THROMBOTECT – a randomized study comparing low molecular weight heparin, antithrombin and unfractionated heparin for thromboprophylaxis during induction therapy of acute lymphoblastic leukemia in children and adolescents
Jeanette Greiner,
Martin Schrappe,
Alexander Claviez,
Martin Zimmermann,
Charlotte Niemeyer,
Reinhard Kolb,
Wolfgang Eberl,
Frank Berthold,
Eva Bergsträsser,
Astrid Gnekow,
Elisabeth Lassay,
Peter Vorwerk,
Melchior Lauten,
Axel Sauerbrey,
Johannes Rischewski,
Andreas Beilken,
Günter Henze,
Wolfgang Korte,
Anja Möricke,
for the THROMBOTECT Study Investigators
Affiliations
Jeanette Greiner
Children’s Hospital of Eastern Switzerland, Hematology and Oncology Department, St. Gallen, Switzerland
Martin Schrappe
Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
Alexander Claviez
Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
Martin Zimmermann
Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany
Charlotte Niemeyer
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - Faculty of Medicine, University of Freiburg, Germany
Reinhard Kolb
Department of Pediatrics, Zentrum für Kinder- und Jugendmedizin, Klinikum Oldenburg GmbH, Germany
Wolfgang Eberl
Institute for Clinical Transfusion Medicine and Children’s Hospital, Klinikum Braunschweig GmbH, Germany
Frank Berthold
Department of Pediatric Hematology and Oncology, Children’s Hospital, University of Cologne, Germany
Eva Bergsträsser
Department of Pediatric Oncology, University Children’s Hospital, Zurich, Switzerland
Astrid Gnekow
Hospital for Children and Adolescents, Klinikum Augsburg, Germany
Elisabeth Lassay
Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Germany
Peter Vorwerk
Pediatric Oncology, Otto von Guericke University Children’s Hospital, Magdeburg, Germany
Melchior Lauten
University Hospital Schleswig-Holstein, Department of Pediatrics, University of Lübeck, Germany
Axel Sauerbrey
HELIOS Children’s Hospital GmbH, Erfurt, Germany
Johannes Rischewski
Department of Oncology/Hematology, Children’s Hospital, Cantonal Hospital Lucerne, Switzerland
Andreas Beilken
Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany
Günter Henze
Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Germany
Wolfgang Korte
Center for Laboratory Medicine and Hemostasis and Hemophilia Center, St. Gallen, Switzerland
Anja Möricke
Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany
Thromboembolism is a serious complication of induction therapy for childhood acute lymphoblastic leukemia. We prospectively compared the efficacy and safety of antithrombotic interventions in the consecutive leukemia trials ALL-BFM 2000 and AIEOP-BFM ALL 2009. Patients with newly diagnosed acute lymphoblastic leukemia (n=949, age 1 to 18 years) were randomized to receive low-dose unfractionated heparin, prophylactic low molecular weight heparin (enoxaparin) or activity-adapted antithrombin throughout induction therapy. The primary objective of the study was to determine whether enoxaparin or antithrombin reduces the incidence of thromboembolism as compared to unfractionated heparin. The principal safety outcome was hemorrhage; leukemia outcome was a secondary endpoint. Thromboembolism occurred in 42 patients (4.4%). Patients assigned to unfractionated heparin had a higher risk of thromboembolism (8.0%) compared with those randomized to enoxaparin (3.5%; P=0.011) or antithrombin (1.9%; P
