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


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.


CONCLUSIONS
We hypothesize that the use of the individual patient ex vivo pharmacological profiles may help to guide a personalized treatment selection.
Vivia Biotech, Malaga, Spain.
Teresa A
TA
Bennett
Hospital Universitario La Fe, Valencia, Spain.
Pau
P
Montesinos
Hospital Universitario La Fe, Valencia, Spain.
Federico
F
Moscardo
Hospital Universitario La Fe, Valencia, Spain.
David
D
Martinez-Cuadron
Hospital Universitario 12 de Octubre, Madrid, Spain.
Joaquin
J
Martinez
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Jorge
J
Sierra
Hospital Universitario General de Castellón, Castellón, Spain.
Raimundo
R
García
Hospital de Madrid Norte Sanchinarro, Madrid, Spain.
Jaime Perez
JP
de Oteyza
Hospital General Universitario de Alicante, Alicante, Spain.
Pascual
P
Fernandez
Hospital Universitario Reina Sofía, Córdoba, Spain.
Josefina
J
Serrano
Hospital Xeral Cies, Vigo, Spain.
Angeles
A
Fernandez
Hospital Universitario Ramon y Cajal, Madrid, Spain.
Pilar
P
Herrera
Hospital Clínico San Carlos, Madrid, Spain.
Ataulfo
A
Gonzalez
Hospital Regional Universitario Carlos Haya, Málaga, Spain.
Concepcion
C
Bethancourt
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Gabriela
G
Rodriguez-Macias
Hospital Quirón Madrid, Madrid, Spain.
Arancha
A
Alonso
Hospital Universitario Virgen Macarena, Sevilla, Spain.
Juan A
JA
Vera
Hospital Moncloa, Madrid, Spain.
Begoña
B
Navas
Hospital Universitario Lucus Augusti, Lugo, Spain.
Esperanza
E
Lavilla
Complejo Hospitalario de Jaén, Jaén, Spain.
Juan A
JA
Lopez
Hospital Universitario de Gran Canaria Doctor Negrin, Las Palmas, Spain.
Santiago
S
Jimenez
Hospital Povisa, Pontevedra, Spain.
Adriana
A
Simiele
Hospital Clinico Universitario de Salamanca, Salamanca, Spain.
Belen
B
Vidriales
Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
Bernardo J
BJ
Gonzalez
Hospital Principe de Asturias, Madrid, Spain.
Carmen
C
Burgaleta
Hospital Universitario Infanta Leonor, Madrid, Spain.
Jose A
JA
Hernandez Rivas
Hospital Infanta Sofia, Madrid, Spain.
Raul Cordoba
RC
Mascuñano
Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
Guiomar
G
Bautista
Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Jose A
JA
Perez Simon
MD Anderson Madrid, Madrid, Spain.
Adolfo de la
Ade L
Fuente
Hospital Universitario Central de Asturias, Oviedo, Spain.
Consolación
C
Rayón
Universidad de Navarra, Pamplona, Spain.
Iñaki F
IF
Troconiz
Universidad de Navarra, Pamplona, Spain.
Alvaro
A
Janda
TEST Laboratories Ltd, Bath, UK.
Andrew G
AG
Bosanquet
Vivia Biotech, Malaga, Spain.
Pilar
P
Hernandez-Campo
Vivia Biotech, Malaga, Spain.
Daniel
D
Primo
Vivia Biotech, Malaga, Spain.
Rocio
R
Lopez
Vivia Biotech, Malaga, Spain.
Belen
B
Liebana
Vivia Biotech, Malaga, Spain.
Jose L
JL
Rojas
Vivia Biotech, Malaga, Spain.
Julian
J
Gorrochategui
Hospital Universitario La Fe, Valencia, Spain.
Miguel A
MA
Sanz
Vivia Biotech, Malaga, Spain. Electronic address: jballesteros@viviabiotech.com.
Joan
J
Ballesteros
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D016896:Treatment Outcome
D000970:Antineoplastic Agents
Chemosensitivity; Ex vivo; Flow cytometry; Individualized tumor response to testing; Personalized medicine