Der Onkologe

, Volume 18, Issue 12, pp 1084–1092 | Cite as

Individualisierte Therapie der akuten myeloischen Leukämie

Leitthema

Zusammenfassung

Das Verständnis der Biologie der akuten myeloischen Leukämie und die Anzahl der bekannten zytogenetischen und molekularen Veränderungen nehmen rasant zu. Die Diagnostik wird komplexer, und neue therapeutische Möglichkeiten entstehen. Eine erhebliche Diversifizierung der Erkrankung ist die Folge. Neue Klassifikations- und Scoringsysteme versuchen diese Diversifizierung zu kategorisieren und Grundlagen für risikoadaptierte und subgruppenspezifische Therapiestrategien zu legen. Klinische Entscheidungspfade und insbesondere auch das Gespräch mit dem Patienten sind zu einer echten Herausforderung geworden. Der vorliegende Beitrag gibt deshalb einen Überblick zur modernen Diagnostik, neuen Prognosefaktoren und insbesondere innovativen Therapieansätzen. Diese werden im Kontext der etablierten Standardtherapie bewertet und die Perspektiven für die Zukunft aufgezeigt.

Schlüsselwörter

Akute myeloische Leukämie Erwachsene Prognostische Faktoren Scoringsysteme Individualisierte Therapie 

Individualized therapy of acute myeloid leukemia

Abstract

The understanding of the biology of acute myeloid leukemia and the number of known cytogenetic and molecular changes is increasing rapidly. The diagnosis is becoming more complex and new therapeutic options are arising. A significant diversification of the disease is the result. New classification and scoring systems attempt to categorize this diversity and to lay the foundations for risk-adapted and subgroup-specific treatment strategies. Clinical decision paths and in particular the interview with the patient have become a real challenge. This review therefore provides an overview of modern diagnostics, new prognostic factors and in particular innovative therapeutic approaches. These are evaluated in the context of the established standard of care and the prospects for the future are highlighted.

Keywords

Acute myeloid leukemia Adults Prognostic factors Scoring-systems Individualized therapy 

Literatur

  1. 1.
    Appelbaum FR, Gundacker HM, Head DR et al (2006) Age and acute myeloid leukemia. Blood 107:3481–3485CrossRefPubMedGoogle Scholar
  2. 2.
    Baer MR (2002) Detection of minimal residual disease in acute myeloid leukemia. Curr Oncol Rep 4:398–402CrossRefPubMedGoogle Scholar
  3. 3.
    Bene MC, Bernier M, Casasnovas RO et al (1998) The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL). Blood 92:596–599PubMedGoogle Scholar
  4. 4.
    Bennett JM, Catovsky D, Daniel MT et al (1976) Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 33:451–458CrossRefPubMedGoogle Scholar
  5. 5.
    Bernasconi P, Boni M, Cavigliano PM et al (2002) Molecular genetics of acute myeloid leukemia. Ann N Y Acad Sci 963:297–305CrossRefPubMedGoogle Scholar
  6. 6.
    Bradstock KF, Matthews JP, Lowenthal RM et al (2005) A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood 105:481–488CrossRefPubMedGoogle Scholar
  7. 7.
    Buccisano F, Maurillo L, Spagnoli A et al (2010) Cytogenetic and molecular diagnostic characterization combined to postconsolidation minimal residual disease assessment by flow cytometry improves risk stratification in adult acute myeloid leukemia. Blood 116:2295–2303CrossRefPubMedGoogle Scholar
  8. 8.
    Buchner T, Hiddemann W, Berdel WE et al (2003) 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group. J Clin Oncol 21:4496–4504CrossRefPubMedGoogle Scholar
  9. 9.
    Cheson BD, Bennett JM, Kopecky KJ et al (2003) Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 21:4642–4649CrossRefPubMedGoogle Scholar
  10. 10.
    Dohner H, Estey EH, Amadori S et al (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115:453–474CrossRefPubMedGoogle Scholar
  11. 11.
    Fernandez HF, Sun Z, Yao X et al (2009) Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 361:1249–1259CrossRefPubMedGoogle Scholar
  12. 12.
    Hellenbrecht A, Messerer N, Gokbuget N (2008) Häufigkeit von Leukämien bei Erwachsenen in Deutschland. http://www.kompetenznetz-leukaemie.de/content/aerzte/epidemiologie/leukaemiehaeufigkeit/Google Scholar
  13. 13.
    Kronke J, Schlenk RF, Jensen KO et al (2011) Monitoring of minimal residual disease in NPM1-mutated acute myeloid leukemia: a study from the German-Austrian acute myeloid leukemia study group. J Clin Oncol 29:2709–2716CrossRefPubMedGoogle Scholar
  14. 14.
    Krug U, Rollig C, Koschmieder A et al (2010) Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet 376:2000–2008CrossRefPubMedGoogle Scholar
  15. 15.
    Leone G, Mele L, Pulsoni A et al (1999) The incidence of secondary leukemias. Haematologica 84:937–945PubMedGoogle Scholar
  16. 16.
    Lo-Coco F, Avvisati G, Vignetti M et al (2010) Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood 116:3171–3179CrossRefPubMedGoogle Scholar
  17. 17.
    Mayer RJ, Davis RB, Schiffer CA et al (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med 331:896–903CrossRefPubMedGoogle Scholar
  18. 18.
    Patel JP, Gonen M, Figueroa ME et al (2012) Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 366:1079–1089CrossRefPubMedGoogle Scholar
  19. 19.
    Pfirrmann M, Ehninger G, Thiede C et al (2012) Prediction of post-remission survival in acute myeloid leukaemia: a post-hoc analysis of the AML96 trial. Lancet Oncol 13:207–214CrossRefPubMedGoogle Scholar
  20. 20.
    Recher C, Dos SC, Demur C et al (2005) mTOR, a new therapeutic target in acute myeloid leukemia. Cell Cycle 4:1540–1549CrossRefPubMedGoogle Scholar
  21. 21.
    Rollig C, Thiede C, Gramatzki M et al (2010) A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial. Blood 116:971–978CrossRefPubMedGoogle Scholar
  22. 22.
    Sanz MA, Martin G, Gonzalez M et al (2004) Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood 103:1237–1243CrossRefPubMedGoogle Scholar
  23. 23.
    Schaich M, Rollig C, Soucek S et al (2011) Cytarabine dose of 36 g/m(2) compared with 12 g/m(2) within first consolidation in acute myeloid leukemia: results of patients enrolled onto the prospective randomized AML96 study. J Clin Oncol 29:2696–2702CrossRefPubMedGoogle Scholar
  24. 24.
    Schaich M, Soucek S, Thiede C et al (2005) MDR1 and MRP1 gene expression are independent predictors for treatment outcome in adult acute myeloid leukaemia. Br J Haematol 128:324–332CrossRefPubMedGoogle Scholar
  25. 25.
    Schaich M, Ehninger G (2006) Diagnostik und Therapie der akuten myeloischen Leukämie des Erwachsenen. Onkologe 12:1003–1011CrossRefGoogle Scholar
  26. 26.
    Schlenk RF, Dohner K, Krauter J et al (2008) Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 358:1909–1918CrossRefPubMedGoogle Scholar
  27. 27.
    Schlenk RF, Dohner K, Mack S et al (2010) Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from matched related and matched unrelated donors in younger adults with high-risk acute myeloid leukemia: German-Austrian trial AMLHD98A. J Clin Oncol 28:4642–4648CrossRefPubMedGoogle Scholar
  28. 28.
    Schnittger S, Kohl TM, Haferlach T et al (2006) KIT-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood 107:1791–1799CrossRefPubMedGoogle Scholar
  29. 29.
    Swerdlow SH, Campo E, Harris NL et al (Hrsg) (2008) World Health Organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC LyonGoogle Scholar
  30. 30.
    Thiede C, Steudel C, Mohr B et al (2002) Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 99:4326–4335CrossRefPubMedGoogle Scholar
  31. 31.
    Vellenga E, Putten W van, Ossenkoppele GJ et al (2011) Autologous peripheral blood stem cell transplantation for acute myeloid leukemia. Blood 118:6037–6042CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Medizinische Klinik und Poliklinik IUniversitätsklinikum Carl Gustav CarusDresdenDeutschland

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