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

Ronan T Swords, Diana Azzam, Hassan Al-Ali, Ines Lohse, Claude Henry Volmar, Justin Watts, Aymee Perez, Ana Rodriguez, Fernando Vargas, Roy Elias, Francisco Vega, Arthur Z Zelent, Shaun P Brothers, Taher Abbasi, Jonathan Trent, Shaukat Rangwala, Yehuda Deutsch, Eibhlin Conneally, Leylah Drusbosky, Christopher R. CogleClaes R Wahlestedt

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 72 h 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.

Original languageEnglish (US)
Pages (from-to)34-41
Number of pages8
JournalLeukemia Research
Volume64
DOIs
StatePublished - Jan 1 2018

Fingerprint

Acute Myeloid Leukemia
Pharmaceutical Preparations
Precision Medicine
Therapeutics
Physicians
Survival
Clinical Decision-Making
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Ex-vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia : A pilot study. / Swords, Ronan T; Azzam, Diana; Al-Ali, Hassan; Lohse, Ines; Volmar, Claude Henry; Watts, Justin; Perez, Aymee; Rodriguez, Ana; Vargas, Fernando; Elias, Roy; Vega, Francisco; Zelent, Arthur Z; Brothers, Shaun P; Abbasi, Taher; Trent, Jonathan; Rangwala, Shaukat; Deutsch, Yehuda; Conneally, Eibhlin; Drusbosky, Leylah; Cogle, Christopher R.; Wahlestedt, Claes R.

In: Leukemia Research, Vol. 64, 01.01.2018, p. 34-41.

Research output: Contribution to journalArticle

Swords, RT, Azzam, D, Al-Ali, H, Lohse, I, Volmar, CH, Watts, J, Perez, A, Rodriguez, A, Vargas, F, Elias, R, Vega, F, Zelent, AZ, Brothers, SP, Abbasi, T, Trent, J, Rangwala, S, Deutsch, Y, Conneally, E, Drusbosky, L, Cogle, CR & Wahlestedt, CR 2018, 'Ex-vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia: A pilot study', Leukemia Research, vol. 64, pp. 34-41. https://doi.org/10.1016/j.leukres.2017.11.008
Swords, Ronan T ; Azzam, Diana ; Al-Ali, Hassan ; Lohse, Ines ; Volmar, Claude Henry ; Watts, Justin ; Perez, Aymee ; Rodriguez, Ana ; Vargas, Fernando ; Elias, Roy ; Vega, Francisco ; Zelent, Arthur Z ; Brothers, Shaun P ; Abbasi, Taher ; Trent, Jonathan ; Rangwala, Shaukat ; Deutsch, Yehuda ; Conneally, Eibhlin ; Drusbosky, Leylah ; Cogle, Christopher R. ; Wahlestedt, Claes R. / Ex-vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia : A pilot study. In: Leukemia Research. 2018 ; Vol. 64. pp. 34-41.
@article{ca689529ef37490a862ff9f3e011f50d,
title = "Ex-vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia: A pilot study",
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 72 h 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",
author = "Swords, {Ronan T} and Diana Azzam and Hassan Al-Ali and Ines Lohse and Volmar, {Claude Henry} and Justin Watts and Aymee Perez and Ana Rodriguez and Fernando Vargas and Roy Elias and Francisco Vega and Zelent, {Arthur Z} and Brothers, {Shaun P} and Taher Abbasi and Jonathan Trent and Shaukat Rangwala and Yehuda Deutsch and Eibhlin Conneally and Leylah Drusbosky and Cogle, {Christopher R.} and Wahlestedt, {Claes R}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.leukres.2017.11.008",
language = "English (US)",
volume = "64",
pages = "34--41",
journal = "Leukemia Research",
issn = "0145-2126",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Ex-vivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia

T2 - A pilot study

AU - Swords, Ronan T

AU - Azzam, Diana

AU - Al-Ali, Hassan

AU - Lohse, Ines

AU - Volmar, Claude Henry

AU - Watts, Justin

AU - Perez, Aymee

AU - Rodriguez, Ana

AU - Vargas, Fernando

AU - Elias, Roy

AU - Vega, Francisco

AU - Zelent, Arthur Z

AU - Brothers, Shaun P

AU - Abbasi, Taher

AU - Trent, Jonathan

AU - Rangwala, Shaukat

AU - Deutsch, Yehuda

AU - Conneally, Eibhlin

AU - Drusbosky, Leylah

AU - Cogle, Christopher R.

AU - Wahlestedt, Claes R

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 72 h 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.

AB - 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 72 h 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.

KW - Acute myeloid leukemia

KW - Ex-vivo sensitivity screening

KW - Precision medicine

UR - http://www.scopus.com/inward/record.url?scp=85034736092&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034736092&partnerID=8YFLogxK

U2 - 10.1016/j.leukres.2017.11.008

DO - 10.1016/j.leukres.2017.11.008

M3 - Article

C2 - 29175379

AN - SCOPUS:85034736092

VL - 64

SP - 34

EP - 41

JO - Leukemia Research

JF - Leukemia Research

SN - 0145-2126

ER -