Data from Clinical Significance of CD33 Nonsynonymous Single-Nucleotide Polymorphisms in Pediatric Patients with Acute Myeloid Leukemia Treated with Gemtuzumab-Ozogamicin–Containing Chemotherapy

Abstract

<div>Abstract<p><b>Purpose:</b> The purpose of this study was to evaluate clinical implications of CD33 single-nucleotide polymorphisms (SNP) in pediatric patients with acute myeloid leukemia (AML) treated with gemtuzumab-ozogamicin (GO)–based therapy.</p><p><b>Experimental Design:</b> We genotyped four CD33 SNPs: rs35112940 (G>A; Arg304Gly), rs12459419 (C>T; Ala14Val), rs2455069 (A>G; Arg69Gly), and rs1803254 (G>C; 3′UTR) in pediatric patients undergoing induction chemotherapy containing GO (COG-AAML03P1 trial; <i>n</i> = 242) or not containing GO (St. Jude AML02 trial; <i>n</i> = 172).</p><p><b>Results:</b> CD33 SNPs were correlated significantly with clinical characteristics and treatment outcome. The coding SNPs, rs35112940 and rs12459419, were significantly associated with clinical endpoints in COG-AAML03P1 but not in the St. Jude AML02 trial. Specifically, among white patients in COG-AAML03P1, the 3-year overall survival (OS) rate from remission was 84% ± 8% for those homozygous (GG) for rs35112940 versus 68% ± 15% for the other genotypes (<i>P</i> = 0.018); these patients also had a lower relapse risk and superior disease-free survival. Likewise, patients homozygous for variant allele (TT) for rs12459419 were more likely to have favorable risk disease than CC and CT genotypes (52% vs. 31%, <i>P</i> = 0.034) and significantly lower diagnostic blast CD33 expression than other genotypes (<i>P</i> < 0.001).</p><p><b>Conclusion:</b> Our data suggest that genetic variations in CD33 could impact clinical outcome of GO-based therapy in pediatric AMLs. <i>Clin Cancer Res; 19(6); 1620–7. ©2013 AACR</i>.</p></div>