Title |
Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors – a single center experience
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Published in |
Clinics, August 2015
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DOI | 10.6061/clinics/2015(08)04 |
Pubmed ID | |
Authors |
Beatriz Felicio Ribeiro, Eliana C M Miranda, Dulcinéia Martins de Albuquerque, Márcia T Delamain, Gislaine Oliveira-Duarte, Maria Helena Almeida, Bruna Vergílio, Rosana Antunes da Silveira, Vagner Oliveira-Duarte, Irene Lorand-Metze, Carmino A De Souza, Katia B B Pagnano |
Abstract |
To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months. Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary. |
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Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 2% |
Unknown | 45 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Other | 7 | 15% |
Researcher | 5 | 11% |
Student > Master | 5 | 11% |
Professor | 3 | 7% |
Student > Bachelor | 2 | 4% |
Other | 9 | 20% |
Unknown | 15 | 33% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 12 | 26% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 13% |
Biochemistry, Genetics and Molecular Biology | 3 | 7% |
Agricultural and Biological Sciences | 3 | 7% |
Unspecified | 1 | 2% |
Other | 3 | 7% |
Unknown | 18 | 39% |