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Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-06-1901.
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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2529-2533
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Thromboembolic events in children with acute lymphoblastic
leukemia (BFM protocols): prednisone versus dexamethasone
administration
Ulrike Nowak-Göttl,
Elvira Ahlke,
Gudrun Fleischhack,
Dirk Schwabe,
Rosmarie Schobess,
Christiane Schumann, and
Ralf Junker
From Pediatric Hematology/Oncology, University
Hospitals Münster, Bonn, Frankfurt, and Halle; and from the
Institute of Clinical Chemistry and Laboratory Medicine and the
Institute of Arteriosclerosis Research, University Hospital
Münster, Germany.
Alterations in hemostasis leading to symptomatic thromboembolism
have been observed in patients with acute lymphoblastic leukemia (ALL)
receiving Escherichia coli asparaginase (CASP) combined with steroids. Moreover, hereditary prothrombotic risk factors are
associated with an increased risk for venous thromboembolism in
pediatric ALL patients treated according to the BFM 90/95 protocols (including CASP combined with prednisone during induction therapy). To
assess whether the thromboembolic risk associated with established prothrombotic risk factors is modified by treatment modalities (prednisone or dexamethasone), the present analysis was performed. Three hundred thirty-six consecutively recruited leukemic children treated according to different BFM protocols (PRED group, n = 280, 60 mg/m2 prednisone; DEXA group, n = 56, 10 mg/m2 dexamethasone during induction therapy) were studied.
Study end point was the onset of symptomatic vascular accidents during
induction therapy. Cumulative thromboembolism-free survival was
significantly reduced in children in the PRED group (thrombosis
frequency, 10.4%) compared with children in the DEXA group (thrombosis
frequency, 1.8%; P = .028). Although no significant
difference was found in the overall prevalence of prothrombotic risk
factors, 46.5% of patients in the PRED group who experienced
thromboembolic events were carriers of a prothrombotic risk factor,
whereas no carrier in the DEXA group had a thromboembolism. At the time
of maximum CASP activity, fibrinogen and activities of antithrombin,
plasminogen, and protein S were significantly reduced in the PRED
group. No significant correlation could be found between CASP activity
and levels of coagulation factors. In conclusion, the use of
dexamethasone instead of prednisone, administered with CASP,
significantly reduced the onset of venous thromboembolism.
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