Thromb Haemost 2015; 113(01): 201-208
DOI: 10.1160/TH13-12-1020
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Implications of cytogenetics for venous thromboembolism in acute myeloid leukaemia

Yun-Gyoo Lee*
1   Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
2   Department of Internal Medicine, Kangbuk Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
,
Inho Kim*
1   Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Ji-hyun Kwon
1   Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Sung Soo Yoon
1   Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Seongyang Park
1   Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
,
Leo Song
3   University College Dublin School of Medicine, Dublin, Ireland
,
Jae-Ho Yoon
4   Department of Hematology, Cancer Research Institute, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
,
Seung-Hwan Shin
4   Department of Hematology, Cancer Research Institute, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
,
Woo-Sung Min
4   Department of Hematology, Cancer Research Institute, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
,
Hee-Je Kim
4   Department of Hematology, Cancer Research Institute, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
› Author Affiliations
Further Information

Publication History

Received: 12 December 2013

Accepted after major revision: 22 August 2014

Publication Date:
27 November 2017 (online)

Summary

Due to the high risk of thrombocytopenia and haemorrhage, thrombotic complications have received little attention in patients with acute myeloid leukemia (AML). Furthermore, the predictive role of cytogenetics on venous thromboembolism (VTE) has largely been ignored. This study aimed to evaluate the incidence, risk factors, and prognostic aspects of VTE in AML. A total of 811 consecutive patients with AML were enrolled and analysed retrospectively. Cox time-dependent covariate regression analysis was used to identify the significant predictors of VTE development. To minimise potential confounding factors, we used propensity-score matching to compare overall survival between patients with and without VTE. The six-month and one-year cumulative incidences of VTE were 3.1 % (95 % confidence interval [CI], 2.0–4.7) and 3.9 % (95 % CI, 2.6–5.7), respectively. Of the 26 cases of VTE, 22 (85 %) developed within 6 months of leukemia diagnosis and 13 (50 %) were catheter-related. In multivariate analysis, advanced age (≥ 65 years) (hazard ratio [HR], 2.70; p = 0.03) and increasing cytogenetic risk (common HR, 1.84; p = 0.05) were independent predictors of VTE. There was no significant association between VTE development and decreased survival (p = 0.32 for matched analysis). Advanced age and increasing cytogenetic risk, well-known predictors for clinical outcome in AML, were also independent risk factors of VTE development. Our results suggest that VTE does not hold prognostic implications for AML.

* Y.G. Lee and I. Kim contributed equally to this work.


 
  • References

  • 1 Heit JA, Silverstein MD, Mohr DN. et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160: 809-815.
  • 2 Khorana AA, Francis CW, Culakova E. et al. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104: 2822-2829.
  • 3 Blom JW, Doggen CJ, Osanto S. et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. J Am Med Assoc 2005; 293: 715-722.
  • 4 Khorana AA, Francis CW, Culakova E. et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007; 05: 632-634.
  • 5 Falanga A, Marchetti M. Venous thromboembolism in the hematologic malignancies. J Clin Oncol 2009; 27: 4848-4857.
  • 6 Ku GH, White RH, Chew HK. et al. Venous thromboembolism in patients with acute leukaemia: incidence, risk factors, and effect on survival. Blood 2009; 113: 3911-3917.
  • 7 Chew HK, Wun T, Harvey D. et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006; 166: 458-464.
  • 8 Ziegler S, Sperr WR, Knobl P. et al. Symptomatic venous thromboembolism in acute leukaemia. Incidence, risk factors, and impact on prognosis. Thromb Res 2005; 115: 59-64.
  • 9 De Stefano V, Sora F, Rossi E. et al. The risk of thrombosis in patients with acute leukaemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost 2005; 03: 1985-1992.
  • 10 Mohren M, Markmann I, Jentsch-Ullrich K. et al. Increased risk of venous thromboembolism in patients with acute leukaemia. Br J Cancer 2006; 94: 200-202.
  • 11 Melillo L, Grandone E, Colaizzo D. et al. Symptomatic venous thromboembolism and thrombophilic status in adult acute leukaemia: a single-center experience of 114 patients at diagnosis. Acta Haematol 2007; 117: 215-220.
  • 12 Byrd JC, Mrozek K, Dodge RK. et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukaemia: results from Cancer and Leukaemia Group B (CALGB 8461). Blood 2002; 100: 4325-4336.
  • 13 Grimwade D, Walker H, Oliver F. et al. The importance of diagnostic cytogen-etics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood 1998; 92: 2322-2333.
  • 14 Slovak ML, Kopecky KJ, Cassileth PA. et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukaemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 2000; 96: 4075-4083.
  • 15 Piccirillo JF, Tierney RM, Costas I. et al. Prognostic importance of comorbidity in a hospital-based cancer registry. J Am Med Assoc 2004; 291: 2441-2447.
  • 16 Khorana AA, Kuderer NM, Culakova E. et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111: 4902-4907.
  • 17 O’Donnell MR, Abboud CN, Altman J. et al. Acute myeloid leukaemia. J Natl Compr Canc Netw 2012; 10: 984-1021.
  • 18 Esmon CT. The interactions between inflammation and coagulation. Br J Hae-matol 2005; 131: 417-430.
  • 19 Levi M, van der Poll T, Buller HR. Bidirectional relation between inflammation and coagulation. Circulation 2004; 109: 2698-2704.
  • 20 Del Principe MI, Buccisano F, Maurillo L. et al. Infections increase the risk of central venous catheter-related thrombosis in adult acute myeloid leukaemia. Thromb Res 2013; 132: 511-514.