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

Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):305-18. doi: 10.1016/j.clml.2013.11.006. Epub 2013 Nov 15.


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.

Keywords: Chemosensitivity; Ex vivo; Flow cytometry; Individualized tumor response to testing; Personalized medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / pathology
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Monitoring
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Female
  • Flow Cytometry
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Middle Aged
  • Precision Medicine
  • Treatment Outcome


  • Antineoplastic Agents