Thrombotic events revisited in children with acute lymphoblastic leukemia - Impact of concomitant Escherichia coli asparaginase/prednisone administration

Recently published data suggest that the prothrombin G20210A variant, the T T677 methylenetetrahydrofolate reductase genotype, the factor V G1691A muta tion, deficiencies of protein C, protein S, antithrombin, and elevated lipo protein (a) concentrations were associated with venous thromboembolism in c hildhood patients treated according to the BFM protocol. To unravel the rol e of these prothrombotic risk factors and different treatment modalities, t he present comparative study was performed in childhood leukemia patients o f the same living population. Four hundred and twenty consecutively recruit ed leukemic children (BFM n = 300; COALL n = 120) were enrolled in this stu dy with respect to the presence of prothrombotic risk factors and the occur rence of symptomatic venous thrombosis. No significant difference was found in the prevalence rates of thrombotic risk factors in the Caucasian popula tions studied. Symptomatic venous thromboembolism occurred in 11.6% of BFM patients compared with 2.5% in the COALL treatment group [odds ratio (OR)/9 5% confidence intervals (CI): 7.7/1.8-32.6; P = .005]. Including age, proth rombotic risk factors, central venous lines, treatment protocols, and anti- leukemic drugs in a logistic regression model, only the concomitant Escheri chia coli asparaginase/prednisone administration in leukemic children suffe ring from a prothrombotic risk factor was found to increase the rate of thr ombotic manifestations during leukemia treatment in patients of the same Ca ucasian origin (OR/95% Cl: 34.5/4.39-271.42; P = .0008). Based on the data presented here, we suggest the use of prednisone and E. coli asparaginase c oncomitantly administered in a leukemic patient suffering from a prothrombo tic risk factor to be responsible for the onset of venous thrombosis in the majority of cases. (C) 2001 Elsevier Science Ltd. All rights reserved.