Posted: Wednesday, May 27, 2020
Two single nucleotide polymorphisms (SNPs) have previously unrecognized clinical importance in their association with cytarabine toxicity in children being treated for acute myeloid leukemia (AML), according to research results in Clinical Cancer Research. Stella M. Davies, MBBS, PhD, of the University of Cincinnati College of Medicine, and colleagues explained that although cytarabine can effectively treat AML, it has associated toxicities in some patients, including treatment-related mortality.
The researchers set out to “determine the clinical relevance of SNPs identified through the use of HapMap lymphoblastoid cell-based models” to predict cytarabine toxicity in this disease. They found that of the 124 SNPs they tested in 348 children, “homozygous variant genotypes of rs2025501 and rs6661575 had increased in vitro cellular sensitivity to cytarabine and were associated with increased treatment-related mortality.”
Utilizing data and samples from Children’s Cancer Group study CCG 2961, the investigators reported that the rate of treatment-related mortality was notably increased in children with these genotypes who had received high-dose cytarabine (rs2025501, P = .0024; rs6661575, P = .0188). Dr. Davies and co-investigators also examined SNPs previously reported to impact treatment-related mortality in children with AML who received cytarabine, finding a significant association (P < .0001) with only variant genotype rs17202778 C/C.
The investigators believe their findings warrant further study in prospective AML trials. Because cytarabine sensitivity genotypes may predict treatment-related mortality, they “could be used to stratify to standard versus high-dose regimens” of the drug. In CCG 2961, treatment-related mortality was significant at 9% to 17%, depending on the treatment arm.
Disclosure: The study authors’ disclosure information can be found at aacrjournals.org.