Desfecho e preditores de resposta aos inibidores de Tirosinoquinase de 2a geração em pacientes com Leucemia Mielóide Crônica em fase crônica resistentes ao Imatinibe
Outcome and predictors of response to second generation tyrosine kinase inhibitors in patients with Chronic Myeloid Leukemia in chronic phase resistant to Imatinibe
Fernanda da Cunha Vieira, Debora Bonito, Davimar M. Borducchi, Auro del Giglio, Patrícia Weinschenker Bollmann
Resumo
Objetivo: Avaliar o desfecho de pacientes com Leucemia Mielóide Crônica (LMC) em fase crônica (FC) em uso de inibidor de tirosino-quinase (ITKs) de segunda geração após falha com imatinibe e validar o escore de Hammersmith como preditor de resposta da terapia de segunda linha neste grupo de pacientes. Métodos: Entre maio de 2009 e dezembro de 2013, 63 pacientes tratados no serviço de Hematologia do Hospital Mário Covas com LMC em uso de imatinibe foram acompanhados. Destes, 25 pacientes falharam ao imatinibe e receberam tratamento com inibidores de segunda linha. Avaliações periódicas foram realizadas para definição de resposta, incluindo exame clínico, hemograma, cariótipo de medula óssea e pesquisa da proteína BCR-ABL por técnica de reverse transcriptase PCR. Os critérios de resposta do Leukemia Net foram adotados. O escore prognóstico de Hammersmith foi aplicado nos pacientes que iniciaram terapia de segunda linha. Resultados: Com mediana de follow-up de 20,2 meses, 9 pacientes apresentaram resposta citogenética completa, sendo 8 com Resposta Molecular Maior. Onze pacientes apresentaram progressão. O tempo mediano de Sobrevida Livre de Progressão foi 9,5 meses (IC95% 0-23,9). Quando o escore de Hammersmith foi aplicado na nossa população de 20 pacientes, 2 deles eram de baixo risco, 10 de risco intermediário e 8 de alto risco. Conclusão: Metade dos pacientes puderam ser resgatados com ITK de segunda geração apósfalha com imatinibe. Quanto ao escore de Hammersmith, este não conseguiu prever a resposta à terapia na nossa coorte de pacientes, provavelmente pela amostra por ser pequena.
Palavras-chave
Abstract
Objective: To evaluate the outcome of patients with Chronic Myeloid Leukaemia (CML) in chronic phase in use of a second generation tyrosine kinase inhibitor (TKIs) following imatinib failure and to validate the Hammersmith score as a predictor of therapy response of this second group of patients. Methods: Between May 2009 and December 2013, 63 patients treated at the hematology department of the Mário Covas Hospital with CML using imatinib were followed. Of these, 25 patients failed to imatinib and received treatment with second-line inhibitors. Periodic evaluations were performed to define response, including clinical examination, blood count, bone marrow karyotype and BCR-ABL protein by reverse transcriptase PCR. The Leukemia Net response criteria were adopted. The Hammersmith prognostic score was applied to patients who started second-line therapy. Results: With a median follow-up of 20.2 months, 9 patients presented complete cytogenetic response, 8 of which with Major Molecular Response. Eleven patients presented progression of disease. The median time to Progression Free Survival was 9.5 months (95% CI 0-23.9). When the Hammersmith score was applied in our population of 20 patients, 2 of them were classified as low risk, 10 as intermediate risk and 8 as high risk. Conclusion: Half of patients could be rescued with second generation TKI after imatinib failure. As for Hammersmith's score, it could not predict the response to therapy in our cohort of patients, probably because the sample was small.
Keywords
Referências
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