Pharmacological profiles of acute myeloid leukemia treatments in patient samples by automated flow cytometry
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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2014 |
| Country: | España |
| Institution: | Universitat Autònoma de Barcelona |
| Repository: | Dipòsit Digital de Documents de la UAB |
| Language: | English |
| OAI Identifier: | oai:ddd.uab.cat:301838 |
| Online Access: | https://ddd.uab.cat/record/301838 https://dx.doi.org/urn:doi:10.1016/j.clml.2013.11.006 |
| Access Level: | Open access |
| Keyword: | Chemosensitivity Ex vivo Flow cytometry Individualized tumor response to testing Personalized medicine |
| Summary: | 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) and potency (EC) 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. © 2014 The Authors. Published by Elsevier Inc. All rights reserved. |
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