Ex Vivo Drug Sensitivity Correlates with Clinical Response and Supports Personalized Therapy in Pediatric AML

Authors

Debbie C Strachan
Christine J Gu
Ryosuke Kita
Erica K Anderson
Michelle A Richardson
George Yam
Graham Pimm
Jordan Roselli
Alyssa Schweickert
Maci Terrell
Raushan Rashid
Alan K Gonzalez
Hailey H Oviedo
Michelle C Alozie
Tamilini Ilangovan
Andrea N Marcogliese
Hiroomi Tada
Marianne T Santaguida
Alexandra M Stevens

Language

English

Publication Date

12-18-2022

Journal

Cancers

DOI

10.3390/cancers14246240

PMID

36551725

PMCID

PMC9777060

PubMedCentral® Posted Date

12-18-2022

PubMedCentral® Full Text Version

Post-print

Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease that accounts for ~20% of all childhood leukemias, and more than 40% of children with AML relapse within three years of diagnosis. Although recent efforts have focused on developing a precise medicine-based approach towards treating AML in adults, there remains a critical gap in therapies designed specifically for children. Here, we present ex vivo drug sensitivity profiles for children with de novo AML using an automated flow cytometry platform. Fresh diagnostic blood or bone marrow aspirate samples were screened for sensitivity in response to 78 dose conditions by measuring the reduction in leukemic blasts relative to the control. In pediatric patients treated with conventional chemotherapy, comprising cytarabine, daunorubicin and etoposide (ADE), ex vivo drug sensitivity results correlated with minimal residual disease (r = 0.63) and one year relapse-free survival (r = 0.70; AUROC = 0.94). In the de novo ADE analysis cohort of 13 patients, AML cells showed greater sensitivity to bortezomib/panobinostat compared with ADE, and comparable sensitivity between venetoclax/azacitidine and ADE ex vivo. Two patients showed a differential response between ADE and bortezomib/panobinostat, thus supporting the incorporation of ex vivo drug sensitivity testing in clinical trials to further evaluate the predictive utility of this platform in children with AML.

Keywords

pediatric acute myeloid leukemia, precision medicine, flow cytometry, ex vivo drug sensitivity, combination therapy, personalized medicine, ADE, bortezomib, panobinostat

Published Open-Access

yes

Recommended Citation

Strachan, Debbie C; Gu, Christine J; Kita, Ryosuke; et al., "Ex Vivo Drug Sensitivity Correlates with Clinical Response and Supports Personalized Therapy in Pediatric AML" (2022). Faculty and Staff Publications. 5626.
https://digitalcommons.library.tmc.edu/baylor_docs/5626