Polycythemia Vera Overview

Polycythemia vera (PV), myelofibrosis and essential thrombocythemia are classified as Philadelphia chromosome-negative myeloproliferative neoplasms.1 PV is characterized by clonal stem cell proliferation of the erythroid, myeloid and megakaryocytic lines while its predominant characteristic is an increase in red blood cell mass, increased white blood cell and platelet counts are common.2,3

Polycythemia Vera (PV) is a myeloproliferative neoplasm (MPN), most often associated with the JAK2V617F point mutation that results in overactive signaling through the JAK-STAT pathway.4-6 PV is characterized by hyperproliferation of red blood cells (erythrocytosis) and significant symptom burden. 5-9 The increase in red blood cell mass results in hyperviscosity of the blood, increased thrombotic risk, significant morbidity and a shortened life expectancy.10 Advanced PV is frequently characterized by palpable splenomegaly and severe constitutional symptoms, including fatigue (85%), pruritus (65%), night sweats (49%) and bone pain (43%).11

The current therapeutic approach in PV focuses on lowering the risk for thrombotic events without exposing patients to increased risk of leukemic transformation.12 While phlebotomy and low-dose aspirin are accepted as the standard of care for initial therapy, cytoreductive therapy is recommended to aid in the control of erythrocytosis in the presence of poor tolerance to phlebotomy, symptomatic or progressive splenomegaly or evidence of high thrombotic risk. Hydroxyurea (HU) is frequently the cytoreductive agent of choice and therapeutic options beyond HU are limited.3,12

References

  • Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008;22:14-22.

  • Spivak JL. Polycythemia vera: myths, mechanisms, and management. Blood. 2002;100:4272-4290.

  • Polycythemia vera. The Leukemia and Lymphoma Society Web site.
    http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/polycythemiavera.pdf. Published May 2007. Accessed June 4, 2012.

  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation.Cell. 2011;144:646-674.

  • Spivak JL.Narrative review: Thrombocytosis, polycythemia vera, and JAK2 mutations: The phenotypic mimicry of chronic myeloproliferation. Ann Intern Med. 2010;152:300-306.

  • Furqan M, Mukhi N, Lee B, Liu D. Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application. Biomarker Res. 2013;1:1-10.

  • Vannucchi AM, Guglielmelli P, Tefferi A.Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin. 2009;59:171-191.

  • Marchioli R, Finazzi G, Specchia G, et al; for the CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368:22-33.

  • Tefferi A. Polycythemia vera and essential thrombocythemia: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013;88:507-516.

  • Kumar C, Purandare AV, Lee FY, Lorenzi MV. Kinase drug discovery approaches in chronic myeloproliferative disorders. Oncogene. 2009;28:2305-2313.

  • Mesa RA, Niblack J, Wadleigh M, et al. The burden of fatigue and quality of life in myeloproliferative disorders (MPDs): an international Internet-based survey of 1179 MPD patients. Cancer. 2007;109:68-76.

  • Finazzi G, Barbui T. Evidence and expertise in the management of polycythemia vera and essential thrombocythemia.Leukemia . 2008;22:1494-1502.