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Essential thrombocythemia: a review of the clinical features, diagnostic challenges, and treatment modalities in the era of molecular discovery

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Pages 2786-2798 | Received 08 Nov 2016, Accepted 15 Mar 2017, Published online: 15 May 2017

References

  • Ma X, Vanasse G, Cartmel B, et al. Prevalence of polycythemia vera and essential thrombocythemia. Am J Hematol. 2008;83:359–362.
  • Mesa RA, Silverstein MN, Jacobsen SJ, et al. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted county study, 1976–1995. Am J Hematol. 1999;61:10–15.
  • 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.
  • Fenaux P, Simon M, Caulier MT, et al. Clinical course of essential thrombocythemia in 147 cases. Cancer. 1990;66:549–556.
  • Tefferi A, Fonseca R, Pereira DL, et al. A long-term retrospective study of young women with essential thrombocythemia. Mayo Clin Proc. 2001;76:22–28.
  • Epstein E, Goedel A. Hämorrhagische thrombocythämie bei vasculärer schrumpfmilz. Virchows Arch path Anat. 1934;292:233–248.
  • Fanger H, Cella LJ, Jr, Litchman H. Thrombocythemia; report of three cases and review of literature. N Engl J Med. 1954;250:456–461.
  • Ozer FL, Truax WE, Miesch DC, et al. Symposium on leukemia primary hemorrhagic thrombocythemia. Am J Med. 1960;28:807–823.
  • Murphy SI, H, Rosenthal D, Laszlo J. Essential thrombocythemia: an interim report from the polycythemia vera study group. Semin Hematol. 1986;23:177–182.
  • Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:1054–1061.
  • Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387–397.
  • James C, Ugo V, Le Couedic J-P, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434:1144–1148.
  • Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779–1790.
  • Pardanani AD, Levine RL, Lasho T, et al. Mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood. 2006;108:3472–3476.
  • Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3:e270.
  • Cazzola M, Kralovics R. From Janus kinase 2 to calreticulin: the clinically relevant genomic landscape of myeloproliferative neoplasms. Blood. 2014;123:3714–3719.
  • Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369:2379–2390.
  • Tefferi A, Guglielmelli P, Larson DR, et al. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014;124:2507–2513.
  • Adamson JW, Fialkow PJ, Murphy S, et al. Polycythemia vera: stem-cell and probable clonal origin of the disease. N Engl J Med. 1976;295:913–916.
  • Fialkow PJ, Faguet GB, Jacobson RJ, et al. Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell. Blood. 1981;58:916–919.
  • Gaetani GF, Ferraris AM, Galiano S, et al. Primary thrombocythemia: clonal origin of platelets, erythrocytes, and granulocytes in a GdB/GdMediterranean subject. Blood. 1982;59:76–79.
  • Dai CH, Krantz SB, Dessypris EN, et al. Polycythemia vera. II. Hypersensitivity of bone marrow erythroid, granulocyte-macrophage, and megakaryocyte progenitor cells to interleukin-3 and granulocyte-macrophage colony-stimulating factor. Blood. 1992;80:891–899.
  • Li Y, Hetet G, Maurer A-M, et al. Spontaneous megakaryocyte colony formation in myeloproliferative disorders is not neutralizable by antibodies against IL3, IL6 and GM-CSF. Br J Haematol. 1994;87:471–476.
  • Kobayashi S, Teramura M, Hoshino S, et al. Circulating megakaryocyte progenitors in myeloproliferative disorders are hypersensitive to interleukin-3. Br J Haematol. 1993;83:539–544.
  • Axelrad AA, Eskinazi D, Correa PN, et al. Hypersensitivity of circulating progenitor cells to megakaryocyte growth and development factor (PEG-rHu MGDF) in essential thrombocythemia. Blood. 2000;96:3310–3321.
  • Tortolani PJ, Johnston JA, Bacon CM, et al. Thrombopoietin induces tyrosine phosphorylation and activation of the Janus kinase, JAK2. Blood. 1995;85:3444–3451.
  • Marty C, Pecquet C, Nivarthi H, et al. Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis. Blood. 2016;127:1317–1324.
  • Chachoua I, Pecquet C, El-Khoury M, et al. Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants. Blood. 2016;127:1325–1335.
  • Araki M, Yang Y, Masubuchi N, et al. Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms. Blood. 2016;127:1307–1316.
  • Wolanskyj AP, Lasho TL, Schwager SM, et al. JAK2V617F mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol. 2005;131:208–213.
  • Kittur J, Knudson RA, Lasho TL, et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer. 2007;109:2279–2284.
  • Cheung B, Radia D, Pantelidis P, et al. The presence of the JAK2 V617F mutation is associated with a higher haemoglobin and increased risk of thrombosis in essential thrombocythaemia. Br J Haematol. 2006;132:244–245.
  • Zhang S, Qiu H, Fischer BS, et al. JAK2 V617F patients with essential thrombocythemia present with clinical features of polycythemia vera. Leuk Lymphoma. 2008;49:696–699.
  • Toyama K, Karasawa M, Yamane A, et al. JAK2-V617F mutation analysis of granulocytes and platelets from patients with chronic myeloproliferative disorders: advantage of studying platelets. Br J Haematol. 2007;139:64–69.
  • Wong RSM, Cheng C-K, Chan NPH, et al. JAK2 V617F mutation is associated with increased risk of thrombosis in Chinese patients with essential thrombocythaemia. Br J Haematol. 2008;141:902–904.
  • Campbell PJ, Scott LM, Buck G, et al. Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet. 2005;366:1945–1953.
  • Rumi E, Pietra D, Ferretti V, et al. CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood. 2014;123:1544–1551.
  • Rotunno G, Mannarelli C, Guglielmelli P, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood. 2014;123:1552–1555.
  • Pietra D, Rumi E, Ferretti VV, et al. Differential clinical effects of different mutation subtypes in CALR-mutant myeloproliferative neoplasms. Leukemia. 2016;30:431–438.
  • Cabagnols X, Favale F, Pasquier F, et al. Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients. Blood. 2016;127:333–342.
  • Milosevic Feenstra JD, Nivarthi H, Gisslinger H, et al. Sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms. Blood 2016;127:325–332.
  • Yamamoto Y, Iba S, Abe A, et al. Elongation of MPL transmembrane domain is a novel activating-mutation in essential thrombocythemia. Blood. 2015;126:1628–1628.
  • Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia. 2010;24:1128–1138.
  • Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369:2391–2405.
  • Tefferi A, Lasho TL, Finke C, et al. Targeted next-generation sequencing in polycythemia vera and essential thrombocythemia. Blood. 2015;126:354–354.
  • Tefferi A, Lasho TL, Guglielmelli P, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv. 2016;1:21–30.
  • Gangat N, Tefferi A, Thanarajasingam G, et al. Cytogenetic abnormalities in essential thrombocythemia: prevalence and prognostic significance. Eur J Haematol. 2009;83:17–21.
  • Sessarego M, Defferrari R, Dejana AM, et al. Cytogenetic analysis in essential thrombocythemia at diagnosis and at transformation. A 12-year study. Cancer Genet Cytogenet. 1989;43:57–65.
  • Panani AD. Cytogenetic findings in untreated patients with essential thrombocythemia. In Vivo. 2006;20:381–384.
  • Suleiman Y, Dalia S, Liu JJ, et al. Clinical prognostic factors and outcomes of essential thrombocythemia when transformed to myelodysplastic syndromes and acute myeloid leukemia. Leukemia Res. 2016;42:52–58.
  • Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–2405.
  • Barbui T, Thiele J, Passamonti F, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011;29:3179–3184.
  • Thiele J, Kvasnicka HM. Chronic myeloproliferative disorders with thrombocythemia: a comparative study of two classification systems (PVSG, WHO) on 839 patients. Ann Hematol. 2003;82:148–152.
  • Thiele J, Kvasnicka HM, Schmitt-Graeff A, et al. Follow-up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): a retrospective clinicopathological study of 120 patients. Am J Hematol. 2002;70:283–291.
  • Thiele J, Kvasnicka HM, Müllauer L, et al. Essential thrombocythemia versus early primary myelofibrosis: a multicenter study to validate the WHO classification. Blood. 2011;117:5710–5718.
  • Gisslinger H, Jeryczynski G, Gisslinger B, et al. Clinical impact of bone marrow morphology for the diagnosis of essential thrombocythemia: comparison between the BCSH and the WHO criteria. Leukemia. 2016;30:1126–1132.
  • Carobbio A, Thiele J, Passamonti F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood. 2011;117:5857–5859.
  • Barbui T, Finazzi G, Carobbio A, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization–essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120:5128–5133.
  • Haider M, Gangat N, Lasho T, et al. Validation of the revised international prognostic score of thrombosis for essential thrombocythemia (IPSET-thrombosis) in 585 Mayo clinic patients. Am J Hematol. 2016;91:390–394.
  • Passamonti F, Rumi E, Arcaini L, et al. Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients. Haematologica. 2008;93:1645–1651.
  • Gangat N, Wolanskyj AP, McClure RF, et al. Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients. Leukemia. 2006;21:270–276.
  • Abdulkarim K, Ridell B, Johansson P, et al. The impact of peripheral blood values and bone marrow findings on prognosis for patients with essential thrombocythemia and polycythemia vera. Eur J Haematol. 2011;86:148–155.
  • Chim C, Kwong Y, Lie A, et al. Long-term outcome of 231 patients with essential thrombocythemia: prognostic factors for thrombosis, bleeding, myelofibrosis, and leukemia. Arch Intern Med. 2005;165:2651–2658.
  • Barosi G, Mesa RA, Thiele J, et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the international working group for myelofibrosis research and treatment. Leukemia. 2007;22:437–438.
  • Thiele J, Kvasnicka HM, Facchetti F, et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90:1128–1132.
  • Manoharan A, Horsley R, Pitney WR. The reticulin content of bone marrow in acute leukaemia in adults. Br J Haematol. 1979;43:185–190.
  • Cervantes F, Alvarez-Larrán A, Talarn C, et al. Myelofibrosis with myeloid metaplasia following essential thrombocythaemia: actuarial probability, presenting characteristics and evolution in a series of 195 patients. Br J Haematol. 2002;118:786–790.
  • Alvarez-Larran A, Cervantes F, Bellosillo B, et al. Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients. Leukemia. 2007;21:1218–1223.
  • Wolanskyj AP, Schwager SM, McClure RF, et al. Essential thrombocythemia beyond the first decade: life expectancy, long-term complication rates, and prognostic factors. Mayo Clin Proc. 2006;81:159–166.
  • Beer PA, Campbell PJ, Scott LM, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood. 2008;112:141–149.
  • Stein BL, Williams DM, O’Keefe C, et al. of the ASXL1 gene is frequent in primary, post-essential thrombocytosis and post-polycythemia vera myelofibrosis, but not essential thrombocytosis or polycythemia vera: analysis of molecular genetics and clinical phenotypes. Haematologica. 2011;96:1462–1469.
  • Passamonti F, Rumi E, Pungolino E, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med. 2004;117:755–761.
  • Rozman CE, F, Giralt M, Rubio D, et al. Life expectancy of patients with chronic nonleukemic myeloproliferative disorders. Cancer. 1991;67:2658–2663.
  • Passamonti F, Thiele J, Girodon F, et al. A prognostic model to predict survival in 867 World Health Organization–defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment. Blood. 2012;120:1197–1201.
  • 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;29:761–770.
  • Rumi E, Cazzola M. How we treat essential thrombocythemia. Blood. 2016;128:2403–2414.
  • Besses CC, F, Pereira A, Florensa L, et al. Major vascular complications in essential thrombocythemia: a study of the predictive factors in a series of 148 patients. Leukemia. 1999;13:150–154.
  • Budde UvG PJ. Acquired von Willebrand disease in patients with high platelet counts. Semin Thromb Hemost. 1997;23:425–431.
  • 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.
  • Dueck AC, Geyer HL, Kiladjian J-J, et al. Myeloproliferative (MPN) symptom burden response thresholds: assessment of MPN-SAF TSS quartiles as potential markers of symptom response. Blood. 2013;122:4067–4067.
  • Johansson P, Mesa R, Scherber R, et al. Association between quality of life and clinical parameters in patients with myeloproliferative neoplasms. Leuk Lymphoma. 2012;53:441–444.
  • Geyer HL, Mesa RA. Therapy for myeloproliferative neoplasms: when, which agent, and how? ASH Educ Prog Book. 2014;2014:277–286.
  • 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.
  • Alvarez-Larrán A, Pereira A, Guglielmelli P, et al. Antiplatelet therapy versus observation in low-risk essential thrombocythemia with CALR mutation. Haematologica. 2016;101:926–931.
  • Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med. 1995;332:1132–1137.
  • 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.
  • Gisslinger H, Gotic M, Holowiecki J, et al. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013;121:1720–1728.
  • Mela Osorio MJ, Ferrari L, Goette NP, et al. Long-term follow-up of essential thrombocythemia patients treated with anagrelide: subgroup analysis according to JAK2/CALR/MPL mutational status. Eur J Haematol. 2016;96:435–442.
  • Quintás-Cardama A, Abdel-Wahab O, Manshouri T, et al. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. Blood. 2013;122:893–901.
  • Verger E, Cassinat B, Chauveau A, et al. Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations. Blood. 2015;126:2585–2591.
  • Gowin K, Thapaliya P, Samuelson J, et al. Experience with pegylated interferon α-2a in advanced myeloproliferative neoplasms in an international cohort of 118 patients. Haematologica. 2012;97:1570–1573.
  • Stauffer Larsen T, Iversen KF, Hansen E, et al. Long term molecular responses in a cohort of Danish patients with essential thrombocythemia, polycythemia vera and myelofibrosis treated with recombinant interferon alpha. Leukemia Res. 2013;37:1041–1045.
  • Appelmann I, Kreher S, Parmentier S, et al. Diagnosis, prevention, and management of bleeding episodes in Philadelphia-negative myeloproliferative neoplasms: recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO) and the Society of Thrombosis and Hemostasis Research (GTH). Ann Hematol. 2016;95:707–718.
  • Kander EM, Raza S, Zhou Z, et al. Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort. Int J Hematol. 2015;102:587–593.
  • Finazzi G, Carobbio A, Thiele J, et al. Incidence and risk factors for bleeding in 1104 patients with essential thrombocythemia or prefibrotic myelofibrosis diagnosed according to the 2008 WHO criteria. Leukemia. 2012;26:716–719.
  • Alvarez-Larrán A, Cervantes F, Pereira A, et al. Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood. 2010;116:1205–1210.
  • Michiels JJ, Van Genderen PJJ, Lindemans J, et al. Erythromelalgic, thrombotic and hemorrhagic manifestations in 50 cases of thrombocythemia. Leuk Lymphoma. 1996;22:47–56.
  • Papadakis E, Hoffman R, Brenner B. Thrombohemorrhagic complications of myeloproliferative disorders. Blood Rev. 2010;24:227–232.
  • Greist A. The role of blood component removal in essential and reactive thrombocytosis. Therapher Dial. 2002;6:36–44.
  • Agarwal MB, Malhotra H, Chakrabarti P, et al. Myeloproliferative neoplasms working group consensus recommendations for diagnosis and management of primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Indian J Med Paediatr Oncol. 2015;36:3–16.
  • Wright CA, Tefferi A. A single institutional experience with 43 pregnancies in essential thrombocythemia. Eur J Haematol. 2001;66:152–159.
  • Lavi N, Brenner B, Avivi I, Management of pregnant women with myeloproliferative neoplasms. Thromb Res. 2013;131:S11–S13.
  • Passamonti F, Randi ML, Rumi E, et al. Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V > F) mutation. Blood 2007;110:485–489.
  • Harrison CN, Robinson SE. Myeloproliferative disorders in pregnancy. Hematol Oncol Clin North Am. 2011;25:261–275.
  • Randi ML, Bertozzi I, Rumi E, et al. Pregnancy complications predict thrombotic events in young women with essential thrombocythemia. Am J Hematol. 2014;89:306–309.
  • Barbui T, Finazzi G. Myeloproliferative disease in pregnancy and other management issues. ASH Educ Prog Book. 2006;2006:246–252.
  • Alimam S, Bewley S, Chappell LC, et al. Pregnancy outcomes in myeloproliferative neoplasms: UK prospective cohort study. Br J Haematol. 2016;175:31–36.
  • Rumi E, Bertozzi I, Casetti IC, et al. Impact of mutational status on pregnancy outcome in patients with essential thrombocytemia. Haematologica. 2015;100:e443–e445.
  • Kreher S, Ochsenreither S, Trappe RU, et al. Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasms: consensus statement of the Haemostasis Working Party of the German Society of Hematology and Oncology (DGHO), the Austrian Society of Hematology and Oncology (ÖGHO) and Society of Thrombosis and Haemostasis Research (GTH e.V.). Ann Hematol. 2014;93:1953–1963.
  • Beauverd Y, Radia D, Cargo C, et al. Pegylated interferon alpha-2a for essential thrombocythaemia during pregnancy, outcome and safety: a case series. Haematologica. 2016;101:e182–e184.
  • Hinds DA, Barnholt KE, Mesa RA, et al. Germ line variants predispose to both JAK2 V617F clonal hematopoiesis and myeloproliferative neoplasms. Blood. 2016;128:1121–1128.
  • Rumi E, Passamonti F, Pietra D, et al. JAK2 (V617F) as an acquired somatic mutation and a secondary genetic event associated with disease progression in familial myeloproliferative disorders. Cancer. 2006;107:2206–2211.
  • Bellanné-Chantelot C, Chaumarel I, Labopin M, et al. Genetic and clinical implications of the Val617Phe JAK2 mutation in 72 families with myeloproliferative disorders. Blood. 2006;108:346–352.
  • Rumi E, Harutyunyan AS, Pietra D, et al. CALR exon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis. Blood. 2014;123:2416–2419.
  • Ding J, Komatsu H, Wakita A, et al. Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood. 2004;103:4198–4200.
  • Hultcrantz M, Lund SH, Landgren O, et al. Survival in patients with familial and sporadic myeloproliferative neoplasms. Blood. 2015;125:3665–3666.
  • Stein BL, O’Brien S, Greenberg P, et al. The need for United States–based guidelines for myeloproliferative neoplasms. J Natl Compr Canc Netw. 2015;13:607–609.
  • Baerlocher GM, Oppliger Leibundgut E, Ottmann OG, et al. Telomerase inhibitor imetelstat in patients with essential thrombocythemia. N Engl J Med. 2015;373:920–928.
  • Verstovsek S, Passamonti F, Rambaldi A, et al. Long-term results from a phase II open-label study of ruxolitinib in patients with essential thrombocythemia refractory to or intolerant of hydroxyurea. Blood. 2014;124:1847.

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