Dtsch Med Wochenschr 2015; 140(20): 1501-1506
DOI: 10.1055/s-0041-103336
Klinischer Fortschritt
Hämatologie und Onkologie
© Georg Thieme Verlag KG Stuttgart · New York

Diagnostik und Therapie der Polycythaemia vera im Jahre 2015

Diagnosis and treatment of polycythemia vera in the year 2015
Eva Lengfelder
1   III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim
,
Martin Griesshammer
2   Klinik für Hämatologie, Onkologie, Hämostaseologie und Palliativmedizin, Johannes Wesling Klinikum Minden
,
Steffen Koschmieder
3   Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation, Medizinische Fakultät, RWTH Uniklinik Aachen
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
07. Oktober 2015 (online)

   Lizenzen und Reprints

Erratum zu diesem Artikel:

Diagnostik und Therapie der Polycythaemia vera im Jahre 2015Dtsch Med Wochenschr 2015; 140(20): e256
DOI: 10.1055/s-0041-110562

Was ist neu?

  • Neue Entwicklungen bei Diagnosesicherung und Pathogenese: Hauptkriterien der zur Zeit noch aktuellen WHO-Klassifikation der Polycythaemia vera (PV) sind eine gesteigerte Erythrozytenmasse und der Nachweis eines klonalen Markers (JAK2-Mutation).

  • Klinische Symptome: Der Schweregrad der PV-Symptome ist häufig moderat, jedoch leiden viele Patienten an mehreren Symptomen, wodurch die Lebensqualität eingeschränkt ist.

  • Therapieziele und Risikostratifizierung: Bei in der Regel guter Überlebensprognose ist die Reduktion der potenziell bedrohlichen thromboembolischen Komplikationen primäres Therapieziel. Das Überleben wird signifikant von der Anzahl der vorliegenden Risikofaktoren beeinflusst.

  • Therapie: Aderlass, ASS und zytoreduktive Therapie (Hydroxyurea bzw. Interferon-alpha) sind die Eckpfeiler der Therapie. Der Tyrosinkinase-Inhibitor Ruxolitinib erweitert die Therapiemöglichkeiten bei einer Resistenz und Intoleranz gegenüber Hydroxyurea.

 

  • Literatur

  • 1 Dameshek W. Some speculations on myeloproliferative syndromes. Blood 1951; 6: 372-375
    Suche in Google Scholar
  • 2 Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973; 243: 290-293
    CrossrefSuche in Google Scholar
  • 3 Shtivelman E, Lifshitz B, Gale RP et al. Fused transcript of abl and bcr genes in chronic myelogenous leukemia. Nature 1985; 315: 550-554
    CrossrefSuche in Google Scholar
  • 4 James C, Ugo V, Couédic J et al. A unique clonal JAK2 mutation leading to constitutive signaling causes polycythaemia vera. Nature 2005; 434: 1144-1148
    CrossrefSuche in Google Scholar
  • 5 Moulard O, Mehta J, Fryzek J et al. Epidemiology of myelofibrosis, essential thrombocythemia, and polycythemia vera in the European Union. Eur J Haematol 2014; 92: 289-297
    CrossrefSuche in Google Scholar
  • 6 Tefferi A, Rumi E, Finazzi G et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia 2013; 27: 1874-1881
    CrossrefPubMedSuche in Google Scholar
  • 7 Gruppo Italiano Studio Polycythemia vera. The natural history of 1213 patients followed for 20 years. Ann Intern Med 1995; 123: 656-664
    CrossrefSuche in Google Scholar
  • 8 Chiewitz E, Thiede T. Complications and causes of death in polycythemia vera. Acta Med Scand 1962; 172: 513-523
    Suche in Google Scholar
  • 9 Cervantes F, Tassies D, Salgado C et al. Acute transformation in nonleukemic chronic myeloproliferative disorders: actuarial probability and main characteristics in a series of 218 patients. Acta Haematol 1991; 85: 124-127
    CrossrefSuche in Google Scholar
  • 10 Alvarez-Larrán A, Bellosillo B, Martínez-Avilés L et al. Postpolycythaemic myelofibrosis: frequency and risk factors for this complication in 116 patients. Br J Haematol 2009; 146: 504-509
    CrossrefSuche in Google Scholar
  • 11 Passasamonti F, Rumi E, Pietra D et al. A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia 2010; 24: 1574-1579
    CrossrefSuche in Google Scholar
  • 12 Finazzi G, Caruso V, Marchioli R et al. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood 2005; 105: 2664-2670
    CrossrefSuche in Google Scholar
  • 13 WHO classification of tumours of haemopoietic and lymphoid tissues. WHO Press; 2008: 40-43
    Suche in Google Scholar
  • 14 Tefferi A, Thiele J, Vannucchi AM, Barbui T. An overview on CALR and CSF3R mutations and a proposal for revision of WHO diagnostic criteria for myeloproliferative neoplasms. Leukemia 2014; 28: 1407-1413
    CrossrefSuche in Google Scholar
  • 15 Klampfl T, Gisslinger H, Harutyunyan AS et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013; 369: 2379-2390
    CrossrefSuche in Google Scholar
  • 16 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
    CrossrefSuche in Google Scholar
  • 17 Lengfelder E, Petrides PE, Grießhammer M. Polycythaemia vera. Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen 2014. www.dgho-onkopedia.de
    Suche in Google Scholar
  • 18 Siegel FP, Petrides PE. Angeborene und erworbene Polyzythämien. Dtsch Ärztebl 2008; 105: 62-68
    Suche in Google Scholar
  • 19 Vainchencker W, Dusa A, Constantinescu SN. JAKs in pathology: role of Janus kinases in hematopoietic malignancies and immunodeficiencies. Semin Cell Dev Biol 2008; 19: 385-393
    CrossrefSuche in Google Scholar
  • 20 O‘Shea JJ, Schwartz DM, Villarino AV et al. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med 2015; 66: 311-328
    CrossrefSuche in Google Scholar
  • 21 Lindsley RC, Ebert BL. The biology and clinical impact of genetic lesions in myeloid malignancies. Blood 2013; 122: 3741-3748
    CrossrefSuche in Google Scholar
  • 22 Lundberg P, Karow A, Nienhold R et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood 2014; 123: 2220-2228
    CrossrefSuche in Google Scholar
  • 23 Ortmann CA, Kent DG, Nangalia J et al. Effect of mutation order on myeloproliferative neoplasms. N Engl J Med 2015; 372: 601-612
    CrossrefSuche in Google Scholar
  • 24 Falanga a, Marcheti M. Thrombosis in myeloproliferative neoplasms. Semin Thromb Hemost 2014; 40: 348-358
    Thieme ConnectSuche in Google Scholar
  • 25 Dentali F, Squizzato A, Brivio L. JAK2V617F mutation for the early diagnosis of Ph- myeloproliferative neoplasms in patients with venous thromboembolism: a meta-analysis. Blood 2009; 113: 5617-5623
    CrossrefPubMedSuche in Google Scholar
  • 26 Smalberg JH, Arends LR, Valla DC et al. Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis: a meta-analysis. Blood 2012; 120: 4921-4928
    CrossrefSuche in Google Scholar
  • 27 Dentali F, Ageno W, Rumi E et al. Cerebral venous thrombosis and myeloproliferative neoplasms: results from two large databases. Thromb Res 2014; 134: 41-43
    CrossrefSuche in Google Scholar
  • 28 Kiladjian JJ, Cervantes F, Leebeek FW et 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
    CrossrefSuche in Google Scholar
  • 29 Scherber R, Dueck AC, Johansson P et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood 2011; 1 18: 401-408
    Suche in Google Scholar
  • 30 Mesa R, Miller CB, Thyne M et al. Impact of Myeloproliferative Neoplasms (MPNs) on Patients’ Overall Health and Productivity: Results from the MPN Landmark Survey in the United States. Blood 2014; 124 Abstract 3183
    Suche in Google Scholar
  • 31 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
    CrossrefSuche in Google Scholar
  • 32 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
    CrossrefPubMedSuche in Google Scholar
  • 33 Barbui T, Finazzi G, Falanga A. Myeloproliferative neoplasms and thrombosis. Blood 2013; 122: 2176-2184
    CrossrefSuche in Google Scholar
  • 34 Bonicelli G, Abdulkarim K, Mounier M et al. Leucocytosis and thrombosis at diagnosis are associated with poor survival in polycythaemia vera: a population-based study of 327 patients. Br J Haematol 2013; 160: 251-254
    CrossrefSuche in Google Scholar
  • 35 Geyer HL, Mesa R. Therapy for myeloproliferative neoplasms: when, which agent, and how?. Blood 2014; 24: 3529-3537
    Suche in Google Scholar
  • 36 Marchioli R, Finazzi G, Specchia G et al. CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 2013; 368: 22-33
    CrossrefSuche in Google Scholar
  • 37 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
    CrossrefSuche in Google Scholar
  • 38 Najean Y, Dresch C, Rain JD. The very-long-term course of polycythemia: a complement to the previously published data of the polycythemia vera study group. Br J Haematol 1993; 86: 233-235
    Suche in Google Scholar
  • 39 Berk PD, Goldberg JD, Silverstein MN et al. Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med 1981; 304: 441-447
    CrossrefSuche in Google Scholar
  • 40 Björkholm M, Derolf AR, Hultcrantz M et al. Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms. J Clin Oncol 2011; 29: 2410-2415
    CrossrefSuche in Google Scholar
  • 41 Barosi G, Birgegard G, Finazzi G et al. A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process. Br J Haematol 2010; 148: 961-963
    CrossrefSuche in Google Scholar
  • 42 Alvarez-Larrán A, Pereira A, Cervantes F et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood 2012; 119: 1363-1369
    CrossrefSuche in Google Scholar
  • 43 Lengfelder E, Berger U, Hehlmann R. Interferon alpha in the treatment of polycythemia vera. Ann Hematol 2000; 79: 103-109
    CrossrefPubMedSuche in Google Scholar
  • 44 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
    CrossrefSuche in Google Scholar
  • 45 Quintás-Cardama A, Kantarjian H, Manshouri T et al. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 2009; 27: 5418-5124
    CrossrefSuche in Google Scholar
  • 46 Haanen C, Mathe G, Hayat M. Treatment of polycythemia vera by radiophosphorus or busulfan: a randomized trial. Br J Cancer 1981; 44: 75-80
    CrossrefSuche in Google Scholar
  • 47 Kuriakose ET, Gjoni S, Wang YL et al. JAK2V617F allele burden is reduced by busulfan therapy: a new observation using an old drug. Haematologica 2013; 98: e135-137
    CrossrefSuche in Google Scholar
  • 48 Tefferi A. JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths. Blood 2012; 119: 2721-2730
    CrossrefSuche in Google Scholar
  • 49 Harrison C, Kiladjian JJ, Al-Ali HK et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012; 366: 787-798
    CrossrefSuche in Google Scholar
  • 50 Verstovsek S, Mesa RA, Gotlib J et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012; 366: 799-807
    CrossrefSuche in Google Scholar
  • 51 Vannucchi AM, Kiladjian JJ, Griesshammer M et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med 2015; 372: 426-435
    CrossrefPubMedSuche in Google Scholar
  • 52 Finazzi G, Vannucchi AM, Martinelli V et al. A phase II study of Givinostat in combination with hydroxycarbamide in patients with polycythaemia vera unresponsive to hydroxycarbamide monotherapy. Br J Haematol 2013; 161: 688-694
    CrossrefSuche in Google Scholar
  • 53 Bjørn ME, de Stricker K, Kjær L et al. Combination therapy with interferon and JAK1–2 inhibitor is feasible: Proof of concept with rapid reduction in JAK2V617F-allele burden in polycythemia vera. Leuk Res Rep 2014; 3: 73-75
    Suche in Google Scholar