Subscribe to RSS
DOI: 10.1055/s-0039-3400303
Development of a Clinical Prediction Rule for Venous Thromboembolism in Patients with Acute Leukemia
Funding This study was funded by the Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network which receives grant funding from the Canadian Institutes for Health Research (Grant/Award number “CDT 142654”). F.A.-A was supported by a fellowship from the CanVECTOR Network. A.L.-L. is an investigator of the CanVECTOR Network.Publication History
21 May 2019
26 September 2019
Publication Date:
01 January 2020 (online)
Abstract
Risk factors for venous thromboembolism in patients with solid tumors are well studied; however, studies in patients with acute leukemia are lacking. We conducted a retrospective cohort study of adult patients diagnosed with acute myeloid leukemia and acute lymphoblastic leukemia diagnosed between June 2006 and June 2017 at a tertiary care center in Canada. Potential predictors of venous thromboembolism were evaluated using logistic regression and a risk score was derived based on weighed variables and compared using survival analysis. Internal validation was conducted using nonparametric bootstrapping. A total of 501 leukemia patients (427 myeloid and 74 lymphoblastic) were included. Venous thromboembolism occurred in 77(15.3%) patients with 71 events occurring in the first year. A prediction score was derived and validated and it included: previous history of venous thromboembolism (3 points), lymphoblastic leukemia (2 points), and platelet count > 50 × 109/L at the time of diagnosis (1 point). The overall cumulative incidence of venous thromboembolism was 44% in the high-risk group (≥ 3 points) versus 10.5% in the low-risk group (0–2 points) and it was consistent at different follow-up periods (log-rank p < 0.001). We derived and internally validated a predictive score of venous thromboembolism risk in acute leukemia patients.
-
References
- 1 Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006; 166 (04) 458-464
- 2 Falanga A, Marchetti M, Russo L. Venous thromboembolism in the hematologic malignancies. Curr Opin Oncol 2012; 24 (06) 702-710
- 3 Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111 (10) 4902-4907
- 4 Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007; 5 (03) 632-634
- 5 Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343 (25) 1846-1850
- 6 Ku GH, White RH, Chew HK, Harvey DJ, Zhou H, Wun T. Venous thromboembolism in patients with acute leukemia: incidence, risk factors, and effect on survival. Blood 2009; 113 (17) 3911-3917
- 7 Ziegler S, Sperr WR, Knöbl P. , et al. Symptomatic venous thromboembolism in acute leukemia. Incidence, risk factors, and impact on prognosis. Thromb Res 2005; 115 (1-2): 59-64
- 8 Melillo L, Grandone E, Colaizzo D, Cappucci F, Valvano MR, Cascavilla N. Symptomatic venous thromboembolism and thrombophilic status in adult acute leukemia: a single-center experience of 114 patients at diagnosis. Acta Haematol 2007; 117 (04) 215-220
- 9 Mohren M, Markmann I, Jentsch-Ullrich K, Koenigsmann M, Lutze G, Franke A. Increased risk of venous thromboembolism in patients with acute leukaemia. Br J Cancer 2006; 94 (02) 200-202
- 10 Vu K, Luong NV, Hubbard J. , et al. A retrospective study of venous thromboembolism in acute leukemia patients treated at the University of Texas MD Anderson Cancer Center. Cancer Med 2015; 4 (01) 27-35
- 11 Refaei M, Fernandes B, Brandwein J, Goodyear MD, Pokhrel A, Wu C. Incidence of catheter-related thrombosis in acute leukemia patients: a comparative, retrospective study of the safety of peripherally inserted vs. centrally inserted central venous catheters. Ann Hematol 2016; 95 (12) 2057-2064
- 12 Lyman GH, Bohlke K, Khorana AA. , et al; American Society of Clinical Oncology. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline update 2014. J Clin Oncol 2015; 33 (06) 654-656
- 13 Palumbo A, Rajkumar SV, Dimopoulos MA. , et al; International Myeloma Working Group. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 2008; 22 (02) 414-423
- 14 Khorana AA, Francis CW, Culakova E, Lyman GH. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104 (12) 2822-2829
- 15 Wasson JH, Sox HC, Neff RK, Goldman L. Clinical prediction rules. Applications and methodological standards. N Engl J Med 1985; 313 (13) 793-799
- 16 Henderson AR. The bootstrap: a technique for data-driven statistics. Using computer-intensive analyses to explore experimental data. Clin Chim Acta 2005; 359 (1-2): 1-26
- 17 Steyerberg EW, Harrell Jr FE, Borsboom GJ, Eijkemans MJ, Vergouwe Y, Habbema JD. Internal validation of predictive models: efficiency of some procedures for logistic regression analysis. J Clin Epidemiol 2001; 54 (08) 774-781
- 18 Carrier M, Abou-Nassar K, Mallick R. , et al. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2018
- 19 Mirza S, Yun S, Al Ali N. , et al. Validation of the Khorana score in acute myeloid leukemia patients: a single institution experience. Blood 2018; 132 (Suppl. 01) 2278-2278
- 20 Agnelli G, Bolis G, Capussotti L. , et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg 2006; 243 (01) 89-95
- 21 Connolly GC, Khorana AA. Emerging risk stratification approaches to cancer-associated thrombosis: risk factors, biomarkers and a risk score. Thromb Res 2010; 125 (Suppl. 02) S1-S7
- 22 Louzada ML, Carrier M, Lazo-Langner A. , et al. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. Circulation 2012; 126 (04) 448-454
- 23 James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol 2006; 194 (05) 1311-1315
- 24 Caruso V, Iacoviello L, Di Castelnuovo A, Storti S, Donati MB. Venous thrombotic complications in adults undergoing induction treatment for acute lymphoblastic leukemia: results from a meta-analysis. J Thromb Haemost 2007; 5 (03) 621-623
- 25 Sibai H, Seki JT, Wang TQ. , et al. Venous thromboembolism prevention during asparaginase-based therapy for acute lymphoblastic leukemia. Curr Oncol 2016; 23 (04) e355-e361
- 26 Beinart G, Damon L. Thrombosis associated with L-asparaginase therapy and low fibrinogen levels in adult acute lymphoblastic leukemia. Am J Hematol 2004; 77 (04) 331-335
- 27 De Stefano V, Sorà F, Rossi E. , et al. The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost 2005; 3 (09) 1985-1992
- 28 Truelove E, Fielding AK, Hunt BJ. The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia. Leukemia 2013; 27 (03) 553-559
- 29 Hunault-Berger M, Chevallier P, Delain M. , et al; GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang). Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study. Haematologica 2008; 93 (10) 1488-1494
- 30 Sylman JL, Mitrugno A, Tormoen GW, Wagner TH, Mallick P, McCarty OJT. Platelet count as a predictor of metastasis and venous thromboembolism in patients with cancer. Converg Sci Phys Oncol 2017; 3 (02) 023001
- 31 Barbui T, Finazzi G, Falanga A. The impact of all-trans-retinoic acid on the coagulopathy of acute promyelocytic leukemia. Blood 1998; 91 (09) 3093-3102
- 32 Dombret H, Scrobohaci ML, Daniel MT. , et al. In vivo thrombin and plasmin activities in patients with acute promyelocytic leukemia (APL): effect of all-trans retinoic acid (ATRA) therapy. Leukemia 1995; 9 (01) 19-24
- 33 Tallman MS, Lefèbvre P, Baine RM. , et al. Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia. J Thromb Haemost 2004; 2 (08) 1341-1350
- 34 Libourel EJ, Klerk CPW, van Norden Y. , et al. Disseminated intravascular coagulation at diagnosis is a strong predictor for thrombosis in acute myeloid leukemia. Blood 2016; 128 (14) 1854-1861
- 35 Lee YG, Kim I, Kwon JH. , et al. Implications of cytogenetics for venous thromboembolism in acute myeloid leukaemia. Thromb Haemost 2015; 113 (01) 201-208
- 36 Zakai NA, Wright J, Cushman M. Risk factors for venous thrombosis in medical inpatients: validation of a thrombosis risk score. J Thromb Haemost 2004; 2 (12) 2156-2161