follow-up guidelines for survivors of childhood, adolescent and young adult cancers. Version 5.0. 2018.