Pharmacological profiles of acute myeloid leukemia treatments in patient samples by automated flow cytometry

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...

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Detalles Bibliográficos
Autores: Bennett, Teresa A., Montesinos, Pau|||0000-0002-3275-5593, Moscardo, Federico, Martinez-Cuadron, David, Martinez, Joaquin, Sierra, Jorge|||0000-0002-7966-0356, García, Raimundo, Perez de Oteyza, Jaime|||0000-0002-8338-2037, Fernandez, Pascual, Serrano, Josefina, Fernandez, Angeles, Herrera, Pilar|||0000-0002-4118-7110, Gonzalez, Ataulfo, Bethancourt, Concepción, Rodriguez-Macias, Gabriela, Alonso, Arancha, Vera, Juan A., Navas Elorza, Begona, Lavilla, Esperanza|||0000-0003-1490-0678, López, Juan A., Jiménez, Santiago, Simiele, Adriana, Vidriales, Belen, González, Bernardo J., Burgaleta, Carmen, Hernández Rivas, José A., Córdoba Mascuñano, Raúl, Bautista, Guiomar, Perez Simon, José A., De la Fuente, Adolfo, Rayón, Consolación, Troconiz, Iñaki|||0000-0003-3700-8658, Janda, Álvaro, Bosanquet, Andrew G., Hernández-Campo, Pilar, Primo, Daniel, López, Rocío, Liébana, Belen, Rojas, José L., Gorrochategui, Julián|||0000-0001-9262-8716, Sanz, Miguel A.|||0000-0003-1489-1177, Ballesteros, Joan
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:301838
Acceso en línea:https://ddd.uab.cat/record/301838
https://dx.doi.org/urn:doi:10.1016/j.clml.2013.11.006
Access Level:acceso abierto
Palabra clave:Chemosensitivity
Ex vivo
Flow cytometry
Individualized tumor response to testing
Personalized medicine
Descripción
Sumario: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) and potency (EC) 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. © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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