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

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.