Genomic Variants of Cytarabine Sensitivity Associated with Treatment-Related Mortality in Pediatric AML: A Report from the Children’s Oncology Group

Phillips CL, Lane A, Gerbing RB, Alonzo TA, Wilkey A, Radloff G, Lange B, Gamazon ER, Dolan ME, Davies SM. Genomic Variants of Cytarabine Sensitivity Associated with Treatment-Related Mortality in Pediatric AML: A Report from the Children’s Oncology Group. Clin Cancer Res. 2020 Jun 15;26(12):2891-2897. doi: 10.1158/1078-0432.CCR-19-3117. Epub 2020 Mar 2. PubMed PMID: 32122921; PubMed Central PMCID: PMC7722896.

Cytarabine is an effective treatment for AML with associated toxicities including treatment related mortality (TRM). The purpose is to determine the clinical relevance of single-nucleotide polymorphisms (SNPs) identified through the use of HapMap lymphoblastoid cell-based models, in predicting cytarabine response and toxicity in AML. We tested clinical significance of SNPs associated with cytarabine sensitivity in children with AML treated on Children’s Oncology Group regimens (CCG 2941/2961). Endpoints included overall survival (OS), event free survival (EFS) and TRM. Patients who received bone marrow transplant were excluded. We tested 124 SNPs associated with cytarabine sensitivity in HapMap cell lines in 348 children to determine if any associated with treatment outcomes. In addition, we tested five SNPs previously associated with TRM in children with AML in our independent data set of 385 children.