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THROMBOTECT - a randomized study comparing low molecular weight heparin, antithrombin and unfractionated heparin for thromboprophylaxis during inudction 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 (2019). THROMBOTECT - a randomized study comparing low molecular weight heparin, antithrombin and unfractionated heparin for thromboprophylaxis during inudction therapy of acute lymphoblastic leukemia in children and adolescents. Haematologica, 104(4):756-765.

Abstract

Thromboembolism is a serious complication of induction therapy for childhood acute lymphoblastic leukemia. We prospectively compared 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. Primary objective was to test whether enoxaparin or antithrombin reduce the incidence of thromboembolism as compared to unfractionated heparin. 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, and 33% in the enoxaparin arm. Major hemorrhage occurred in eight patients (no differences between the groups). 5-year-event free survival was 80.9±2.2% if assigned to antithrombin compared to 85.9±2.0% in the unfractionated heparin (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 nonambiguous. 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.

Abstract

Thromboembolism is a serious complication of induction therapy for childhood acute lymphoblastic leukemia. We prospectively compared 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. Primary objective was to test whether enoxaparin or antithrombin reduce the incidence of thromboembolism as compared to unfractionated heparin. 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, and 33% in the enoxaparin arm. Major hemorrhage occurred in eight patients (no differences between the groups). 5-year-event free survival was 80.9±2.2% if assigned to antithrombin compared to 85.9±2.0% in the unfractionated heparin (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 nonambiguous. 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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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 April 2019
Deposited On:17 Jan 2019 11:00
Last Modified:13 Oct 2019 05:54
Publisher:Ferrata Storti Foundation
ISSN:0390-6078
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3324/haematol.2018.194175
PubMed ID:30262570

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