Page 128 - 2019_04-Haematologica-web

Ferrata Storti Foundation
Haematologica 2019 Volume 104(4):756-765
Acute Lymphoblastic Leukemia
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,1 Martin Schrappe,2 Alexander Claviez,2 Martin Zimmermann,3 Charlotte Niemeyer, 4Reinhard Kolb,5 Wolfgang Eberl,6 Frank Berthold,7 Eva Bergsträsser,8 Astrid Gnekow,9 Elisabeth Lassay,10 Peter Vorwerk,11 Melchior Lauten,12 Axel Sauerbrey,13 Johannes Rischewski,14 Andreas Beilken,3 Günter Henze,15 Wolfgang Korte16* and Anja Möricke2* for the THROMBOTECT Study Investigators†
1Children’s Hospital of Eastern Switzerland, Hematology and Oncology Department, St. Gallen, Switzerland; 2Department of Pediatrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein, Kiel, Germany; 3Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany; 4Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center - Faculty of Medicine, University of Freiburg, Germany; 5Department of Pediatrics, Zentrum für Kinder- und Jugendmedizin, Klinikum Oldenburg GmbH, Germany; 6Institute for Clinical Transfusion Medicine and Children’s Hospital, Klinikum Braunschweig GmbH, Germany; 7Department of Pediatric Hematology and Oncology, Children's Hospital, University of Cologne, Germany; 8Department of Pediatric Oncology, University Children's Hospital, Zurich, Switzerland; 9Hospital for Children and Adolescents, Klinikum Augsburg, Germany; 10Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Germany; 11Pediatric Oncology, Otto von Guericke University Children’s Hospital, Magdeburg, Germany; 12University Hospital Schleswig- Holstein, Department of Pediatrics, University of Lübeck, Germany; 13HELIOS Children's Hospital GmbH, Erfurt, Germany; 14Department of Oncology/Hematology, Children's Hospital, Cantonal Hospital Lucerne, Switzerland; 15Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Germany and 16Center for Laboratory Medicine and Hemostasis and Hemophilia Center, St. Gallen, Switzerland
*WK and AM share last authorship
†A complete list of the THROMBOTECT study investigators is provided in the Online Supplementary Appendix
ABSTRACT
Thromboembolism is a serious complication of induction therapy for childhood acute lymphoblastic leukemia. We prospectively com- pared 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-adapt- ed 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 throm- boembolism (8.0%) compared with those randomized to enoxaparin (3.5%; P=0.011) or antithrombin (1.9%; P<0.001). The proportion of patients who refused antithrombotic treatment as allocated was 3% in the unfractionated heparin or antithrombin arms, and 33% in the enoxaparin arm. Major hemorrhage occurred in eight patients (no differences between the groups). The 5-year event-free survival was 80.9±2.2% among patients
Correspondence:
JEANETTE GREINER
jeanette.greiner@kispisg.ch
Received: March 29, 2018. Accepted: September 27, 2018. Pre-published: September 27, 2018.
doi:10.3324/haematol.2018.194175
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/4/756
©2019 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
756
haematologica | 2019; 104(4)
ARTICLE