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Thrombosis in patients with post-polycythemia vera myelofibrosis: incidence and risk factors

  • Author Footnotes
    1 GST and YZ contributed equally to this work.
    Guangshuai Teng
    Footnotes
    1 GST and YZ contributed equally to this work.
    Affiliations
    Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
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  • Author Footnotes
    1 GST and YZ contributed equally to this work.
    Yuan Zhou
    Footnotes
    1 GST and YZ contributed equally to this work.
    Affiliations
    State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China

    Tianjin Key Laboratory of Gene Therapy for Blood Diseases, Tianjin 300020, China

    Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, China

    Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, China
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  • Yuhui Zhang
    Affiliations
    Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
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  • Naibo Hu
    Affiliations
    Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
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  • Tong Liu
    Affiliations
    Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
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  • Yingdi Han
    Affiliations
    Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
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  • Chao Gao
    Affiliations
    Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
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  • Lei Zhang
    Correspondence
    Correspondence to: L. Zhang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
    Affiliations
    State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China

    Tianjin Key Laboratory of Gene Therapy for Blood Diseases, Tianjin 300020, China

    CAMS Key Laboratory of Gene Therapy for Blood Diseases, China

    Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, China

    Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, China
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  • Jie Bai
    Correspondence
    Corresponding author.
    Affiliations
    Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
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  • Author Footnotes
    1 GST and YZ contributed equally to this work.
Published:February 12, 2022DOI:https://doi.org/10.1016/j.thromres.2022.02.006

      Highlights

      • Patients with post-PV MF demonstrated a higher incidence of thrombosis, especially venous thrombosis.
      • JAK2V617F allele burden ≥75% associated with venous thrombosis in post-PV MF.
      • ≥1 DTA gene mutation in post-PV MF may increase the risk for thrombosis, especially the ASXL1 mutation.
      • Palpable splenomegaly was a risk factor for thrombosis in post-PV MF.
      • According to risk factor for thrombosis, a prognostic model was developed in post-PV MF.

      Abstract

      Introduction

      Post-polycythemia vera (PV) myelofibrosis (Post-PV MF) is an advanced phase of natural progression of PV. Thrombosis is a major cause of morbidity and mortality in PV; however, the characteristics of thrombosis in post-PV MF have not been characterised.

      Methods

      The clinical and laboratory characteristics of 163 patients with post-PV MF were analysed. Kaplan–Meier and multivariate Cox analyses were used to estimate risk factors for thrombosis.

      Results

      During follow-up, 84 (51.5%) patients developed thrombosis, 11 (6.7%) progressed to acute leukemia, 35 (21.5%) died (20% due to thrombosis). Thrombosis-free survival (TFS) in post-PV MF was lower than that of sex- and age-matched patients with PV (P < 0.0001). The incidence of venous thrombosis was significantly higher after diagnosis of post-PV MF than before or at diagnosis; Those with V617F% ≥ 75% or absolute monocyte count (AMC) ≥1.5 × 109/L demonstrated a higher risk for venous thrombosis (P < 0.05). According to multivariate Cox regression, palpable splenomegaly (hazard ratio [HR] 3.284 [95% confidence interval (CI) 1.373–7.855]; P = 0.008), age ≥ 60 years (HR 1.604 [95%CI 1.004–2.56]; P = 0.048), history of thrombosis (HR 2.767 [95%CI 1.735–4.412]; P < 0.001) were risk factors for thrombosis. In multivariable models, median TFS in post-PV MF in extremely high -, high -, intermediate -, low-risk groups were 2, 4, 9 and 13 years, respectively.

      Conclusion

      Patients with post-PV MF demonstrated a higher incidence of thrombosis. Palpable splenomegaly, age ≥ 60 years, history of thrombosis were independent risk factors for thrombosis.

      Keywords

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      References

        • Barbui T.
        • Barosi G.
        • Birgegard G.
        • et al.
        Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from european LeukemiaNet.
        J. Clin. Oncol. 2011; 29: 761-770https://doi.org/10.1200/jco.2010.31.8436
        • Barbui T.
        • Thiele J.
        • Gisslinger H.
        • et al.
        The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion.
        Blood Cancer J. 2018; 8: 15https://doi.org/10.1038/s41408-018-0054-y
        • Bai J.
        • Ai L.
        • Zhang L.
        • Yang F.C.
        • Zhou Y.
        • Xue Y.
        Incidence and risk factors for myelofibrotic transformation among 272 Chinese patients with JAK2-mutated polycythemia vera.
        Am. J. Hematol. 2015; 90: 1116-1121https://doi.org/10.1002/ajh.24191
        • Cerquozzi S.
        • Barraco D.
        • Lasho T.
        • et al.
        Risk factors for arterial versus venous thrombosis in polycythemia vera: a single center experience in 587 patients.
        Blood Cancer J. 2017; 7: 662https://doi.org/10.1038/s41408-017-0035-6
        • Tefferi A.
        • Rumi E.
        • Finazzi G.
        • et al.
        Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study.
        Leukemia. 2013; 27: 1874-1881https://doi.org/10.1038/leu.2013.163
        • Marchioli R.
        • Finazzi G.
        • Landolfi R.
        • et al.
        Vascular and neoplastic risk in a large cohort of patients with polycythemia vera.
        J. Clin. Oncol. 2005; 23: 2224-2232https://doi.org/10.1200/jco.2005.07.062
        • Mesa R.A.
        • Verstovsek S.
        • Cervantes F.
        • et al.
        Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), post essential thrombocythemia myelofibrosis (post-ET MF), blast phase PMF (PMF-BP): consensus on terminology by the international working group for myelofibrosis research and treatment (IWG-MRT).
        Leuk. Res. 2007; 31: 737-740https://doi.org/10.1016/j.leukres.2006.12.002
        • Passamonti F.
        • Giorgino T.
        • Mora B.
        • et al.
        A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis.
        Leukemia. 2017; 31: 2726-2731https://doi.org/10.1038/leu.2017.169
        • Passamonti F.
        • Rumi E.
        • Caramella M.
        • et al.
        A dynamic prognostic model to predict survival in post-polycythemia vera myelofibrosis.
        Blood. 2008; 111: 3383-3387https://doi.org/10.1182/blood-2007-11-121434
        • Bai J.
        • Shi H.
        • Ai L.
        • et al.
        Survival and prognosis of patients with polycythemia vera: a study of 816 patients in a single Chinese center.
        Zhonghua Yi Xue Za Zhi. 2015; 95: 1364-1368
        • Zhang Y.
        • Zhou Y.
        • Wang Y.
        • et al.
        Thrombosis among 1537 patients with JAK2(V617F) -mutated myeloproliferative neoplasms: risk factors and development of a predictive model.
        Cancer Med. 2020; 9: 2096-2105https://doi.org/10.1002/cam4.2886
        • Arber D.A.
        • Orazi A.
        • Hasserjian R.
        • et al.
        The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.
        Blood. 2016; 127 (Blood.128(3)(2016): 462-463): 2391-2405https://doi.org/10.1182/blood-2016-06-721662
        • Rungjirajittranon T.
        • Owattanapanich W.
        • Ungprasert P.
        • Siritanaratkul N.
        • Ruchutrakool T.
        A systematic review and meta-analysis of the prevalence of thrombosis and bleeding at diagnosis of Philadelphia-negative myeloproliferative neoplasms.
        BMC Cancer. 2019; 19: 184https://doi.org/10.1186/s12885-019-5387-9
        • Kaifie A.
        • Kirschner M.
        • Wolf D.
        • et al.
        Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry.
        J. Hematol. Oncol. 2016; 18 (9)https://doi.org/10.1186/s13045-016-0242-9
        • Jaipersad A.S.
        • Lip G.Y.
        • Silverman S.
        • Shantsila E.
        The role of monocytes in angiogenesis and atherosclerosis.
        J. Am. Coll. Cardiol. 2014; 63: 1-11https://doi.org/10.1016/j.jacc.2013.09.019
        • Rezende S.M.
        • Lijfering W.M.
        • Rosendaal F.R.
        • Cannegieter S.C.
        Hematologic variables and venous thrombosis: red cell distribution width and blood monocyte count are associated with an increased risk.
        Haematologica. 2014; 99: 194-200https://doi.org/10.3324/haematol.2013.083840
        • Laurance S.
        • Bertin F.R.
        • Ebrahimian T.
        • et al.
        Gas6 promotes inflammatory (CCR2(hi)CX3CR1(lo)) monocyte recruitment in venous thrombosis.
        Arterioscler. Thromb. Vasc. Biol. 2017; 37: 1315-1322https://doi.org/10.1161/atvbaha.116.308925
        • Borowczyk M.
        • Wojtaszewska M.
        • Lewandowski K.
        • et al.
        The JAK2 V617F mutational status and allele burden may be related with the risk of venous thromboembolic events in patients with Philadelphia-negative myeloproliferative neoplasms.
        Thromb. Res. 2015; 135: 272-280https://doi.org/10.1016/j.thromres.2014.11.006
        • Jaiswal S.
        • Natarajan P.
        • Silver A.J.
        • et al.
        Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease.
        N. Engl. J. Med. 2017; 377: 111-121https://doi.org/10.1056/NEJMoa1701719
        • Segura-Díaz A.
        • Stuckey R.
        • Florido Y.
        • et al.
        Thrombotic risk detection in patients with polycythemia vera: the predictive role of DNMT3A/TET2/ASXL1 mutations.
        Cancers (Basel). 2020; 12https://doi.org/10.3390/cancers12040934
        • Han X.
        • Bai B.B.
        • Wang C.J.
        • Zhao S.
        • Chen Y.
        Risk factors for recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia.
        Zhonghua Xue Ye Xue Za Zhi. 2019; 40: 17-23https://doi.org/10.3760/cma.j.issn.0253-2727.2019.01.004