Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Abstract 2610</jats:p>
<jats:p>Poster Board II-586</jats:p>
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<jats:p>Cytarabine is a key chemotherapeutic agent in the treatment of acute myeloid leukemia (AML). We have taken a pathway based candidate gene approach to select variants likely to be critical to cytarabine metabolism. Single non-synonymous nucleotide polymorphisms and polymorphisms located in promoter regions of genes involved in cytarabine metabolism, with known frequencies > 5% in the Caucasian population were identified. We genotyped 479 children treated for de novo AML on the Children's Cancer Group (CCG) 2941 and 2961 protocols for these polymorphisms. All patients received intensively timed induction therapy with IDA-DCTER (idarubicin, dexamethasone, Ara-C (800 mg/m2 total dose), thioguanine, etoposide and daunomycin) given on days 0 to 3 followed by DCTER given on days 10 to 13. On recovery of ANC and platelet counts, patients were randomized to consolidation therapy with Regimen A: a further course of IDA-DCTER/DCTER or Regimen B: IDA-FLAG (idarubicin, fludarabine, Ara-C (7590 mg/m2 total dose Ara-C) and G-CSF). Patients with a matched family donor received intensification with allogeneic transplant; all others received a single course of high dose Ara-C (24,000 mg/m2 total dose) and L-asparaginase. There were no significant associations between genotypes and clinical characteristics of leukemia, although polymorphism frequencies did differ significantly by race. Significant associations with outcome of therapy in a multivariate analysis adjusted for race are listed below:</jats:p>
<jats:p>The nucleoside transporter gene hENT promoter polymorphism rs747199 influenced 5 year overall survival (OS) from study entry (46 ± 6% in G/G cases versus 58 ± 9% in other patients (p=0.039). Similarly, 5 year OS from end of two courses was improved in children with a C/C genotype at rs693955 (OS 66 ± 7% vs. 54 ± 11%, p= 0.058). No significant differences were found in disease free survival, relapse rate (RR), or treatment related mortality for these variants. Nucleoside transporter polymorphisms may play a critical role in modulating cytarabine transport and influence the outcome of therapy for AML in children.</jats:p>
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<jats:title>Disclosures:</jats:title>
<jats:p>No relevant conflicts of interest to declare.</jats:p>
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