Der Internist

, Volume 44, Issue 8, pp 1011–1030

Chronische myeloproliferative Erkrankungen

Diagnostik und Therapie
  • E. Lengfelder
  • U. Berger
  • A. Reiter
  • A. Hochhaus
  • R. Hehlmann
Weiterbildung · Zertifizierte Fortbildung

Zusammenfassung

Die chronischen myeloproliferativen Erkrankungen (CMPE) sind neoplastische Erkrankungen der hämatopoetischen Stammzelle. Sie umfassen die chronische myeloische Leukämie (CML), die Polycythaemia vera, die essentielle Thrombozythämie, die primäre Osteomyelofibrose und Übergangsformen innerhalb dieser Erkrankungen sowie zwischen den CMPE und den Myelodysplasien. Hauptziele der Initialdiagnostik sind die genaue Klassifizierung der Erkrankung, die Erfassung von Risiko- und Prognosefaktoren sowie die Charakterisierung des malignen Klons mittels Zytogenetik und molekulargenetischer Methoden. Herkömmliche Therapeutika für alle CMPE sind Hydroxyurea und Interferon-α. Bei der CML führt die gezielte Hemmung der BCR-ABL-Tyrosinkinase mit Imatinib klinisch zu hohen Ansprechraten. Die bisher einzige kurative Therapie für alle Entitäten ist die allogene Stammzelltransplantation. Bei der CML sollte die Indikation auf der Basis der neueren Risikoscores gestellt werden. Bei den BCR-ABL-negativen CMPE ist sie nur bei ungünstigem Krankheitsverlauf in Erwägung zu ziehen.

Schlüsselwörter

Chronische myeloproliferative Erkrankungen Stammzelltransplantation Interferon α Hydroxyurea Imatinib 

Abstract

Chronic myeloproliferative disorders (CMPD) are neoplastic disorders of the hematopoietic stem cell. Four different entities are defined: chronic myeloid leukemia (CML), polycythemia vera, essential thrombocythaemia, and idiopathic myelofibrosis. In addition, overlapping entities within the CMPDs and between CMPDs and myelodysplastic syndrome have been described. Diagnostic measures are performed to classify the subtype exactly and to assess risk factors and prognosis. Cytogenetic and molecular analyses are mandatory for the characterization of the malignant clone. Hydroxyurea and interferon-alpha have proven effective in all CMPE. In CML, specific inhibition of the elevated ABL tyrosine kinase activity with imatinib is associated with high response rates. Allogeneic stem cell transplantation is the only curative treatment option for all entities. In CML, the decision-making analysis should be based on established scores. In BCR-ABL negative CMPDs an allogeneic stem cell transplantation should only be performed in patients with unfavorable prognosis.

Keywords

Chronic myeloproliferative disorders Allogeneic stem cell transplantation Interferon-alpha Hydroxyurea Imatinib 

Literatur

  1. 1.
    Anagrelide Study Group (1992) Anagrelide, a therapy for thrombocythemic states. Experience in 577 patients. Am J Med 92: 69–76PubMedGoogle Scholar
  2. 2.
    Apperley J, Gardembas M, Melo JV et al. (2002) Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 347: 481–487CrossRefPubMedGoogle Scholar
  3. 3.
    Cortelazzo S, Finazzi G, Ruggeri et al. (1995) Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 332: 1132–1136PubMedGoogle Scholar
  4. 4.
    Chronic Myeloid Leukemia Trialists' Collaborative Group (1997) Interferon alfa versus chemotherapy for chronic myeloid leukemia: a meta-analysis of seven randomized trials. J Natl Cancer Inst 89: 1616–1620PubMedGoogle Scholar
  5. 5.
    Cross NC, Reiter A (2002) Tyrosine kinase fusion genes in chronic myeloproliferative diseases. Leukemia 16: 1207–1212CrossRefPubMedGoogle Scholar
  6. 6.
    Gratwohl A, Hermans J, Goldman JM et al. (1998) Risk assessment for patients with chronic myeloid leukemia before allogeneic blood or marrow transplantation. Lancet 352: 1087–1092CrossRefPubMedGoogle Scholar
  7. 7.
    Gruppo Italiano Studio Polycythemia (1995) Polycythemia vera: the natural history of 1213 patients followed for 20 years. Ann Intern Med 123: 656–664PubMedGoogle Scholar
  8. 8.
    Hasford J, Pfirrmann M, Hehlmann R et al. (1998) A new prognostic score for the survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst 90: 850–858PubMedGoogle Scholar
  9. 9.
    Hochhaus A, Kreil S, Corbin A et al. (2001) Roots of clinical resistance to STI-571 cancer therapy. Science 293: 2163Google Scholar
  10. 10.
    Hochhaus A, Kreil S, Corbin AS et al. (2002) Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 16: 2190–2196CrossRefPubMedGoogle Scholar
  11. 11.
    Lengfelder E, Hochhaus A, Kronawitter et al. (1998) Should a platelet limit of 600×109/l be used as a diagnostic criterion in essential thrombocythemia? An analysis of the natural course including early stages. Brit J Haematol 100: 15–23CrossRefGoogle Scholar
  12. 12.
    Lengfelder E, Hehlmann R (2000) Polyzythämia vera: Aktueller Stand der Therapie. Dtsch Med Wschr 125: 1243–1247CrossRefPubMedGoogle Scholar
  13. 13.
    O'Brien S, Guilhot F, Larson RA et al. (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348: 994–1004CrossRefPubMedGoogle Scholar
  14. 14.
    Reiter A, Hehlmann R, Goldman JM, Cross NC (1999) Die 8p11-myeloproliferative Erkrankung. Med Klin 94: 207–210PubMedGoogle Scholar
  15. 15.
    Sawyers CL, Hochhaus A, Feldman E et al. (2002) Gleevec/GlivecTM (imatinib mesylate) induces hematologic and cytogenetic responses in patients with chronic myeloid leukemia in myeloid blast crisis: results of a phase II study. Blood 99: 3530–3539CrossRefPubMedGoogle Scholar
  16. 16.
    Silver RT, Woolf SH, Hehlmann R et al. (1999) Review: An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: developed for the American Society of Hematology. Blood 94: 1517–1536PubMedGoogle Scholar
  17. 17.
    Tefferi A (2000) Myelofibrosis with myeloid metaplasia. N Engl J Med 342: 1255–1265PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • E. Lengfelder
    • 1
    • 2
  • U. Berger
    • 1
  • A. Reiter
    • 1
  • A. Hochhaus
    • 1
  • R. Hehlmann
    • 1
  1. 1.II. Medizinische Klinik MannheimUniversität Heidelberg
  2. 2.III. Medizinische Klinik MannheimMannheim

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