Resistance to imatinib and the possibilities of use of the dose escalation of the drug in patients with chronic myeloid leukemia


Authors: J. Mayer 1;  H. Klamová 1;  D. Žáčková 1;  M. Doubek 1;  P. Cetkovský 1;  M. Krejčí 1;  D. Dvořáková 1
Authors‘ workplace: za organizaci Česká leukemická skupina - pro život, The CzEch Leukemia Study Group – for Life, CELL ;  Interní hematoonkologická klinika FN Brno, 2Ústav hematologie a krevní transfuze, Praha 1
Published in: Transfuze Hematol. dnes,13, 2007, No. 3, p. 133-141.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

The introduction of imatinib into the treatment of chronic myeloid leukemia represents a revolutionary therapeutic approach. Together with its excellent results, the issue of imatinib resistance – the significant cause of therapeutic failure – has emerged. The authors pay attention to the relation of the mechanism of action, pharmacokinetics and pharmacodynamics to the imatinib treatment results in the scale ranging from the BCR-ABL transcript reduction to the overall survival. In addition, the most frequent mechanisms of imatinib resistance, particularly the data about the BCR-ABL kinase domain mutations are summarized and the possibilities of the management of this problem are discussed. Besides the dose escalation of imatinib the new promising agents, particularly dasatinib and nilotinib are presented and discussed.

Key words:
chronic myeloid leukemia, imatinib, resistance to imatinib, BCR-ABL, BCR-ABL kinase domain mutations, dasatinib, nilotinib


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Haematology Internal medicine Clinical oncology

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