Tyrosine kinase inhibitor treatment outcome in a single center cohort of chronic myeloid leukemia patients. The role of the T315I ABL kinase domain mutation

Introduction. Since the introduction of the tyrosine kinase inhibitor (TKI) imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), a dramatic improvement in hematologic, cytogenetic and molecular responses was noted. Also, the overall survival increased significantly. Unfortunately, in certain patients, resistance to TKI develops relatively early, especially due to point mutations in the ABL kinase domain, among which the T315I mutation confers resistance to all three currently available TKIs (imatinib, dasatinib, nilotinib). Methods. We performed a prospective study on 74 patients diagnosed with chronic phase CML, for whom we analyzed the T315I mutation. Mutational analysis was performed using ARMS-PCR (with subsequent confirmation by direct sequencing) at regular intervals of 6 months or in case of suboptimal response, loss of response or progression. Correlations between the T315I mutation and disease characteristics, response to treatment and survival were analyzed. A comparative analysis between patients positive and negative for the mutation was performed. The patients were followed and evaluated according to European Leukemia Net (ELN) criteria. Results. T315I mutation was detected in 3 patients (4.05%) and its presence was correlated with younger age at diagnosis, second line TKI therapy, progressive disease and decreased survival from the moment of detection. Conclusions. ARMS-PCR is a sensitive, easy to use method for the detection of T315I mutation in chronic phase CML patients