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

Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531.

AAML03P1, a pilot study of the safety of gemtuzumab ozogamicin in combination with chemotherapy for newly diagnosed childhood acute myeloid leukemia

Genetic variation in DNA damage response pathway and response to Gemtuzumab Ozogamicin in pediatric AML: a report from the Children's Oncology Group.