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

Autor: Strachan DC; Notable Labs, Foster City, CA 94404, USA., Gu CJ; Notable Labs, Foster City, CA 94404, USA., Kita R; Notable Labs, Foster City, CA 94404, USA., Anderson EK; Notable Labs, Foster City, CA 94404, USA., Richardson MA; Notable Labs, Foster City, CA 94404, USA., Yam G; Notable Labs, Foster City, CA 94404, USA., Pimm G; Notable Labs, Foster City, CA 94404, USA., Roselli J; Notable Labs, Foster City, CA 94404, USA., Schweickert A; Notable Labs, Foster City, CA 94404, USA., Terrell M; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA., Rashid R; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA., Gonzalez AK; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA., Oviedo HH; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA., Alozie MC; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA., Ilangovan T; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA., Marcogliese AN; Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA., Tada H; Notable Labs, Foster City, CA 94404, USA., Santaguida MT; Notable Labs, Foster City, CA 94404, USA., Stevens AM; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Dec 18; Vol. 14 (24). Date of Electronic Publication: 2022 Dec 18.
DOI: 10.3390/cancers14246240
Abstrakt: 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.
Databáze: MEDLINE
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