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Polygenic score helps guide choice of chemotherapy for pediatric AML | Health and fitness


TUESDAY, Feb. 1, 2022 (HealthDay News) — A polygenic score derived from pharmacogenomic evaluation of the cytarabine (ara-C) pathway may help personalize treatment for pediatric patients with acute myeloid leukemia (AML), according to a study published online January 18 in the Journal of Clinical Oncology.

Abdelrahman H. Elsayed, Ph.D., of the University of Florida at Gainesville, and colleagues analyzed single nucleotide polymorphisms (SNPs) in 166 patients from the multicenter AML02 trial. The 10-SNP Ara-C_SNP (ACS10) score was developed via multi-SNP predictive modeling using the main SNPs predictive of minimal residual disease and event-free survival (EFS) from the AML02 cohort and four previously associated SNPs to ara-C triphosphate levels in a separate assay. In each clinical trial arm, ACS10 was assessed for association with outcomes: the standard low-dose ara-C (LDAC, 91 patients) and increased high-dose ara-C (HDAC, 75 patients) of AML02 and the standard ara-C, daunorubicin and etoposide (ADE) (465 patients) and the augmented ADE + gemtuzumab ozogamicin (GO; 466 patients) arms of the AAML0531 trial.

The researchers found that EFS and overall survival were significantly worse in the low ACS10 group compared to the high ACS10 group in the standard LDAC arm of the AML02 cohort (hazard ratios, 2.81 and 2.98, respectively ). These results were validated in the standard ADE arm of AAML0531, with worse results observed in the low versus high AUC10 groups (relative risks, 1.35 and 1.64, respectively). EFS and overall survival did not differ between the low and high ACS10 score groups in the augmented arms (AML02-HDAC and AAML0531-ADE+GO).

“Our comprehensive approach not only provides a single ACS10 score of prognostic significance that can predict poor outcome in AML, but suggests that alternative treatment strategies with either a high dose of ara-C or the addition of GO are more appropriate strategies for patients with low ACS10 score,” the authors write.

Several authors disclosed financial ties to the pharmaceutical industry; three authors disclosed pending patents related to the subject of the study.