Pharmacological Profiles of Acute Myeloid Leukemia Treatments in Patient Samples by Automated Flow Cytometry: A Bridge to Individualized Medicine
Por:
Bennett, TA, Montesinos, P, Moscardo, F, Martinez-Cuadron, D, Martinez, J, Sierra, J, Garcia, R, De Oteyza, JP, Fernandez, P, Serrano, J, Fernandez, A, Herrera, P, Gonzalez, A, Bethancourt, C, Rodriguez-Macias, G, Alonso, A, Vera, JA, Navas, B, Lavilla, E, Lopez, JA, Jimenez, S, Simiele, A, Vidriales, B, Gonzalez, BJ, Burgaleta, C, Rivas, JAH, Mascunano, RC, Bautista, G, Simon, JA, de la Fuente, A, Rayon, C, Troconiz, IF, Janda, A, Bosanquet, AG, Hernandez-Campo, P, Primo, D, Lopez, R, Liebana, B, Rojas, JL, Gorrochategui, J, Sanz, MA, Ballesterosi, J
Publicada:
1 ago 2014
Resumen:
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.
Filiaciones:
Bennett, TA:
Vivia Biotech, Malaga, Spain
Montesinos, P:
Hosp Univ La Fe, Valencia, Spain
Moscardo, F:
Hosp Univ La Fe, Valencia, Spain
Hosp Univ 12 Octubre, Madrid, Spain
Martinez-Cuadron, D:
Hosp Univ La Fe, Valencia, Spain
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Garcia, R:
Hosp Univ Gen Castellon, Castellon de La Plana, Spain
De Oteyza, JP:
Hosp Madrid Norte Sanchinarro, Madrid, Spain
Fernandez, P:
Hosp Gen Univ Alicante, Alicante, Spain
Serrano, J:
Hosp Univ Reina Sofia, Cordoba, Spain
Fernandez, A:
Hosp Xetel Cies, Vigo, Spain
Herrera, P:
Hosp Univ Ramon & Cajal, Madrid, Spain
Gonzalez, A:
Hosp Clin San Carlos, Madrid, Spain
Bethancourt, C:
Hosp Reg Univ Carlos Haya, Malaga, Spain
Rodriguez-Macias, G:
Hosp Gen Univ Gregorio Maranon, Madrid, Spain
Alonso, A:
Hosp Quiron Madrid, Madrid, Spain
Navas, B:
Hosp Moncloa, Madrid, Spain
Lavilla, E:
Hosp Univ Lucus Augusti, Lugo, Spain
Lopez, JA:
Complejo Hosp Jaen, Jaen, Spain
Jimenez, S:
Hosp Univ Gran Canaria Doctor Negrin, Las Palmas Gran Canaria, Spain
Simiele, A:
Hosp Povisa, Pontevedra, Spain
Vidriales, B:
Univ Salamanca, Hosp Clin, E-37008 Salamanca, Spain
Gonzalez, BJ:
Hosp Univ Canarias, Tenerife, Spain
Burgaleta, C:
Hosp Principe Asturias, Madrid, Spain
Rivas, JAH:
Hosp Univ Infanta Leonor, Madrid, Spain
Mascunano, RC:
Hosp Infanta Sofia, Madrid, Spain
Bautista, G:
Hosp Univ Puerta Hierro Majadahonda, Madrid, Spain
Simon, JA:
Hosp Univ Virgen Rocio, Seville, Spain
de la Fuente, A:
MD Anderson Madrid, Madrid, Spain
Rayon, C:
Hosp Univ Cent Asturias, Oviedo, Spain
Troconiz, IF:
Univ Navarra, E-31080 Pamplona, Spain
Bosanquet, AG:
TEST Labs Ltd, Bath, Avon, England
Hernandez-Campo, P:
Vivia Biotech, Malaga, Spain
Primo, D:
Vivia Biotech, Malaga, Spain
Lopez, R:
Vivia Biotech, Malaga, Spain
Liebana, B:
Vivia Biotech, Malaga, Spain
Rojas, JL:
Vivia Biotech, Malaga, Spain
Gorrochategui, J:
Vivia Biotech, Malaga, Spain
Sanz, MA:
Hosp Univ La Fe, Valencia, Spain
Ballesterosi, J:
Vivia Biotech, Malaga, Spain
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