Imatinib mesylate, as target therapy, is highly efficient in chronic myelogenous leukemia. A challenge is primary and secondary resistance, particularly in the advanced phases of the disease. In secondary resistance, point mutations in the ABL dominion are the most common mechanism. From October 2000 to December 2005, 112 patients were investigated in the Hematology and Hemotherapy Service of Santa Casa of Sao Paulo. The aim was to characterize the profile of resistance and study the presence of the mutation. The majority of resistant patients were in the most advanced phases of the disease. Risk factors for resistance in the chronic phase were a platelet count higher than 450,000/mm3 before imatinib treatment or less than 50,000/mm3 during treatment. The total hematological response rate and the time to achieve this were similar between resistant and non-resistant patients. Lower overall survival was observed with resistance. It was notable that ten resistant patients had complete cytogenetic responses after 12 months (late responses) with both hematological and cytogenetic response rates similar to non-resistant patients (100%). Survival free from progression was similar up to 40 months and the overall survival rate was comparable up to 70 months. The overall survival and response to treatment were better than for the other resistant patients. In respect to the investigation of mutations, 22 resistant patients were investigated with eight presenting with the mutation (36.4%) The presence of blast cells in the peripheral blood at diagnosis of patients in the chronic phase was characterized as a higher risk factor for this mutation.
Chronic myelogenous leukemia; tyrosine-kinase inhibitor; imatinib mesylate; resistance; mutation
