The Late Effects of Hematopoietic Stem Cell Transplants in Pediatric Patients: A 25-Year Review

Abstract Context A rare, large, single-center study covering all long-term health outcomes of pediatric allogeneic hemopoietic stem cell transplant (HSCT) survivors, to provide comprehensive local data and identify gaps and future directions for improved care. Objective To document endocrine sequelae and other late effects of all HSCT recipients. Design Retrospective review. Setting Royal Children's Hospital Melbourne. Patients 384 children and adolescents received HSCT; 228 formed the study cohort; 212 were alive at commencement of data accrual. Intervention None. Main Outcome Measures Incidence of endocrinopathies; fertility, growth, bone and metabolic status; subsequent malignant neoplasms (SMNs). Results Gonadotoxicity was more common in females (P < .001). Total body irradiation (TBI) conditioning was more toxic than chemotherapy alone. All females receiving TBI or higher cyclophosphamide equivalent doses developed premature ovarian insufficiency. In males, impaired spermatogenesis +/- testicular endocrine dysfunction was associated with increasing testicular radiation exposure. Preservation of gonadal function was associated with younger age at HSCT. Of sexually active females, 22% reported spontaneous pregnancies. Short stature was common, with GH axis disruption in 30% of these. Of patients exposed to thyroid radiation, 51% developed nodules; 30% were malignant. Metabolic disturbances included hypertension and dyslipidemias, with both excess and underweight reported. Fragility fractures occurred in 6% and avascular necrosis in 6%. Thirteen percent developed SMNs, with the risk continuing to rise throughout follow-up. Conclusion We confirm gonadal dysfunction, multiple endocrine and metabolic abnormalities, thyroid cancer, and SMNs as common sequelae of HSCT and identify gaps in management—particularly the need for informed fertility counseling and pretreatment fertility preservation, evaluation, and management of bone health—and underline the need for early lifestyle modification, long-term surveillance, and prospective planned studies aimed at reducing complication risk.