Artículos de revistas
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
Registro en:
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. Hospital Clinicas, Univ Sao Paulo, v. 70, p. 550-555 2015.
1807-5932
WOS:000359310800004
10.6061/clinics/2015(08)04
Autor
Ribeiro
Beatriz Felicio; Miranda
Eliana C. M.; de Albuquerque
Dulcineia Martins; Delamain
Marcia T.; Oliveira-Duarte
Gislaine; Almeida
Maria Helena; Vergilio
Bruna; Da Silveira
Rosana Antunes; Oliveira-Duarte
Vagner; Lorand-Metze
Irene; De Souza
Carmino A.; Pagnano
Katia B. B.
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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 for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary. 70 8
550 555 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Universidade de Campinas (UNICAMP), Centro de Hematologia e Hemotherapia, Campinas/SP, Brazil Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)