ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Genomic Variants of Cytarabine Sensitivity Associated with Treatment-Related Mortality in Pediatric AML: A Report from the Children's Oncology Group.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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10 authors at 6 institutions in 3 countries.
Funding
Abstract
purposeCytarabine is an effective treatment for AML with associated toxicities including treatment related mortality (TRM). The purpose is to determine the clinical relevance of SNPs identified through the use of HapMap lymphoblastoid cell-based models, in predicting cytarabine response and toxicity in AML. EXPERIMENTAL
designWe 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 whether any associated with treatment outcomes. In addition, we tested five SNPs previously associated with TRM in children with AML in our independent dataset of 385 children.
resultsHomozygous variant genotypes of rs2025501 and rs6661575 had increased
conclusionsWe report clinical importance of two SNPs not previously associated with cytarabine toxicity. Moreover, we confirm that SNP rs17202778 significantly impacts TRM in pediatric AML. Cytarabine sensitivity genotypes may predict TRM and could be used to stratify to standard versus high-dose cytarabine regimens, warranting further study in prospective AML trials.
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