The late effects of haematopoietic stem cell transplants in paediatric patients: a 25 year review.

Abstract

A rare, large single centre study covering all long-term health outcomes of paediatric allogeneic HSCT survivors, to provide comprehensive local data, and identify gaps and future directions for improved care. To document endocrine sequelae and other late effects of all HSCT recipients. Retrospective review. Royal Children's Hospital Melbourne. 384 children and adolescents received HSCT. 228 formed the study cohort; 212 were alive at commencement of data accrual. None. Incidence of endocrinopathies; fertility, growth, bone and metabolic status; subsequent malignant neoplasms (SMNs). Gonadotoxicity was more common in females (p<0.001). Total body irradiation (TBI) conditioning was more toxic than chemotherapy alone. All females receiving TBI or higher cyclophosphamide equivalent doses (CED) developed premature ovarian insufficiency (POI) . 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 growth hormone axis disruption in 30% of these. Of patients exposed to thyroid radiation 51% developed nodules, 30% malignant. Metabolic disturbances included hypertension, dyslipidemias, with both excess and underweight reported. Fragility fractures occurred in 6%; avascular necrosis in 6%. 13% developed SMNs, risk continuing to rise throughout follow-up. 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 counselling and pretreatment fertility preservation, evaluation and management of bone health, and underline need for early lifestyle modification, long-term surveillance, and prospective planned studies aimed at reducing complication risk.