Abstract
Major causes of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET) are represented by thrombosis and bleeding, progression to myelofibrosis, and transformation to acute leukemia. Myelosuppressive therapy, preferentially with hydroxyurea, can reduce the rate of vascular complications, but there is some concern about an increased rate of leukemic transformation with this agent. Therefore, management of these disorders poses a significant challenge, and a risk-oriented therapeutic approach should be followed to avoid inappropriate exposure to cytotoxic drugs on one side or suboptimal treatment on the other. Established risk factors for cardiovascular events are represented by older age and previous thrombosis, while impact of novel biological factors, including leukocytosis and JAK2V617F mutational status and/or mutational burden, is under investigation. Low-risk PV patients should be managed only with phlebotomy and aspirin, while high-risk patients should also receive cytotoxic therapy. Regarding the management of ET, there is no clear indication for intervention in low-risk patients, while high-risk patients should be managed with chemotherapy. Other therapeutic options, such as interferon alpha or anagrelide, may find place in selected patients including those who are resistant/intolerant to hydroxyurea.
Keywords
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
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
McMullin MF, Bareford D, Campbell P, et al. Guidelines for the diagnosis, investigation and management of polycythemia/erythrocytosis. Br J Haematol 2005; 130: 174–195
Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 2005; 353: 33–45
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
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
Finazzi G, Barbui T. Evidence and expertise in the management of polycythemia vera and essential thrombocythemia. Leukemia 2008; 22: 1494–1502
Carobbio A, Finazzi G, Antonioli Aet al., Thrombocytosis and leukocytosis interaction in vascular complications of essential thrombocythemia. Blood 2008; 112: 3135–3137
Barbui T, Carobbio A, Rambaldi A, Finazzi G. Perspectives on thrombosis in essential thrombocythemia and polycythemia vera: is leukocytosis a causative factor? Blood 2009; 114: 759–763
Kundranda MN, Maiti B, Iqbal Net al., The association of leukocytosis, thrombocytosis and JAK2V617F mutation with thrombotic events in myeloproliferative disorders (MPD’s). Blood 2008; 112: abstr. 2803
Gangat N, Wolanskyj AP, Schwager SMet al., Leukocytosis at diagnosis and the risk of subsequent thrombosis in patients with low-risk essential thrombocythemia and polycythemia vera. Cancer 2009; 115: 5740–5745
Passamonti F, Rumi E, Pascutto C, et al. Increase in leukocyte count over time predicts thrombosis in patients with low-risk essential thrombocythemia. J Thromb Haemost 2009; 7: 1587–1589
Vannucchi AM, Antonioli E, Guglielmelli Pet al., Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia 2008; 22: 1299–1307
Lussana F, Caberlon S, Pagani Cet al., Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythemia or idiopathic myelofibrosis: a systematic review. Thromb Res 2009; 124: 409–417
De Stefano V, Za T, Rossi Eet al., Increased risk of recurrent thrombosis in patients with essential thrombocythemia carrying the homozygous JAK2 V617F mutation. Ann Hematol 2010; 89: 141–146
Vannucchi AM, Antonioli E, Guglielmelli Pet al., Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia. Blood 2008; 112: 844–847
Beer PA, Campbell PJ, Scott LMet al., MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood 2008; 112: 141–149
Campbell PJ, Bareford D, Erber WNet al., Reticulin accumulation in essential thrombocythemia: prognostic significance and relationship to therapy. J Clin Oncol 2009; 27: 2991–2999
Berk PD, Goldberg JD, Donovan PB, et al. Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. Semin Hematol 1986; 23: 132–143
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
Pearson TC, Wetherley-Mein G. Vascular occlusive episodes and venous haematocrit in primary proliferative polycythaemia. Lancet 1978; 2: 1219–1222
Di Nisio M, Barbui T, Di Gennaro L, et al. The hematocrit and platelet target in polycythemia vera. Br J Haematol 2007; 136: 249–259
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
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
Kiladjian JJ, Chevret S, Dosquet Cet al., Long-term outcome in polycythemia vera: final analysis of a randomized trial comparing hydroxyurea (HU) to pipobroman (Pi). Blood 2008; 112: abstr. 1746
Maugeri N, Giordano G, Petrilli MPet al., Inhibition of tissue factor expression by hydroxyurea in polimorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug? J Thromb Haemost 2006; 4: 2593–2598
Bjorkholm J, Derolf AR, Ekstrand Cet al., Clinical risk for AML/MDS transformation in Philadelphia negative chronic myeloproliferative neoplasms. A population-based nested case-control study in Sweden. 14th Congress European Hematology Association, Berlin June 4–7, 2009; abstr. 1085
Lanzkron S, Strouse JJ, Wilson Ret al., Systematic review: hydroxyurea for the treatment of adults with sickle cell disease. Ann Intern Med 2008; 148: 939–955
Barosi G, Besses C, Birgegard Get 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
Lengfelder E, Berger U, Hehlmann R. Interferon alpha in the treatment of polycythemia vera. Ann Hematol 2000; 79: 103–109
Silver RT. Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha. Cancer 2006; 107: 451–458
Lengfelder E, Griesshammer M, Hehlmann R. Interferon-alpha in the treatment of essential thrombocythemia. Leuk Lymphoma 1996; 22 (Suppl.1): 135–142
Kiladjian JJ, 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
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
Kiladjian JJ, Cassinat B, Chevret Set al., Pegylated interferon alpha-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 2008; 112: 3065–3072
Quintas-Cardama A, Kantarjian H, Manshouri Tet al., Pegylated interferon alpha-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 2009; 27: 5418–5424
Fruchtman SM, Petitt RM, Gilbert HS, et al. Anagrelide: analysis of long term efficacy, safety and leukemogenic potential in myeloproliferative diseases. Leuk Res 2005; 5: 481–491
Campbell PJ, Scott LM, 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
Gisslinger H, Gotic M, Holowiecki Jet al., Final results of the ANAHYDRET study: non-inferiority of anagrelide compared to hydroxyurea in newly diagnosed WHO essential thrombocythemia patients. Blood 2008; 112: abstr. 661
Barosi G, Birgegard G, Finazzi Get al., Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood 2009; 113: 4829–4833
Gangat N, Wolanskyj AP, Schwager S, Tefferi A. Predictors of pregnancy outcome in essential thrombocythemia: a single institution study of 63 pregnancies. Eur J Haematol 2009; 82: 350–353
Passamonti F, Randi ML, Rumi Eet al., Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V>F) mutation. Blood 2007; 110: 485–489
Griesshammer M, Struve S, Harrison CM. Essential thrombocythemia/polycythemia vera and pregnancy: the need for an observational study in Europe. Semin Thromb Hemost 2006; 32: 422–429
Tefferi A, Passamonti F. Essential thrombocyythemia and pregnancy: observations from recent studies and management recommenadtions. Am J Hematol 2009; 84: 629–630
Barbui T, Finazzi G. Myeloproliferative disease in pregnancy and other management issues. Hematology Am Soc Hematol Educ Program 2006; 246–252
Martinelli I, Franchini M, Mannucci PM. How I treat rare venous thrombosis. Blood 2008; 112: 4818–4823
Condat B, Pessione F, Hillaire Set al., Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy. Gastroenterology 2001; 120: 490–497
Kiladjian JJ, Cervantes F, Leebek FWGet al., The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood 2008; 111: 4922–4929
Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 2004; 128: 275–290
Ruggeri M, Rodeghiero F, Tosetto Aet al., Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey. Blood 2008; 111: 666–671
Tefferi A, Mesa RA, Nagorney DM, Schroeder G, Silverstein MN. Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood 2000; 95: 226–233
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Finazzi, G., Barbui, T. (2011). Therapy of Polycythemia Vera and Essential Thrombocythemia. In: Verstovsek, S., Tefferi, A. (eds) Myeloproliferative Neoplasms. Contemporary Hematology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-266-7_5
Download citation
DOI: https://doi.org/10.1007/978-1-60761-266-7_5
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-265-0
Online ISBN: 978-1-60761-266-7
eBook Packages: MedicineMedicine (R0)