Dataset Information

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 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.

SUBMITTER: Swords RT

PROVIDER: S-EPMC5756519 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Swords Ronan T RT Azzam Diana D Al-Ali Hassan H Lohse Ines I Volmar Claude-Henry CH Watts Justin M JM Perez Aymee A Rodriguez Ana A Vargas Fernando F Elias Roy R Vega Francisco F Zelent Arthur A Brothers Shaun P SP Abbasi Taher T Trent Jonathan J Rangwala Shaukat S Deutsch Yehuda Y Conneally Eibhlin E Drusbosky Leylah L Cogle Christopher R CR Wahlestedt Claes C

Leukemia research 20171111

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 ...[more]

PMID: 29175379

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Project description:BackgroundBone marrow (BM) evaluation is the de facto standard for diagnosis, molecular analysis, risk stratification, and therapy response assessment in acute myeloid leukemia (AML), but in patients with a high number of circulating blast cells, the peripheral blood (PB) sample could provide similar information as BM. However, there is no large-scale molecular study comparing the two specimens in terms of their gene expression profiles, cellular heterogeneities, and ex-vivo drug sensitivity.MethodologyWe used (i) the BEAT-AML cohort each with detailed molecular data; (ii) cell-type deconvolution to estimate leukemic and immune cell proportions between specimen types; (iii) differential expression (DE) and drug-cell type association analysis; and (iv) logistic regression models to assess the association between induction therapy response, cell-type composition and first-line drug treatment.ResultsResults: We identified 207 patients having BM and 116 patients having PB samples. There was a total of 1271 DE genes (false discovery rate < 0.05) between BM and PB; the top enriched pathways in terms of DE genes belong to the immune system pathways. Aggregated ex-vivo drug response profiles from the two specimens were largely similar, as were the cellular components, except for the GMP-like cell type (17% in BM vs. 5% in PB, p-value = 2 × 10-7). Among the specimen-specific results, the GMP-like subtype was associated with multiple drug resistance in BM and the ProMono-like subtype in PB. Several cell types were associated with the response to induction therapy, but the impact of specimen type on the interaction of cell type and cytarabine-associated induction therapy was not statistically significant for most cell types.ResultsConclusions: Even though there are molecular and cellular differences between BM and PB samples, they show many similarities in ex-vivo drug response profiles, indicating the clinical utility of the substantially less-invasive PB samples.

Dataset Information

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

Publications

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

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