Venous thromboembolism in pediatric patients with acute lymphoblastic leukemia under chemotherapy treatment. Risk factors and usefulness of thromboprophylaxis. Results of LAL-SEHOP-PETHEMA-2013.
acute lymphoblastic leukemia
children
prophylaxis
thrombophilia
thrombosis
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
09
03
2022
received:
07
12
2021
accepted:
10
03
2022
pubmed:
16
3
2022
medline:
25
5
2022
entrez:
15
3
2022
Statut:
ppublish
Résumé
Symptomatic venous thromboembolism (VTE) is diagnosed in 3%-14% of patients during pediatric acute lymphoblastic leukemia (ALL) therapy. There are well-known risk factors, but the role of others as inherited thrombophilia is still controversial. Prophylaxis with low molecular weight heparin (LMWH) has been described, but its use is not globally accepted. A retrospective multicentric study in ALL patients 1-18 years old following SEHOP-PETHEMA-2013 treatment guideline was performed to evaluate VTE rate, anticoagulant treatment, outcome, risk factors, and safety and usefulness of LMWH administration as primary thromboprophylaxis in children with inherited thrombophilia. A total of 652 patients were included in the study. VTE incidence was 8.7%. Most of the cases occurred during induction therapy associated with central venous catheter. Univariant analysis showed that family history of thrombosis, presence of mediastinal mass, high-risk treatment group, and inherited thrombophilia were statistically significant risk factors. LMWH administration seemed to decrease VTE rate in patients with inherited thrombophilia and those with T-cell ALL phenotype. Most of the VTE cases occurred in patients without inherited thrombophilia, but when it is present, the VTE risk is higher. LMWH administration was useful to decrease VTE in these patients.
Identifiants
pubmed: 35289066
doi: 10.1111/jth.15699
pii: S1538-7836(22)00194-5
doi:
Substances chimiques
Anticoagulants
0
Heparin, Low-Molecular-Weight
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1390-1399Informations de copyright
© 2022 International Society on Thrombosis and Haemostasis.
Références
Nowak-Göttl U, Kenet G, Mitchell LG. Thrombosis in childhood acute lymphoblastic leukaemia: epidemiology, aetiology, diagnosis, prevention and treatment. Best Pract Res Clin Haematol. 2009;22:103-114.
Caruso V, Iacoviello L, Di Castelnuovo A, et al. Thrombotic complications in childhood acute lymphoblastic leukemia: a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood. 2006;108:2216-2222.
Athale UH, Mizrahi T, Laverdière C, et al. Impact of baseline clinical and laboratory features on the risk of thrombosis in children with acute lymphoblastic leukemia: a prospective evaluation. Pediatr Blood Cancer. 2018;65:1-8.
Klaassen ILM, Lauw MN, Fiocco M, et al. Venous thromboembolism in a large cohort of children with acute lymphoblastic leukemia: risk factors and effect on prognosis. Res Pract Thromb Haemosts. 2019;3:234-241.
Rühle F, Stoll M. Advances in predicting venous thromboembolism risk in children. Br J Haematol. 2018;180:654-665.
Mateos MK, Trahair TN, Mayoh C, et al. Risk factors for symptomatic venous thromboembolism during therapy for childhood acute lymphoblastic leukemia. Thromb Res. 2019;178:132-138.
Mitchell L, Andrew M, Hanna K, et al. Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving l-asparaginase for acute lymphoblastic leukemia. Results of the PAARKA study. Thromb Haemost. 2003;90:235-244.
Mitchell L, Lambers M, Flege S, et al. Validation of a predictive model for identifying an increased risk for thromboembolism in children with acute lymphoblastic leukemia: results of a multicenter cohort study. Blood. 2010;115:4999-5004.
Elhasid R, Lanir N, Sharon R, et al. Prophylactic therapy with enoxaparin during L-asparaginase treatment in children with acute lymphoblastic leukemia. Blood Coag Fibrinol. 2001;12:367-370.
Barzilai-Birenboim S, Arad-Cohen N, Nirel R, et al. Thrombophilia screening and thromboprophylaxis may benefit specific ethnic subgroups with paediatric acute lymphoblastic leukaemia. Br J Haematol. 2019;184:994-998.
Sifontes MT, Nuss R, Hunger SP, Wilimas J, Jacobson LJ, Manco-Johnson MJ. The factor V Leiden mutation in children with cancer and thrombosis. Br J Haematol. 1997;96:484-489.
Wermes C, von Depka PM, Lichtinghagen R, Barthels M, Welte K, Sykora KW. Clinical relevance of genetic risk factors for thrombosis in paediatric oncology patients with central venous catheters. Eur J Pediatr. 1999;158:143-147.
Mauz-Körholz C, Junker R, Göbel U, Nowak-Göttl U. Prothrombotic risk factors in children with acute lymphoblastic leukemia treated with delayed E. coli asparaginase (COALL-92 and 97 protocols). Thromb Haemost. 2000;83:840-843.
Athale U. Thrombosis in pediatric cancer: identifying the risk factors to improve care. Expert Rev Hematol. 2013;6:599-609.
Athale UH, Laverdiere C, Nayiager T, et al. Evaluation for inherited and acquired prothrombotic defects predisposing to symptomatic thromboembolism in children with acute lymphoblastic leukemia: a protocol for a prospective, observational, cohort study. BMC Cancer. 2017;17:1-14.
Levy-Mendelovich S, Barg AA, Kenet G. Thrombosis in pediatric patients with leukemia. Thromb Res. 2018;164:S94-S97.
Pelland-Marcotte MC, Kulkarni K, Athale UH, Pole JD, Brandão LR, Sung L. Thrombosis is associated with worse survival in children with acute lymphoblastic leukemia: a report from CYP-C. Am J Hematol. 2021;96:796-804.
Sibson KR, Biss TT, Furness CL, et al. BSH guideline: management of thrombotic and haemostatic issues in paediatric malignancy. Br J Haematol. 2018;180:511-525.
Tullius BP, Athale U, van Ommen CH, Chan AKC, Palumbo JS, Balagtas JMS. The identification of at-risk patients and prevention of venous thromboembolism in pediatric cancer: guidance from the SSC of the ISTH. J Thromb Haemost. 2018;16:175-180.
Payne JH, Vora AJ. Thrombosis and acute lymphoblastic leukaemia. Br J Haematol. 2007;138:430-445.
Astwood E, Vora A. Personal practice: How we manage the risk of bleeding and thrombosis in children and young adults with acute lymphoblastic leukaemia. Br J Haematol. 2011;152:505-511.
Attard C, Ignjatovic V. Primary thromboprophylaxis in children with cancer: a road less travelled. Thromb Haemost. 2019;119:1894-1896.
van Ommen CH, Nowak-Göttl U. Inherited thrombophilia in pediatric venous thromboembolic disease: why and who to test. Front Pediatr. 2017;5:50.
Harlev D, Zaidman I, Sarig G, Weyl Ben Arush M, Brenner B, Elhasid R. Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment. Thromb Res. 2010;126:93-97.
Greiner J, Schrappe M, Claviez A, et al. 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. Haematologica. 2019;104:756-765.
Pelland-Marcotte M-C, Tole S, Pechlivanoglou P, Brandão LR. Effectiveness and safety of primary thromboprophylaxis in children with cancer: a systematic review of the literature and network meta-analysis. Thromb Haemost. 2019;119(12):2034-2042.
Mesegué M, Alonso-Saladrigues A, Pérez-Jaume S, et al. Lower incidence of clinical allergy with PEG-asparaginase upfront versus the sequential use of native E. coli asparaginase followed by PEG-ASP in pediatric patients with acute lymphoblastic leukemia. Hematol Oncol. 2021;39(5):687-696.
Mitchell LG, Goldenberg NA, Male C, Kenet G, Monagle P, Nowak-Göttl U. Definition of clinical efficacy and safety outcomes for clinical trials in deep venous thrombosis and pulmonary embolism in children. J Thromb Haemost. 2011;9:1856-1858.
Sarangi SN, Gaballah M, Nolfi-Donegan D, et al. Primary thromboprophylaxis to prevent thrombotic events in pediatric oncology patients with a malignant mediastinal mass. Pediatr Blood Cancer. 2021;68(12):e29360.
Rank CU, Toft N, Tuckuviene R, et al. Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years. Blood. 2018;131:2475-2485.
Nowak-Göttl U, Sträter R, Heinecke A, et al. Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood. Blood. 1999;94:3678-3682.
Giordano P, Saracco P, Grassi M, et al. Recommendations for the use of long-term central venous catheter (CVC) in children with hemato-oncological disorders: management of CVC-related occlusion and CVC-related thrombosis. On behalf of the coagulation defects working group and the supportive the. Ann Hematol. 2015;94:1765-1776.
Meister B, Kropshofer G, Klein-Franke A, Strasak AM, Hager J, Streif W. Comparison of low-molecular-weight heparin and antithrombin versus antithrombin alone for the prevention of symptomatic venous thromboembolism in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008;50:298-303.
Bosch A, Albisetti M. Management of venous thromboembolism in children: current recommendations and therapeutic options. Ther Clin Risk Manag. 2020;16:673-679.
Monagle P, Cuello CA, Augustine C, et al. American Society of hematology 2018 guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism. Blood Adv. 2018;2:3292-3316.