Abstract
Background Venous thromboembolism (VTE) is an important complication for treatment of acute lymphoblastic leukemia (ALL) in children. Especially, ALL treatment, with therapeutics such as asparaginase and steroids, increases the thrombotic risk by reduction in procoagulant and anticoagulant proteins. Replacement of deficient natural anticoagulants by administration of fresh frozen plasma (FFP) may have a preventive effect on the occurrence of VTE. Methods We retrospectively analyzed all consecutive children (≤18 years) with ALL, treated on the Dutch Childhood Oncology Group (DCOG) ALL-9 and ALL-10 protocols at the Emma Children's Hospital Academic Medical Center between February 1997 and January 2012, to study the effect of FFP on VTE incidence, antithrombin and fibrinogen plasma levels, and VTE risk factors. Results In total, 18/205 patients developed VTE (8.8%; 95% confidence interval [CI]: 4.9–12.7%). In all patients, VTE occurred after asparaginase administration. In total, 82/205 patients (40%) received FFP. FFP supplementation did not prevent VTE or alter plasma levels of antithrombin or fibrinogen. In the multivariate analysis, VTE occurred significantly more frequently in children ≥12 years (odds ratio [OR]: 3.89; 95% CI: 1.29–11.73) and treated according to the ALL-10 protocol (OR: 3.71; 95% CI: 1.13–12.17). Conclusion FFP supplementation does not seem to be beneficial in the prevention of VTE in pediatric ALL patients. In addition, age ≥12 years and treatment according to the DCOG ALL-10 protocol with intensive and prolonged administration of asparaginase in combination with prednisone are risk factors. There is a need for effective preventive strategies in ALL patients at high risk for VTE.
Highlights
Venous thromboembolism (VTE) is an important complication for treatment of acute lymphoblastic leukemia (ALL) in children
Age !12 years and treatment according to the Dutch Childhood Oncology Group (DCOG) ALL-10 protocol with intensive and prolonged administration of asparaginase in combination with prednisone are risk factors
Eighty-one patients were excluded: 53 patients were mainly treated outside the EKZ/Academic Medical Center (AMC) after diagnosis, 15 patients were treated according to a different protocol, and 13 medical records were not available
Summary
Venous thromboembolism (VTE) is an important complication for treatment of acute lymphoblastic leukemia (ALL) in children. Treatment of ALL enhances the thrombotic risk.[2] Most thrombotic events occur during the administration of asparaginase and steroid therapy. Both drugs are vital components of ALL treatment protocols. The total amount of asparagine is decreased leading to reduction of protein synthesis, causing cell dead of the lymphoblasts. Due to reduced protein synthesis, both procoagulant and anticoagulant proteins are reduced, especially antithrombin (AT).[3] In addition, asparaginase seems to cause thrombin initiation by upregulating tissue factor as a result of activation of white cells and endothelium. ALL treatment, with therapeutics such as asparaginase and steroids, increases the thrombotic risk by reduction in procoagulant and anticoagulant proteins. Replacement of deficient natural anticoagulants by administration of fresh frozen plasma (FFP) may have a preventive effect on the occurrence of VTE
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