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Leuk Res. 2018 Jan;64:34-41. doi: 10.1016/j.leukres.2017.11.008. Epub 2017 Nov 11.

Ex-vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia: A pilot study.

Author information

1
Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami, FL, United States.
2
Center for Therapeutic Innovation, Miller School of Medicine, University of Miami, Miami, FL, United States; Department of Psychiatry and Behavioral Sciences, United States; Molecular Therapeutics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami, FL, United States.
3
Molecular Therapeutics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami, FL, United States; Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL, United States; Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, United States; Peggy and Harold Katz Family Drug Discovery Center, Miller School of Medicine, University of Miami, Miami, FL, United States.
4
Cellworks Group Inc, San Jose, CA, United States.
5
MOgene LC, St Louis, MO, United States.
6
Memorial Health Care System, Miami, FL, United States.
7
Department of Hematology, St. James's Hospital, Dublin, Ireland.
8
Division of Hematology/Oncology, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, United States.
9
Center for Therapeutic Innovation, Miller School of Medicine, University of Miami, Miami, FL, United States; Department of Psychiatry and Behavioral Sciences, United States. Electronic address: cwahlestedt@med.miami.edu.

Abstract

A precision medicine approach is appealing for use in AML due to ease of access to tumor samples and the significant variability in the patients' response to treatment. Attempts to establish a precision medicine platform for AML, however, have been unsuccessful, at least in part due to the use of small compound panels and having relatively slow turn over rates, which restricts the scope of treatment and delays its onset. For this pilot study, we evaluated a cohort of 12 patients with refractory AML using an ex vivo drug sensitivity testing (DST) platform. Purified AML blasts were screened with a panel of 215 FDA-approved compounds and treatment response was evaluated after 72h of exposure. Drug sensitivity scoring was reported to the treating physician, and patients were then treated with either DST- or non-DST guided therapy. We observed survival benefit of DST-guided therapy as compared to the survival of patients treated according to physician recommendation. Three out of four DST-treated patients displayed treatment response, while all of the non-DST-guided patients progressed during treatment. DST rapidly and effectively provides personalized treatment recommendations for patients with refractory AML.

KEYWORDS:

Acute myeloid leukemia; Ex-vivo sensitivity screening; Precision medicine

PMID:
29175379
PMCID:
PMC5756519
[Available on 2019-01-01]
DOI:
10.1016/j.leukres.2017.11.008
[Indexed for MEDLINE]
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