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Pharmacological profiles of acute myeloid leukemia treatments in patient samples by automated flow cytometry: a bridge to individualized medicine

Autores: Bennett, T. A.; Montesinos, P.; Moscardo, F.; Martínez-Cuadrón, D.; Martínez, J.; Sierra, J.; García, R.; Pérez-de-Oteyza, J.; Fernández, P.; Serrano, J.; Fernández, A.; Herrera, P.; González, A.; Bethancourt, C .; Rodríguez-Macías, G.; Alonso, A.; Vera, J. A.; Navas, B.; Lavilla, E.; López, J. A.; Jiménez, S.; Simiele, A.; Vidriales, B.; González, B. J.; Hernández-Rivas, J. A.; Burgaleta, C.; Mascuñano, R. C.; Bautista, G.; Pérez-Simón, J. A.; Fuente-Ade, L.; Rayón, C.; Fernández de Trocóniz Fernández, José Ignacio; Janda, A.; Bosanquet, A. G.; Hernández-Campo, P.; Primo, D.; López, R.; Liebana, B.; Rojas, J. L.; Gorrochategui, J.; Sanz, M. A.; Ballesteros, J.
ISSN: 2152-2650
Volumen: 14
Número: 4
Páginas: 305 - 318
Fecha de publicación: 2014
We have estimated the pharmacological sensitivity and synergism of 125 individual patient samples for all drugs and combination treatments for acute myeloid leukemia in the context of the overall patient population. Each ex vivo pharmacological profile identifies drugs and treatments for which the patient's malignant cells are particularly sensitive or resistant, assisting in the selection of individualized treatments. 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 (E-MAX) 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.