Therapie der chronischen myeloischen Leukämie - Ziel ist die hämatologische und zytogenetische Remission

Die gesamte Therapie und auch die Prognose der Patienten mit chronischer myeloischer Leukämie (CML) hat sich seit Einführung des Tyrosinkinaseinhibitors Imatinib entscheidend verbessert. So gibt es inzwischen für die Behandlung von Patienten in der chronischen Phase der Erkrankung wissenschaftlich gut fundierte Empfehlungen zum Einsatz dieses Medikaments. Bei Unverträglichkeit oder Unwirksamkeit von Imatinib können alternativ Dasatinib oder Nilotinib, zwei weitere Substanzen aus der Klasse der Tyrosinkinaseinhibitoren, eingesetzt werden. In fortgeschrittenen Krankheitsstadien ist die jeweilige Vortherapie für eine Therapieentscheidung zu berücksichtigen. Grundsätzlich gilt jedoch, dass CML-Patienten die Teilnahme an klinischen Studien empfohlen werden sollte.

Both the treatment strategy and the prognosis of patients with chronic myeloid leukaemia (CML) has significantly improved since the introduction of the tyrosine kinase inhibitor imatinib. For patients in chronic phase CML, there are good science-based recommendations for the treatment with imatinib. In the case of imatinib intolerance or resistance, the novel tyrosine kinase inhibitors dasatinib or nilotinib can be administered. The individual pre-treatment has to be respected for therapy decisions in advanced phases of CML. Patients should be advised to take part in clinical studies.

Key words

chronic myeloid leukaemia (CML) - chronic phase CML - advanced phase CML - treatment - imatinib intolerance - imatinib resistance

Literatur

• 1 Alvarez RH, Kantarjian H, Cortes JE.. The biology of chronic myelogenous leukemia: implications for imatinib therapy.  Semin Hematol. 2007;  44
• 2 Baccarani M, Saglio G, Goldman J. et al. . Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet.  Blood. 2006;  108 1809-1820
• 3 Cortes J, Rousselot P, Kim DW. et al. . Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis.  Blood. 2007;  109 3207-3213
• 4 Druker BJ.. Imatinib as paradigm of targeted therapies.  Adv Cancer Res. 2004;  91 1-30
• 5 Druker BJ, Guilhot F, O'Brien SG. et al. . Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia.  N Engl J Med. 2006;  355 2408-2417
• 6 Frame D.. Chronic myeloid leukemia: standard treatment options.  Am J Health Syst Pharm. 2006;  63 21-22
• 7 Fruehauf S, Topaly J, Buss EC. et al. . Imatinib combined with mitoxantrone/etoposide and cytarabine is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis.  Cancer. 2007;  109 1543-1549
• 8 Gambacorti-Passerini C, Brümmendorf T, Kantarjian H. et al. .Bosutinib (SKI-606) exhibits clinical activity in patients with Philadelphia chromosome positive CML or ALL who failed Imatinib. ASCO 2007
• 9 Garcia-Manero G, Talpaz M, Kantarjian HM.. Current therapy of chronic myelogenous leukemia.  Intern Med. 2002;  41 254-264
• 10 Giles FJ, Cortes J, Jones D. et al. . MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation.  Blood. 2007;  109 500-502
• 11 Goldman JM, Melo J.. Chronic myeloid leukaemia - advances in biology and new approaches to treatment.  N Engl J Med. 2003;  349 1451-1464
• 12 Guilhot F, Apperley J, Kim DW. et al. . Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase.  Blood. 2007;  109 4143-4150
• 13 Hehlmann R, Berger U, Pfirrmann M. et al. . Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia.  Blood. 2007;  109 4686-4692
• 14 Hehlmann R, Berger U, Pfirrmann M. et al. . Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon alpha and hydroxyurea.  Leukemia. 2003;  17 1529-1237
• 15 Hehlmann R, Heimpel H, Hasford al. J et. Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia.The German CML Study Group.  Blood. 1994;  84 4064-4077
• 16 Hehlmann R, Hochhaus A, Baccarani M. European Leukemia Net. . Chronic myeloid leukemia.  Lancet. 2007;  370 342-350
• 17 Hochhaus A.. Chronic myelogenous leukemia (CML): resistance to tyrosine kinase inhibitors.  Ann Oncol. 2006;  17
• 18 Hochhaus A, Berger U, Hehlmann R.. Chronische myeloische Leukämie - Empfehlungen zur Diagnostik und Therapie. Bremen, London, Boston: UNI-MED Verlag 2004
• 19 Jabbour E, Cortes J, Kantarjian H.. Dasatinib for the treatment of Philadelphia chromosome-positive leukaemias.  Expert Opin Investig Drugs. 2007;  16 679-687
• 20 Kantarjian H, Pasquini R, Hamerschlak N. et al. . Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial.  Blood. 2007;  109 5143-5150
• 21 Kantarjian H, Talpaz M, O'Brien S. et al. . Survival benefit with imatinib mesylate therapy in patients with accelerated-phase chronic myelogenous leukaemia - comparison with historic experience.  Cancer. 2005;  103 2099-2108
• 22 Kantarjian HM, Giles F, Gattermann N. et al. . Nilotinib (formerly AMN107), a highly selective Bcr-Abl tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance.  Blood. 2007;  22
• 23 Kantarjian HM, Talpaz M, Giles F. et al. . New insights into the pathophysiology of chronic myeloid leukaemia and imatinib resistance.  Ann Intern Med. 2006;  145 913-923
• 24 Kantarjian HM, Talpaz M, O'Brian S. et al. . Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukaemia.  Blood. 2003;  101 473-475
• 25 Hydroxyurea versus busulphan for chronic myeloid leukaemia: an individual patient data meta-analysis of three randomized trials.  Br J Haematol. 2000;  110 573-576
• 26 Quintas-Cardama A, Kantarjian H, Garcia-Manero G. et al. . A pilot study of imatinib, low-dose cytarabine and idarubicin for patients with chronic myeloid leukemia in myeloid blast phase.  Leuk Lymphoma. 2007;  48 283-289
• 27 Quintas-Cardama A, Kantarjian H, Garcia-Manero G. et al. . Phase I/II study of subcutaneous homoharringtonine in patients with chronic myeloid leukemia who have failed prior therapy.  Cancer. 2007;  109 248-255
• 28 Radujkovic A, Schad M, Topaly J. et al. . Synergistic activity of imatinib and 17-AAG in imatinib-resistant CML cells overexpressing BCR-ABL-Inhibition of P-glycoprotein function by 17-AAG.  Leukemia. 2005;  19 1198-1206
• 29 Radujkovic A, Topaly J, Fruehauf S, Zeller WJ.. Combination treatment of imatinib-sensitive and -resistant BCR-ABL-positive CML cells with imatinib and farnesyltransferase inhibitors.  Anticancer Res. 2006;  26 2169-2177
• 30 Shah NP, Kim DW, Kantarjian HM. et al. .Dasatinib 50 mg or 70 mg BID compared to 100 mg or 140 mg QD in patients with CML in chronic phase (CP) who are resistant to or intolerant to imatinib: One-year results of CA180034. ASCO 2007
• 31 Topaly J, Zeller WJ, Fruehauf S.. Combination therapy with imatinib mesylate (STI571): synopsis of in vitro studies.  Br J Haematol.. 2002;  119 3-14
• 32 Weisser M, Schleuning M, Haferlach C. et al. . Allogeneic stem-cell transplantation provides excellent results in advanced stage chronic myeloid leukemia with major cytogenetic response to pre-transplant imatinib therapy.  Leuk Lymphoma. 2007;  48 295-301

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