PDF herunterladen
Thromb Haemost 2020; 120(02): 322-328
DOI: 10.1055/s-0039-3400303
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Development of a Clinical Prediction Rule for Venous Thromboembolism in Patients with Acute Leukemia

Fatimah Al-Ani
1   Division of Hematology, Department of Medicine, Western University, London, Ontario, Canada
,
Yimin Pearl Wang
1   Division of Hematology, Department of Medicine, Western University, London, Ontario, Canada
,
Alejandro Lazo-Langner 
1   Division of Hematology, Department of Medicine, Western University, London, Ontario, Canada
2   Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
› Institutsangaben 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.
Weitere Informationen

Publikationsverlauf

21. Mai 2019

26. September 2019

Publikationsdatum:
01. Januar 2020 (online)

    Lizenzen und Reprints

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.

Keywords

acute leukemia - venous thromboembolism - prediction - score
 

  • 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
    CrossrefPubMedGoogle Scholar
  • 2 Falanga A, Marchetti M, Russo L. Venous thromboembolism in the hematologic malignancies. Curr Opin Oncol 2012; 24 (06) 702-710
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 18 Carrier M, Abou-Nassar K, Mallick R. , et al. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2018
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar