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

Autores de IIS La Fe

• Pau Montesinos Fernández

  Autor

• Federico Moscardo Garcia

  Autor

• David Martínez Cuadrón

  Autor

• Jesus Antonio Martinez Dominguez

  Autor

• Rafael Garcia Dominguez

  Autor

• Pedro José Fernández Colom

  Autor

• Juan Serrano Gandia

  Autor

• Pablo Herrera Melian

  Autor

• Rafael López Andújar

  Autor

• Miguel Ángel Sanz Alonso

  Autor

Participantes ajenos a IIS La Fe

• Bennett TA
• Sierra J
• de Oteyza JP
• Fernandez A
• 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
• Hernandez Rivas JA
• Mascuñano RC
• Bautista G
• Perez Simon JA
• Fuente Ade L
• Rayón C
• Troconiz IF
• Janda A
• Bosanquet AG
• Hernandez-Campo P
• Primo D
• Liebana B
• Rojas JL
• Gorrochategui J
• Ballesteros J

Grupos

• Hematología y Hemoterapia

  

  Investigador Principal

  Javier De La Rubia Comos

• Hepatología experimental y Trasplante hepático

  Investigador Principal

  Laia Tolosa Pardo

• Medicina Fetal y Reproductiva

  

  Investigador Principal

  José Morales Roselló

Abstract

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.

Keywords

• Chemosensitivity; Ex vivo; Flow cytometry; Individualized tumor response to testing; Personalized medicine