The influence of cytidine deaminase -33delC polymorphism on treatment outcome with high-dose cytarabine in Chinese patients with relapsed acute myeloid leukaemia.

Abstract

Identification of biomarkers that could predict high-dose cytarabine (Ara-C) efficacy and toxicity is a key issue in individualized therapy. The aim of our study was to evaluate the influence of cytidine deaminase (CDA) single nucleotide polymorphisms (SNPs) -451G>A (rs532545), 435C>T (rs1048977) and -33delC (rs3215400) on treatment outcome in patients with relapsed acute myeloid leukaemia (AML) after high-dose Ara-C chemotherapy. In total, 173 patients with relapsed AML, treated with high-dose Ara-C chemotherapy, were genotyped for three polymorphisms in CDA gene using the allele-specific matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assays. Binary logistic regression was used to evaluate the influence of selected polymorphisms on tumour response and occurrence of treatment-related toxicity. The CC genotype at -33delC, a promoter polymorphism, increased the odds of overall response rate (odds ratio [OR]=5·125; 95% confidence intervals (CI)=2·446-10·74; P=0·0008) and grade ≥3 infection toxicity incidence rate (OR=3·572; 95% CI=1·68-7·594; P=0·003). In multivariable analysis, this polymorphism was a potential independent prognostic marker for the risk of overall response (P=0·011), but not grade ≥3 infection toxicity incidence rate (P=0·49). Two other polymorphisms, -451G>A and 435C>T, did not influence treatment outcome, including overall response rate, infection toxicity and nausea/vomiting, in patients with relapsed AML (P>0·05). The findings suggest that CDA -33delC variant might be a potential marker for predicting treatment outcome in Chinese patients with relapsed AML given high-dose cytarabine chemotherapy.