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

From the Michigan State University/Kalamazoo Center for Medical Studies, Kalamazoo, MI; Children’s Cancer Group, Los Angeles, CA; Dupont Hospital for Children, Jefferson Medical College, Wilmington, DE; and University of Chicago Medical Center, Chicago, IL.

Address reprint requests to Leonard A. Mattano, Jr, MD, Children’s Cancer Group, P.O. Box 60012, Arcadia, CA 91066-6012.

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.

Contributing Children’s Cancer Group investigators, institutions, and grant numbers are listed in the Appendix.

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