Journal of clinical oncology, 2011-11-01, Vol.29 (31), p.4143-4150
PURPOSE: We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Osteonecrosis was defined by development of symptoms (National Cancer Institute grade 2 to 4) during treatment or within 1 year after treatment discontinuation, confirmed by magnetic resonance imaging. We evaluated risk factors for osteonecrosis using logistic multivariate regression. To describe outcome, we reviewed clinical and radiologic information after antileukemic treatment 1 year or more after osteonecrosis diagnosis. RESULTS: Cumulative incidence of osteonecrosis at 3 years was 6.1%. After adjustment for treatment center, logistic multivariate regression identified age (odds ratio [OR], 1.47; P 〈 .01) and female sex (OR, 2.23; P = .04) as independent risk factors. Median age at diagnosis of ALL in patients with osteonecrosis was 13.5 years, compared with 4.7 years in those without. In 21 (55%) of 38 patients with osteonecrosis, chemotherapy was adjusted. Seven patients (18%) underwent surgery: five joint-preserving procedures and two total-hip arthroplasties. Clinical follow-up of 35 patients was evaluated; median follow-up was 4.9 years. In 14 patients (40%), symptoms completely resolved; 14 (40%) had symptoms interfering with function but not with activities of daily living (ADLs; grade 2); seven (20%) had symptoms interfering with ADLs (grade 3). In 24 patients, radiologic follow-up was available; in six (25%), lesions improved/disappeared; in 13 (54%), lesions remained stable; five (21%) had progressive lesions. CONCLUSION: Six percent of pediatric patients with ALL developed symptomatic osteonecrosis during or shortly after treatment. Older age and female sex were risk factors. After a median follow-up of 5 years, 60% of patients had persistent symptoms.
Adolescent ; Age Factors ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Biological and medical sciences ; Child ; Child, Preschool ; Dexamethasone - administration & dosage ; Dexamethasone - adverse effects ; Diseases of the osteoarticular system ; Female ; Follow-Up Studies ; Humans ; Incidence ; Kaplan-Meier Estimate ; Logistic Models ; Magnetic Resonance Imaging ; Male ; Medical sciences ; Multivariate Analysis ; Netherlands - epidemiology ; Odds Ratio ; Osteonecrosis - chemically induced ; Osteonecrosis - diagnosis ; Osteonecrosis - diagnostic imaging ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Prevalence ; Proportional Hazards Models ; Prospective Studies ; Radiography ; Risk Assessment ; Risk Factors ; Sex Factors ; Time Factors ; Treatment Failure ; Treatment Outcome ; Tumors ; Vascular bone diseases
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