Onkológia 4/2012

Management of pacients with CML resistant or intolerant to tyrosine kinase inhibitor – imatinib

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disorder, resulting from transformed progenitor haematopoietic stem cells. CML was the first human disease in which a specific abnormality of the karyotype „the Philadelphia (Ph) chromosome“ could be linked with leukaemogenesis. There is a new chimeric gene, BCR-ABL, which translates into a protein with increased tyrosine kinase activity. Nearly 40 years after the recognition of the chromosomal abnormality, a specific therapy was developed. CML is treated with tyrosine kinase inhibitors (TKI), the first of which was imatinib approved by the United States FDA (Food and Drug Administration) in 2001. The excellent results obtained with imatinib when used as initial therapy, and the availability of effective salvage therapy, redefined the CML treatment algorithm. Nearly all patients are offered therapy with imatinib at diagnosis, and for those who experience failure to therapy, a second-generation TKI is indicated. With this approach, the median survival for CML patients will probably exceed 20 years. Still, as we better understand the disease and improve the outcome of patients, we have uncovered new challenges and important questions that demand attention. In this article, we analyse the current status of therapy of CML, and we discuss some of the most relevant clinical questions that we face today.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, resistance to treatment, suboptimal response to treatment, treatment failure.