RESUMO
The correlation between imatinib (IM) trough plasma concentration (Cmin) and clinical response was assessed in patients with chronic-phase chronic myeloid leukemia. The Cmin correlated with neither the achievement of complete cytogenetic response (977 vs. 993 ng/ml, P = 0.48) nor a major molecular response (1,044 vs. 818 ng/ml, P = 0.17). Although this was significantly higher in patients with complete molecular response (CMR) than in those without (1,430 vs. 859 ng/ml, P = 0.04), the difference was not significant in the sub-population treated with a standard dose of IM (400 mg/day). Finally, multivariate analysis showed that the IM standard dose, but not Cmin, was predictive of the achievement of CMR. We thus suggest that, in practical clinics at least, adherence to the standard dose is the most important factor for the achievement of CMR.
Assuntos
Proteínas de Fusão bcr-abl/antagonistas & inibidores , Leucemia Mieloide de Fase Crônica/sangue , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Piperazinas/farmacocinética , Inibidores de Proteínas Quinases/farmacocinética , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/farmacocinética , Idoso , Benzamidas , Estudos Transversais , Análise Citogenética , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Feminino , Proteínas de Fusão bcr-abl/sangue , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib , Hibridização in Situ Fluorescente , Japão , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Tirosina Quinases/sangue , Proteínas Tirosina Quinases/genética , Pirimidinas/administração & dosagem , Indução de Remissão/métodos , Estudos Retrospectivos , Resultado do TratamentoAssuntos
Basófilos/citologia , Cromossomos Humanos Par 12 , Cromossomos Humanos Par 5 , Eosinofilia/diagnóstico , Síndromes Mielodisplásicas/diagnóstico , Translocação Genética , Adolescente , Adulto , Sequência de Aminoácidos , Sequência de Bases , Criança , Eosinofilia/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Síndromes Mielodisplásicas/complicações , Análise de Sequência de DNARESUMO
Results of recent studies with animal models suggest that expression of MLL fusion proteins promotes acute leukemogenesis. However, the most potent MLL fusion proteins are not sufficient for the development of acute myeloid leukemia (AML). The clinical data on the pathogenesis of this type of leukemia are limited. We analyzed the case of a patient with therapy-related AML with MLL rearrangement. The patient initially developed AML with t(8;21). Although the patient achieved complete remission with chemotherapy, an abnormal karyotype, inv(11)(q21q23), was detected. After 6-year persistence of a clone with the inversion 11 karyotype in the bone marrow, secondary AML developed. Results of fluorescence in situ hybridization analysis combined with magnet-activated cell sorting analysis showed that MLL rearrangement was detected in CD34+ and CD13+ fractions but not in a CD3+ fraction of the bone marrow. There were 2 important clinical findings. One was that MLL rearrangement was not sufficient for the development of leukemia. The other was that MLL rearrangement targets specific lineages.
