Portal de Periódicos da CAPES

Pharmacological Profiles of Acute Myeloid Leukemia Treatments in Patient Samples by Automated Flow Cytometry: A Bridge to Individualized Medicine

2013; Elsevier BV; Volume: 14; Issue: 4 Linguagem: Inglês

10.1016/j.clml.2013.11.006

2152-2650

Teresa Bennett, Pau Montesinos, Federico Moscardó, David Martínez‐Cuadrón, Joaquín Martínez‐López, Jorge Sierra, Raimundo García, Jaime Pérez de Oteyza, Pascual Fernández, Josefina Serrano, Ángeles Fernández, Pilar Herrera, Ataulfo González, Concepción Bethancourt, Gabriela Rodríguez‐Macías, Arancha Alonso, Juan Antonio Vera, Begoña Navas, Esperanza Lavilla, Juan Antonio López, Santiago Jiménez, Adriana Simiele, María‐Belén Vidriales, Bernardo Javier González González, Carmen Burgaleta, José‐Ángel Hernández‐Rivas, Raúl Córdoba Mascuñano, Guiomar Bautista, José Antonio Pérez‐Simón, Adolfo de la Fuente, Consolación Rayón, Iñaki F. Trocóniz, Álvaro Janda, Andrew G. Bosanquet, Pilar Hernández-Campo, Daniel Primo, Rocío López, Belén Liébana, José Luis Vázquez Rojas, Julián Gorrochategui, Miguel Á. Sanz, Joan Ballesteros,

Acute Lymphoblastic Leukemia research

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.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.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.We hypothesize that the use of the individual patient ex vivo pharmacological profiles may help to guide a personalized treatment selection.