title: Prospective study on incidence, risk factors, and long-term outcome of osteonecrosis in pediatric acute lymphoblastic leukemia.
abstract: OBJECTIVE
  We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Erasmus MC-Sophia Children's Hospital, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands.
authors.forename: Mariël L
authors.initials: ML
authors.lastname: te Winkel
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Wim C J
authors.initials: WC
authors.lastname: Hop
authors.forename: Hester A
authors.initials: HA
authors.lastname: de Groot-Kruseman
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Lequin
authors.forename: Inge M
authors.initials: IM
authors.lastname: van der Sluis
authors.forename: Jos P M
authors.initials: JP
authors.lastname: Bökkerink
authors.forename: Jan A
authors.initials: JA
authors.lastname: Leeuw
authors.forename: Marrie C A
authors.initials: MC
authors.lastname: Bruin
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.forename: Anjo J P
authors.initials: AJ
authors.lastname: Veerman
authors.forename: Marry M
authors.initials: MM
authors.lastname: van den Heuvel-Eibrink
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D010020:Osteonecrosis / Q000139:chemically induced* / Q000175:diagnosis* / Q000000981:diagnostic imaging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011859:Radiography; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D003907:Dexamethasone