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  • 1 Somogy Megyei Kaposi Mór Oktató Kórház, 7400 Kaposvár, Tallián Gy. u. 20–32.
  • 2 Debreceni Egyetem, Általános Orvostudományi Kar, Debrecen
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Az essentialis thrombocythaemia Philadelphia-negatív krónikus myeloproliferatív neoplázia, amelyet emelkedett thrombocytaszám, megakaryocyta hyperplasia, fokozott thrombohaemorrhagiás és lassan progrediáló transzformációs hajlam jellemez. Ritka betegség, incidenciája 0,5–1,5/100 000 lakos/év, előfordulása női predominanciát és bimodalitást mutat: fiatal nőkben és az 50–70 évesekben gyakoribb. Az essentialis thrombocythaemia diagnózisa a 450·109/l feletti thrombocytaszámon, a normális erythroid sejttömegen és vasraktáron, valamint egyéb thrombocytosist okozó tényezők hiányán alapul, egyéb myeloproliferativ neoplasiák (a myelofibrosis, krónikus myeloid leukémia) kizárandóak. A Janus-2 pszeudokináz gén V617F-mutációja az essentialis thrombocythaemiás esetek közel 50%-ában fordul elő, a fennmaradókban a calreticulin gén (CALR) exon 9, néhányukban pedig thrombopoetin receptor gén (MPL) mutációja mutatható ki, de 10–15%-ban ezek egyike sincs jelen, ezeket tripla-negatív eseteknek nevezzük. A betegség tünetei a gyengeség, fejfájás, thrombohaemorrhagiás események mellett az erythromelalgia lehetnek. A splenomegalia általában mérsékelt fokú. A betegség prognózisa általában igen jó, a fő szövődményt a vascularis események jelentik. Az ET kezelésében elsődleges a thrombocyta aggregáció gátlás, de a 60 évnél idősebb és/vagy korábban már thromboembolián átesett betegek esetén cytoreduktív kezelés is javasolt. Az irodalmi adatok szerint a thrombosis kockázat nem függ össze a thrombocytosis mértékével.

  • 1

    Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127: 2391–2405.

  • 2

    Barbui T, Thiele J, Gisslinger H, et al. The 2016 revision of WHO classification of myeloproliferative neoplasms: clinical and molecular advances. Blood Rev. 2016; 30: 453–459.

  • 3

    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.

  • 4

    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.

  • 5

    Moulard O, Mehta J, Fryzek J, et al. Epidemiology of myelofibrosis, essential thrombocythaemia, and polycythaemia vera in the European Union. Eur J Hematol. 2014; 924: 289–297.

  • 6

    Jako J, Szerafin L. A Philadelphia-negatív krónikus myeloproliferativ kórképek epidemiológiai jellemzői Szabolcs-Szatmár-Bereg megyében. 33 év adatainak elemzése. Orv Hetil. 2017; 158: 572–578.

  • 7

    Campbell PJ, Baxter EJ, Beer PA, et al. Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations, and role in leukemic transformation. Blood 2006; 108: 3548–3555.

  • 8

    Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia 2010; 24: 112–1138.

  • 9

    Georgii A, Buhr T, Buesche G, et al. Classification and staging of Ph-negative myeloproliferative disorders by histopathology from bone marrow biopsies. Leuk Lymphoma 1996; 22 Suppl 1: 15–29.

  • 10

    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.

  • 11

    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 2007; 109: 2310–2313.

  • 12

    Rajnics P, Kellner Á, Karádi É, et al. Increased Lipocalin 2 level may have important role in thrombotic events in patients with polycythemia vera and essential thrombocythemia Leuk Res. 2016; 48: 101–106.

  • 13

    Budde U, Schaefer G, Mueller N, et al. Acquired von Willebrand’s disease in the myeloproliferative syndrome. Blood 1984; 64: 981–985.

  • 14

    Rumi E, Cazzola M. How I treat essential thrombocythemia. Blood 2016; 128: 2403–2414.

  • 15

    Rumi E, Pietra D, Ferretti V, et al. JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood 2014; 123: 1544–1551.

  • 16

    Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol. 2017; 92: 94–108.

  • 17

    Dameshek W. Some speculation on the myeloproliferative syndromes. Blood 1951; 6: 372–375.

  • 18

    Murphy S, Peterson P, Iland H, et al. Experience of the Polycythemia Vera Study Group with essential thrombocythemia: a final report on diagnostic criteria, survival, and leukemic transition by treatment. Semin Hematol. 1997; 34: 29–39.

  • 19

    Thiele J, Kvasnicka HM, Orazi A, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, IARC, 2008; pp. 48–50.

  • 20

    Landolfi R, Gennaro L. Prevention of thrombosis in polycythaemia vera and essential thrombocythaemia. Hematologica 2008; 93: 331–335.

  • 21

    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.

  • 22

    Pósfai É, Marton I, Nemes A, et al. Thrombotic events and importance of IPSET thrombosis risk evaluation score in essential thrombocythaemia. Orv hetil. 2015; 156: 558–563.

  • 23

    Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013; 369: 2379–2390.

  • 24

    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.

  • 25

    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.

  • 26

    Tefferi A, Lasho TL, Guglielmelli P, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv. 2016; 1: 21–30.

  • 27

    Tefferi A, Elliott M. Thrombosis in myeloproliferative disorders: prevalence, prognostic factors, and the role of leukocytes and JAK2V617F. Semin Thromb Hemost. 2007; 33: 313–320.

  • 28

    Alvarez-Larran 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.

  • 29

    Pascale S, Petrucci G, Dragani A, et al. Aspirin-insensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target. Blood 2012; 119: 3595–3603.

  • 30

    Wright CA, Tefferi A. A single institutional experience with 43 pregnancies in essential thrombocythemia. Eur J Haematol. 2001; 66: 152–159.

  • 31

    Harrison CN. Guideline for investigation and management of adults and children presenting with a thrombocytosis. Br J Hematol. 2010; 149: 352–375.

  • 32

    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: 1132–1136.

  • 33

    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.

  • 34

    Gisslinger H, Gotic M, Holowiecki J, et al. Anagrelide compared to hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood 2013; 121: 1720–1728.

  • 35

    Dombi P. Illés Á, Demeter J, et al. Anagrelide reduces thrombotic risk in essential thrombocythaemia vs. hydroxyurea plus aspirin. Eur J Haematol. 2017; 98: 106–111.

  • 36

    Kiladjian JJ, Giraudier S, Cassinat B. Interferon-alpha for the therapy of myeloproliferative neoplasms: targeting the malignant clone. Leukemia 2016; 30: 776–781.

  • 37

    Kiladjian JJ, Cassinat B, Chevret S, et al. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 2008; 112: 3065–3072.

  • 38

    Kiladjian JJ, Chevret S, Dosquet C, et al. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. J Clin Oncol. 2011; 29: 3907–3913.

  • 39

    Barosi G, Mesa R, Finazzi G, et al. Revised response criteria for polycythemia vera and essential thrombocythemia: a ELN and IWG-MRT consensus project. Blood 2013; 121: 4778–4781.

  • 40

    Barbui T, Barosi G, Birgegard G. Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European Leukemia Net. J Clin Oncol. 2011; 29: 761–770.