Risk Stratification, Staging, and Treatment of Patients with Polycythemia Vera: Italian and European Collaboration on Low-Dose Aspirin in Polycythemia Data

ABSTRACT

The clinical course of polycythemia vera (PV) is marked by a high incidence of thrombotic complications, which represent the main cause of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use increases the risk of transformation into acute leukemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin based on the results of the European Collaboration on Low-Dose Aspirin in Polycythemia study. Cytotoxic therapy is indicated in high-risk patients, and the drug of choice is hydroxyurea because its leukemogenicity is low. New therapeutic options, that theoretically are devoid of leukemic risk (such as interferon α and imatinib), should be reserved for selected patients and require additional clinical experience.

Polycythemia vera - thrombosis - hydroxyurea - aspirin

REFERENCES

• 1 Finazzi G, Barbui T. Risk-adapted therapy in essential thrombocythemia and polycythemia vera.  Blood Rev. 2005;  19 243-252
• 2 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
• 3 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 2224-2232
• 4 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
• 5 Berk P D, Goldberg J D, Donovan P B, Fruchtman S M, Berlin N I, Wasserman L R. Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols.  Semin Hematol. 1986;  23 132-143
• 6 Gruppo Italiano Studio Policitemia (GISP) . Polycythemia vera: the natural history of 1213 patients followed over 20 years.  Ann Intern Med. 1995;  123 656-664
• 7 Najean Y, Rain J-D. The very long term evolution of polycythemia vera: an analysis of 318 patients initially treated by phlebotomy or 32P between 1969 and 1981.  Semin Hematol. 1997;  34 6-16
• 8 Haanen C, Mathé G, Hayat M. Treatment of polycythemia vera by radiophosphorus or busulphan. A randomizesd clinical trial.  Br J Cancer. 1981;  44 75-80
• 9 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
• 10 Najean Y. Rain JD 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
• 11 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
• 12 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
• 13 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
• 14 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
• 15 Shibata K, Shimamoto Y, Suga K et al.. Essential thrombocythemia terminating in acute leukemia with minimal myeloid differentiation-a brief review of recent literature.  Acta Haematol. 1994;  91 84-88
• 16 Silver R T. Interferon alpha2b: a new treatment for polycythemia vera.  Ann Intern Med. 1993;  119 1091-1092
• 17 Lengfelder E, Berger U, Hehlmann R. Interferon alpha in the treatment of polycythemia vera.  Ann Hematol. 2000;  79 103-109
• 18 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
• 19 Gilbert H S. Long term treatment of myeloproliferative disease with interferon alpha-2b: feasibility and efficacy.  Cancer. 1998;  83 1205-1213
• 20 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
• 21 Gruppo Italiano Studio Policitemia Vera . Feasibility of a randomised clinical trial with low-dose aspirin in polycythemia vera.  Br J Haematol. 1997;  97 453-456
• 22 van Genderen P J, Michiels J J. Erythromelalgic, thrombotic and hemorrhagic manifestations of thrombocythaemia.  Presse Med. 1994;  23 73-77
• 23 Van Genderen P JJ, Prins F, Michiels J J, Schrör K. Thromboxane-dependent platelet activation in vivo precedes arterial thrombosis in thrombocythaemia: a rationale for the use of low-dose aspirin as an antithrombotic agent.  Br J Haematol. 1999;  104 438-441
• 24 Koudstaal P, Koudstaal A. Neurologic and visual symptoms in essential thrombocythemia: efficacy of low-dose aspirin.  Semin Thromb Hemost. 1997;  23 365-370
• 25 Jabaily J, Iland H J, Laszlo J et al.. Neurologic manifestations of essential thrombocythemia.  Ann Intern Med. 1983;  99 513-518
• 26 Michiels J J, Koudstaal P, Mulder A H, van Vliet H HDM. Transient neurologic and ocular manifestations in primary thombocythemia.  Neurology. 1993;  43 1107-1110
• 27 Michiels J J, Van Genderen P JJ, Janssen P HP, Koudstaal P. Atypical transient ischemic attacks in thrombocythemia of various myeloproliferative disorders.  Leuk Lymphoma. 1996;  22(suppl 1) 65-70
• 28 Martyre M C. Critical review of pathogenetic mechanisms in myelofibrosis with myeloid metaplasia.  Curr Hematol Rep. 2003;  2 257-263
• 29 Silver R T, Fruchtman S M, Feldman E J, Spivak J L, Salvado A J. Imatinib mesylate (Gleevec) is effective in the treatment of polycythemia vera: a multi-institutional clinical trial.  Blood. 2004;  104 189 , (abst)