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Clin Lymphoma Myeloma Leuk ; 14(4): 305-18, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24468131

RESUMO

BACKGROUND: We have evaluated the ex vivo pharmacology of single drugs and drug combinations in malignant cells of bone marrow samples from 125 patients with acute myeloid leukemia using a novel automated flow cytometry-based platform (ExviTech). We have improved previous ex vivo drug testing with 4 innovations: identifying individual leukemic cells, using intact whole blood during the incubation, using an automated platform that escalates reliably data, and performing analyses pharmacodynamic population models. PATIENTS AND METHODS: Samples were sent from 24 hospitals to a central laboratory and incubated for 48 hours in whole blood, after which drug activity was measured in terms of depletion of leukemic cells. RESULTS: The sensitivity of single drugs is assessed for standard efficacy (EMAX) and potency (EC50) variables, ranked as percentiles within the population. The sensitivity of drug-combination treatments is assessed for the synergism achieved in each patient sample. We found a large variability among patient samples in the dose-response curves to a single drug or combination treatment. CONCLUSION: We hypothesize that the use of the individual patient ex vivo pharmacological profiles may help to guide a personalized treatment selection.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Feminino , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Medicina de Precisão , Resultado do Tratamento
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