Dasatinib in second line treatment of chronic myeloid leukaemia in patients with imatinib resistance or intolerance treated at the Clinic of Haematology and Transfusiology
Bratislava between 2007 and 2011


Authors: M. Martišová ;  Z. Sninská ;  A. Hatalová ;  E. Demečková ;  M. Mistrík
Authors‘ workplace: Klinika hematológie a transfuziológie LFUK, SZU a UNB, Bratislava
Published in: Transfuze Hematol. dnes,18, 2012, No. 3, p. 105-111.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

Introduction:
Chronic myelogenous leukaemia is the first oncologic disease associated with a concrete chromosomal aberration termed the Philadelphia chromosome, which gives rise to the BCR-ABL1 fusion gene. The pathological protein arising from the transcription and translation of this gene has tyrosine kinase activity and is able to induce malignant transformation of the given cell. Bcr-Abl tyrosine kinase represents a pathogenetically relevant molecular target and disease remission can be achieved by its inhibition. Tyrosine kinase inhibitors have led to a revolution in the treatment of chronic myelogenous leukaemia and have improved patient prognosis. The initial success of imatinib – a representative of the first generation of tyrosine kinase inhibitors – however gave rise over time to several issues. Imatinib led to the selection of a group of patients who fail to respond optimally to treatment, lose the initially achieved treatment response or who do not tolerate imatinib. Aiming to offer a more optimal treatment alternative for these patients, researchers have tried to find a superior and more effective Bcr-Abl inhibitor. Thus, 2nd generation tyrosine kinase inhibitors were discovered, including dasatinib. Dasatinib improved patient overall survival as well as prognosis.

Study group and methodology:
The group included 14 patients with an initially demonstrated diagnosis of chronic myeloid leukaemia in chronic phase. Patients were treated at the Clinic of Haematology and Transfusiology, Medical Faculty of Comenius University, Slovak Medical University and University Hospital Bratislava. All patients underwent first line treatment with imatinib and experienced treatment failure because of resistance, suboptimal response or imatinib intolerance. Patients were then treated by the 2nd generation of tyrosine kinase inhibitor – dasatinib from January 1, 2007 until July 31, 2012. Efficacy of dasatinib was evaluated according to the achievement of cytogenetic and molecular response at certain time points (3, 6, 9 and 12 months). Tolerability and overall survival were evaluated throughout the whole treatment period.

Aim:
To show the efficacy and tolerability of dasatinib in patients following imatinib failure.

Conclusion:
Dasatinib is able to achieve good cytogenetic and molecular responses with an acceptable safety profile. Its efficacy and tolerability are lower in the progressive phases of the disease.

Key words:
2nd generation Bcr-Abl tyrosine kinase inhibitors, dasatinib, second line treatment, efficacy, tolerability


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Labels
Haematology Internal medicine Clinical oncology
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