Thromboembolism in children with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute protocols: effect of age and risk stratification of disease

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.