[Therapy of chronic myelogenous leukemia in 2004]

Chronic myelogenous leukemia constitutes a clinical model for other neoplastic diseases. The cytogenetic hallmark of CML, the Ph chromosome with the molecular juxtaposition of BCR and ABL genes and the multistep pathogenesis with the stable chronic phase, the accelerated phase and the terminal blast crisis provide the background for the translation of molecular-cytogenetic findings into clinical practice. The systematic development of the selective BCR-ABL inhibitor imatinib was based on the discovery of the molecular pathogenesis of CML. Promising preclinical data were confirmed in phase I-III trials. Concerning hematologic and cytogenetic response and adverse effects imatinib is superior to interferon alpha. Open questions are treatment duration in patients with good response, long term side effects, persistence of minimal residual disease in almost all patients, development of resistance after long term therapy, and the efficacy of combination treatments. Prospective clinical trials, e. g. CML study IV of the German CML Study Group, should answer these questions. The impact of the various treatment modalities (imatinib, interferon alpha, ara-C, allogeneic stem cell transplantation) will be elucidated. The recruitment of newly diagnosed CML patients into CML-study IV is recommended.