The 340 de novo Acute Myeloid Leukemia (AML) patients (ages 1 month to 21 years) were enrolled in COG-AAML03P1 (<a href="https://clinicaltrials.gov/search?term=NCT00070174">NCT00070174</a>). Everyone received standard chemotherapy regimen of ara-C, daunorubicin and etoposide (ADE) with addition of one 3 mg/m2 dose of Gemtuzumab Ozogamicin (GO) in induction 1 as well as in intensification II phase. The 1022 de novo AML patients (ages 0–30 years) were enrolled in COG-AAML0531 (<a href="https://clinicaltrials.gov/search?term=NCT01407757">NCT01407757</a>). They were randomly assigned to receive either the standard ADE regimen (ADE arm, n = 511) or with the addition of one 3 mg/m2 dose of GO, during induction I as well as intensification II phase (ADE+GO arm, n = 511). Detailed study design, treatment regimen, and clinical outcomes of these two trials have been previously published (Cooper TM, Franklin J, Gerbing RB, et al., <a href="https://pubmed.ncbi.nlm.nih.gov/21766293/">PMID:21766293</a> and Gamis AS, Alonzo TA, Meshinchi S, et al., <a href="https://pubmed.ncbi.nlm.nih.gov/25092781/">PMID:25092781</a>). The current study used genomic DNA from 1,225 pediatric patients treated in these two trials with 470 patients treated with standard chemotherapy in <a href="https://clinicaltrials.gov/study/NCT01407757">COG-AAML0531</a> (ADE arm) and 755 patients treated with addition of GO to standard therapy in <a href="https://clinicaltrials.gov/search?term=NCT00070174">COG-AAML03P1</a> and <a href="https://clinicaltrials.gov/study/NCT01407757">COG-AAML0531</a> trials (ADE+GO arm). The 132 SNPs in 42 genes within DNA-damage repair (DDR) pathways or genes implicated in mediating calicheamicin were selected for genotyping. These SNPs were genotyped using the Sequenom platform at the <a href="https://genomics.umn.edu/">Biomedical Genomics Center, University of Minnesota</a>. All SNPs had a call rate of more than 0.98 and were in accordance with the Hardy–Weinberg equilibrium. These genotypes were used to test for association with clinical endpoints as defined in the <a href="https://clinicaltrials.gov/search?term=NCT00070174">COG-AAML03P1</a> and <a href="https://clinicaltrials.gov/study/NCT01407757">COG-AAML0531</a> trials.

Impact of Genetic Variation on Response to GO Therapy in COG-AML Trials AAML03P1 and AAML0531

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