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
Clinics
; 70(8): 550-555, 08/2015. tab, graf
Article
em En
| LILACS
| ID: lil-753967
Biblioteca responsável:
BR1.1
ABSTRACT
OBJECTIVE:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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 ...Palavras-chave
Texto completo:
1
Base de dados:
LILACS
Assunto principal:
Pirimidinas
/
Proteínas Tirosina Quinases
/
Resistência a Medicamentos
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Leucemia Mielogênica Crônica BCR-ABL Positiva
/
Inibidores de Proteínas Quinases
/
Dasatinibe
/
Antineoplásicos
Tipo de estudo:
Evaluation_studies
/
Guideline
Limite:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clinics
Assunto da revista:
MEDICINA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Brasil