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.
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.
Authors: Ana-Alicia López-Iglesias; Ana B Herrero; Marta Chesi; Laura San-Segundo; Lorena González-Méndez; Susana Hernández-García; Irena Misiewicz-Krzeminska; Dalia Quwaider; Montserrat Martín-Sánchez; Daniel Primo; Teresa Paíno; P Leif Bergsagel; Thomas Mehrling; Marcos González-Díaz; Jesús F San-Miguel; María-Victoria Mateos; Norma C Gutiérrez; Mercedes Garayoa; Enrique M Ocio Journal: J Hematol Oncol Date: 2017-06-20 Impact factor: 17.388
Authors: Chengyin Min; Nathan Moore; Jeffrey R Shearstone; Steven N Quayle; Pengyu Huang; John H van Duzer; Matthew B Jarpe; Simon S Jones; Min Yang Journal: PLoS One Date: 2017-01-06 Impact factor: 3.240
Authors: Juan Eduardo Megías-Vericat; David Martínez-Cuadrón; Joaquín Martínez López; Juan Miguel Bergua; Mar Tormo; Josefina Serrano; Ataulfo González; Jaime Pérez de Oteyza; Susana Vives; Belén Vidriales; Pilar Herrera; Juan Antonio Vera; Aurelio López Martínez; Adolfo de la Fuente; Ma Lourdes Amador; José-Ángel Hernández-Rivas; Ma Ángeles Fernández; Carlos Javier Cerveró; Daniel Morillo; Pilar Hernández Campo; Julián Gorrochategui; Daniel Primo; José Luis Rojas; Margarita Guenova; Joan Ballesteros; Miguel Sanz; Pau Montesinos Journal: Mediterr J Hematol Infect Dis Date: 2019-03-01 Impact factor: 2.576