Haema 2012; 3(1): 37-44
by Nora-Athina Viniou, Panagiotis Diamantopoulos, Vassiliki Papadopoulou
1st Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, “Laiko” General Hospital, Athens
Abstract
Patients with chronic myelogenous leukemia do not invariably respond to treatment with imatinib. To date, there is no safe way to predict which patient will show primary or secondary resistance to the drug. Clinical, hematologic, cytogenetic and molecular criteria are used to assess treatment response. Treatment response assessment should be made in predetermined intervals according to the European Leukemia Net (ELN) and the National Comprehensive Cancer Network (NCCN) recommendations. In the era of second generation tyrosine kinase inhibitors (TKIs), patients not achieving a robust response to treatment with imatinib, as well as those with treatment intolerance are candidates for treatment switch to dasatinib or nilotinib. Treatment failure is largely caused by the emergence of mutations of the BCR/ABL kinase that are resistant to the drug. Among them, T315I is a mutation resistant to all currently available TKIs. For all the rest, the choice of the more suitable 2nd generation TKI should be made based on mutation analysis, the adverse event profile of the drugs as well as their kinetics, which determine the dietary restrictions accompanying their use. Other factors, such as the emergence of additional karyotypic aberrations and the low intracellular concentration of the human organic cation trans- porter – 1 (hOCT-1) may be responsible for imatinib treatment failure, although hOCT-1 intracellular concentration does not affect the effectiveness of 2nd generation TKIs. Comparative studies keep on providing data about the rational use of all three drugs, both as first and second line treatment.