title: Thromboembolism in children with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute protocols: effect of age and risk stratification of disease.
abstract: Children with acute lymphoblastic leukaemia (ALL) are at increased risk for thromboembolism (TE). Identification of a susceptible population is crucial for effective thromboprophylaxis. However, the risk factors for ALL-associated TE are unclear. Concomitant asparaginase (ASP) and steroid therapy has been shown to increase the incidence of TE. Dana-Farber Cancer Institute (DFCI)-ALL protocols use a combination of ASP and steroids during the postinduction intensification phase when high-risk (HR) patients receive thrice the steroid-dose given to standard-risk (SR) patients. We studied prospectively assembled cohorts of children treated on two consecutive DFCI-ALL protocols to define the risk factors for symptomatic TE. Ten (11%) of 91 patients developed symptomatic TE; eight (seven HR) during intensification. Seven (44%) of 16 older patients (>/=10 years) compared with three of 75 (4%) younger patients developed TE (P < 0.0001). Nine of 35 (26%) HR and one of 56 (2%) SR patients developed TE (P = 0.0006). Gender, ALL-immunophenotype, steroid-type or ASP dosing schedule did not alter the risk but older age and HR-disease were factors predisposing to TE associated with DFCI-ALL protocols. Age-related risk may partly reflect the effect of ALL-risk stratification. Higher dose steroids combined with ASP may lead to an increased risk of TE in HR patients.
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, McMaster University, Hamilton, ON, Canada. athaleu@mcmaster.ca
authors.forename: Uma H
authors.initials: UH
authors.lastname: Athale
authors.forename: Sabrina A
authors.initials: SA
authors.lastname: Siciliano
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Barr
authors.forename: Anthony K C
authors.initials: AK
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D012307:Risk Factors; D013923:Thromboembolism / Q000139:chemically induced*; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D001215:Asparaginase; D011241:Prednisone