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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

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 lym...

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Autores principales: Greiner, Jeanette, Schrappe, Martin, Claviez, Alexander, Zimmermann, Martin, Niemeyer, Charlotte, Kolb, Reinhard, Eberl, Wolfgang, Berthold, Frank, Bergsträsser, Eva, Gnekow, Astrid, Lassay, Elisabeth, Vorwerk, Peter, Lauten, Melchior, Sauerbrey, Axel, Rischewski, Johannes, Beilken, Andreas, Henze, Günter, Korte, Wolfgang, Möricke, Anja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ferrata Storti Foundation 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442986/
https://www.ncbi.nlm.nih.gov/pubmed/30262570
http://dx.doi.org/10.3324/haematol.2018.194175
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author Greiner, Jeanette
Schrappe, Martin
Claviez, Alexander
Zimmermann, Martin
Niemeyer, Charlotte
Kolb, Reinhard
Eberl, Wolfgang
Berthold, Frank
Bergsträsser, Eva
Gnekow, Astrid
Lassay, Elisabeth
Vorwerk, Peter
Lauten, Melchior
Sauerbrey, Axel
Rischewski, Johannes
Beilken, Andreas
Henze, Günter
Korte, Wolfgang
Möricke, Anja
author_facet Greiner, Jeanette
Schrappe, Martin
Claviez, Alexander
Zimmermann, Martin
Niemeyer, Charlotte
Kolb, Reinhard
Eberl, Wolfgang
Berthold, Frank
Bergsträsser, Eva
Gnekow, Astrid
Lassay, Elisabeth
Vorwerk, Peter
Lauten, Melchior
Sauerbrey, Axel
Rischewski, Johannes
Beilken, Andreas
Henze, Günter
Korte, Wolfgang
Möricke, Anja
author_sort Greiner, Jeanette
collection PubMed
description 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<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 assigned to antithrombin compared to 85.9±2.0% in the unfractionated heparin group (P=0.06), and 86.2±2.0% in the enoxaparin group (P=0.10). In conclusion, prophylactic use of antithrombin or enoxaparin significantly reduced thromboembolism. Despite the considerable number of patients rejecting the assigned treatment with subcutaneous injections, the result remains unambiguous. Thromboprophylaxis - for the present time primarily with enoxaparin - can be recommended for children and adolescents with acute lymphoblastic leukemia during induction therapy. Whether and how antithrombin may affect leukemia outcome remains to be determined.
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spelling pubmed-64429862019-04-12 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 Greiner, Jeanette Schrappe, Martin Claviez, Alexander Zimmermann, Martin Niemeyer, Charlotte Kolb, Reinhard Eberl, Wolfgang Berthold, Frank Bergsträsser, Eva Gnekow, Astrid Lassay, Elisabeth Vorwerk, Peter Lauten, Melchior Sauerbrey, Axel Rischewski, Johannes Beilken, Andreas Henze, Günter Korte, Wolfgang Möricke, Anja Haematologica Article 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<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 assigned to antithrombin compared to 85.9±2.0% in the unfractionated heparin group (P=0.06), and 86.2±2.0% in the enoxaparin group (P=0.10). In conclusion, prophylactic use of antithrombin or enoxaparin significantly reduced thromboembolism. Despite the considerable number of patients rejecting the assigned treatment with subcutaneous injections, the result remains unambiguous. Thromboprophylaxis - for the present time primarily with enoxaparin - can be recommended for children and adolescents with acute lymphoblastic leukemia during induction therapy. Whether and how antithrombin may affect leukemia outcome remains to be determined. Ferrata Storti Foundation 2019-04 /pmc/articles/PMC6442986/ /pubmed/30262570 http://dx.doi.org/10.3324/haematol.2018.194175 Text en Copyright© 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 internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.
spellingShingle Article
Greiner, Jeanette
Schrappe, Martin
Claviez, Alexander
Zimmermann, Martin
Niemeyer, Charlotte
Kolb, Reinhard
Eberl, Wolfgang
Berthold, Frank
Bergsträsser, Eva
Gnekow, Astrid
Lassay, Elisabeth
Vorwerk, Peter
Lauten, Melchior
Sauerbrey, Axel
Rischewski, Johannes
Beilken, Andreas
Henze, Günter
Korte, Wolfgang
Möricke, Anja
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442986/
https://www.ncbi.nlm.nih.gov/pubmed/30262570
http://dx.doi.org/10.3324/haematol.2018.194175
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