Osteonecrosis as a Complication of Treating Acute Lymphoblastic Leukemia in Children: A Report From the Children’s Cancer Group

Abstract

PURPOSE: To determine the incidence, risk factors, and morbidity for osteonecrosis (ON) in children with acute lymphoblastic leukemia (ALL) treated with intensive chemotherapy including multiple, prolonged courses of corticosteroid. PATIENTS AND METHODS: The occurrence of symptomatic ON was investigated retrospectively in 1,409 children ages 1 to 20 years old receiving therapy for high-risk ALL on Children’s Cancer Group (CCG) protocol CCG-1882. RESULTS: ON was diagnosed in 111 patients (9.3% ± 0.9%, 3-year life-table incidence). The incidence was higher for older children (≥ 10 years: 14.2% ± 1.3% v < 10 years: 0.9% ± 0.4%; P < .0001), especially females 10 to 15 years old and males 16 to 20 years old (19.2% ± 2.3% and 20.7% ± 4.7%, respectively). In patients 10 to 20 years old, the incidence of ON was higher for females versus males (17.4% ± 2.1% v 11.7% ± 1.6%, respectively; P = .03) and for patients randomized to receive two 21-day dexamethasone courses versus one course (23.2% ± 4.8% v 16.4% ± 4.3%, respectively; P = .27). Among ethnic groups, whites had the highest incidence and blacks the lowest, with other groups intermediate (16.7% ± 1.4% v 3.3% ± 2.3% v 6.7% ± 2.2%, respectively; P = .003). There was no difference in event-free survival in patients with or without ON. ON was diagnosed within 3 years of starting ALL therapy in all but one patient, involved weight-bearing joint(s) in 94% of patients, and was multifocal in 74% of patients. Symptoms of pain and/or immobility were chronic in 84% of patients, with 24% having undergone an orthopedic procedure and an additional 15% considered candidates for surgery in the future. CONCLUSION: Children ages 10 to 20 years who receive intensive ALL therapy, including multiple courses of corticosteroid, are at significant risk for developing ON.