AI Article Synopsis

  • Researchers evaluated the pharmacology of single drugs and combinations using bone marrow samples from 125 acute myeloid leukemia patients with an advanced automated platform.
  • The study utilized whole blood for drug testing and analyzed the effectiveness in depleting leukemic cells over a 48-hour incubation period.
  • Results showed significant variability in patient responses to drug treatments, suggesting that personalized ex vivo drug profiles could enhance treatment selection for individuals.

Article Abstract

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.

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Source
http://dx.doi.org/10.1016/j.clml.2013.11.006DOI Listing

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