RSS-Feed abonnieren
DOI: 10.1055/s-2007-976166
Therapy for Polycythemia Vera and Essential Thrombocythemia Is Driven by the Cardiovascular Risk
Publikationsverlauf
Publikationsdatum:
24. Mai 2007 (online)
![](https://www.thieme-connect.de/media/sth/200704/lookinside/thumbnails/10.1055-s-2007-976166-1.jpg)
ABSTRACT
The clinical course of polycythemia vera (PV) and essential thrombocythemia (ET) is characterized by an increased incidence of thrombotic and hemorrhagic complications and an inherent tendency to progress into myelofibrosis or acute myeloid leukemia. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thromboses and hemorrhages, but there is concern that their use accelerates the rate of leukemic transformation. Thus, a risk-oriented management strategy is recommended. Low-risk patients with PV should be treated with phlebotomy and low-dose aspirin, whereas those with ET can be left untreated. Cytotoxic agents are recommended in high-risk cases and hydroxyurea is the drug of choice in most patients. Interferon alpha or anagrelide could be considered in selected young patients or as second-line therapy in those refractory or intolerant of hydroxyurea. The recent identification of JAK2V617F mutation in a substantial proportion of patients with PV and ET raises new questions regarding both risk classification and management, but additional studies on these issues are required.
KEYWORDS
Polycythemia vera - essential thrombocythemia - risk factors - thrombosis - hydroxyurea
REFERENCES
- 1 Marchioli R, Finazzi G, Landolfi R et al.. Morbidity and mortality of a multicountry prospective cohort of 1,638 patients with polycythemia vera. J Clin Oncol. 2005; 23 2224-2232
- 2 Berk P D, Goldberg J D, Donovan P B et al.. Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. Semin Hematol. 1986; 23 132-143
- 3 Landolfi R, Di Nisio M, Finazzi G et al.. Leukocytosis as a major risk factor in patients with polycythemia vera. Blood. 2006; November 14; , (Epub ahead of print)
- 4 Cortelazzo S, Viero P, Finazzi G et al.. Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol. 1990; 8 556-562
- 5 Barbui T, Barosi G, Grossi A et al.. Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation. Haematologica. 2004; 89 215-232
- 6 Harrison C N. Essential thrombocythaemia: challenges and evidence-based management. Br J Haematol. 2005; 130 153-165
- 7 Schafer A I. Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood. 2006; 107 4214-4222
- 8 Tefferi A, Elliot M. Thrombosis in myeloproliferative disorders: prevalence, prognostic factors, and the role of leukocytes and JAK2V617F. Semin Thromb Hemost. 2006; 33 313-320
- 9 Campbell P J, Scott L M, Buck G et al.. Definition of subtypes of essential thrombocythaemia and relation to polycythemia vera based on JAK2 V617F mutation status: a prospective study. Lancet. 2005; 366 1945-1953
- 10 Kralovics R, Passamonti F, Buser A S et al.. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005; 352 1779-1790
- 11 Cheung B, Radia D, Pantedelis P, Yadergarfar G, Harrison C. The presence of the JAK2 V617F mutation is associated with a higher haemoglobin and increased risk of thrombosis in essential thrombocythemia. Br J Haematol. 2005; 132 244-250
- 12 Antonioli E, Guglielmelli P, Pantelrolis A et al.. Clinical implications of the JAK2 V617F mutation in essential thrombocythemia. Leukemia. 2005; 19 1847-1849
- 13 Wolansky A P, Lasho T L, Schwager S M et al.. JAK2 V617F mutation in essential thrombocythemia: clinical associations and long-term prognostic relevance. Br J Haematol. 2005; 131 208-213
- 14 Finazzi G, Rambaldi A, Guerini V, Carobbio A, Barbui T. Risk of thrombosis in patients with essential thrombocythemia and polycythemia vera according to JAK2 V617F mutation. Haematologica. 2007; 92 135-136
- 15 Harrison C N, Campbell P J, Buck G et al.. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005; 353 33-45
- 16 Wolanskyj A P, Schwager S M, McClure R F, Larson D R, Tefferi A. Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors. Mayo Clin Proc. 2006; 81 159-166
- 17 Carobbio A, Finazzi G, Guerini V et al.. Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors and JAK2 mutation status. Blood. 2006; November 16; , (Epub ahead of print)
- 18 Arellano-Rodrigo E, Alvarez-Larran A, Reverter J C et al.. Increased platelet and leukocyte activation as contributing mechanisms for thrombosis in essential thrombocythemia and correlation with the JAK2 mutational status. Haematologica. 2006; 91 169-175
- 19 Falanga A, Marchetti M, Balducci D et al.. Distinct hemostatic profile of leukocytes in essential thrombocythemia carrying the JAK2 V617F mutation. Blood. 2005; 106 114 (abst)
- 20 Budde U, van Genderen P J. Acquired von Willebrand disease in patients with high platelet counts. Semin Thromb Hemost. 1997; 23 425-431
- 21 Tefferi A, Gangat N, Wolanskyj A P. Management of extreme thrombocytosis in otherwise low-risk essential thrombocythemia: does number matter?. Blood. 2006; 108 2493-2494
- 22 Ruggeri M, Finazzi G, Tosetto A et al.. No treatment for low-risk essential thrombocythemia: results from a prospective study. Br J Haematol. 1998; 103 772-777
- 23 Pearson T C, Wetherley-Mein G. Vascular occlusive episodes and venous haematocrit in primary proliferative polycythaemia. Lancet. 1978; 2 1219-1222
- 24 Di Nisio M, Landolfi R, Finazzi G et al.. How enough certain is the current therapeutic target of hematocrit in polycythemia vera?. Br J Haematol, Submitted.
- 25 Tartaglia A P, Goldberg J D, Berk P D, Wasserman L R. Adverse effects of antiaggregating platelet therapy in the treatment of polycythemia vera. Semin Hematol. 1986; 23 172-176
- 26 Streiff M B, Smith B, Spivak J L. The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of the American Society of Hematology members' practice patterns. Blood. 2002; 99 1144-1149
- 27 Patrono C, Garcia-Rodriguez L A, Landolfi R et al.. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005; 353 2373-2383
- 28 Landolfi R, Marchioli R, Kutti J et al.. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004; 350 114-124
- 29 Cortelazzo S, Finazzi G, Ruggeri M et al.. Hydroxyurea in the treatment of patients with essential thrombocythemia at high risk of thrombosis: a prospective randomized trial. N Engl J Med. 1995; 332 1132-1136
- 30 Fruchtman S M, Mack K, Kaplan M E et al.. From efficacy to safety: a polycythemia vera study group report on hydroxyurea in patients with polycythemia vera. Semin Hematol. 1997; 34 17-23
- 31 Najean Y, Rain J D. for the French Polycythemia Study Group . Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997; 90 3370-3377
- 32 Nand S, Stock W, Godwin J et al.. Leukemogenic risk of hydroxyurea therapy in polycythemia vera, essential thrombocythemia and myeloid metaplasia with myelofibrosis. Am J Hematol. 1996; 52 42-46
- 33 Sterkers Y, Preudhomme C, Lai J-L et al.. Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion. Blood. 1998; 91 616-622
- 34 Hanft V N, Fruchtman S R, Pickens C V et al.. Acquired DNA mutations associated with in vivo hydroxyurea exposure. Blood. 2000; 95 3589-3593
- 35 Finazzi G, Caruso V, Marchioli R et al.. Acute leukemia in polycythemia vera. An analysis of 1,638 patients enrolled in a prospective observational study. Blood. 2005; 105 2664-2670
- 36 Silver R T. Interferon alpha2b: a new treatment for polycythemia vera. Ann Intern Med. 1993; 119 1091-1092
- 37 Martyre M C. Critical review of pathogenetic mechanisms in myelofibrosis with myeloid metaplasia. Curr Hematol Rep. 2003; 2 257-263
- 38 Lengfelder E, Berger U, Hehlmann R. Interferon alpha in the treatment of polycythemia vera. Ann Hematol. 2000; 79 103-109
- 39 Heis N, Rintelen C, Gisslinger B et al.. The effect of interferon alpha on myeloproliferation and vascular complications in polycythemia vera. Eur J Haematol. 1999; 62 27-31
- 40 Gilbert H S. Long term treatment of myeloproliferative disease with interferon alpha-2b: feasibility and efficacy. Cancer. 1998; 83 1205-1213
- 41 Silver R T. Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha. Cancer. 2006; 107 451-458
- 42 Kiladjian J J, Cassinat B, Turlure P et al.. High molecular response rate of polycythemia vera patients treated with pegylated interferon alpha-2a. Blood. 2006; 108 2037-2040
- 43 Finazzi G, Ruggeri M, Rodeghiero F, Barbui T. Efficacy and safety of long-term use of hydroxyurea in young patients with essential thrombocythemia and a high risk of thrombosis. Blood. 2003; 101 3749
- 44 Finazzi G, Ruggeri M, Rodeghiero F et al.. Second malignancies in patients with essential thrombocythemia treated with busulphan and hydroxyurea: long-term follow-up of a randomized clinical trial. Br J Haematol. 2000; 110 577-583
- 45 Murphy S, Iland H, Rosenthal D et al.. Essential thrombocythemia: an interim report from the Polycythemia Vera Study Group. Semin Hematol. 1986; 23 177-182
- 46 Fruchtman S M, Petitt R M, Gilbert H S et al.. Anagrelide: analysis of long term efficacy, safety and leukemogenic potential in myeloproliferative diseases. Leuk Res. 2005; 29 481-491
- 47 Storen E C, Tefferi A. Long-term use of anagrelide in young patients with essential thrombocythemia. Blood. 2001; 97 863-866
- 48 Barbui T, Finazzi G. When and how to treat essential thrombocythemia. N Engl J Med. 2005; 353 85-86
- 49 Barosi G, Besses C, Birgegard G et al.. A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia: results of a consensus process by an International Working Group. Leukemia. 2007; 21 277-280
- 50 Lengfelder E, Griesshammer M, Hehlmann R. Interferon-alpha in the treatment of essential thrombocythemia. Leuk Lymphoma. 1996; 22(suppl 1) 135-142
- 51 Harrison C. Pregnancy and its management in the Philadelphia negative myeloproliferative diseases. Br J Haematol. 2005; 129 293-306
- 52 Silver R T, Fruchtman S M, Feldman E J et al.. Imatinib mesylate (Gleevec) is effective in the treatment of polycythemia vera: a multi-institutional clinical trial. Blood. 2004; 104 189 (abst)
- 53 Jones A V, Silver R T, Waghorn K et al.. Minimal molecular response in polycythemia vera patients treated with imatinib or with interferon alpha. Blood. 2006; 107 3339-3341
- 54 Samuelsson J, Mutschler M, Birgegard G et al.. Limited effects on JAK2 mutational status after pegylated interferon α-2b therapy in polycythemia vera and essential thrombocythemia. Haematologica. 2006; 91 1281-1282
Tiziano BarbuiM.D.
Department of Hematology-Oncology, Ospedali Riuniti
Largo Barozzi 1, 24128 Bergamo, Italy
eMail: tbarbui@ospedaliriuniti.bergamo.it