Amplification Of Aml1 Does Not Impact Early Outcome Of Children With Acute Lymphoblastic Leukemia (All) Treated With Risk-Directed Chemotherapy: A Report From The Children'S Oncology Group (Cog)

Abstract Abstract 2598 Poster Board II-574 Amplification of a region of chromosome 21 (which includes the AML1 (RUNX1) locus (amp(AML1)) has been reported as a recurring abnormality in pediatric ALL that is associated with increased age (median 9 years), a low white blood cell (WBC) count, and a poor outcome. (Moorman et al Blood 109:2327, 2007; Attarbaschi et al JCO 26:3046, 2008). Early results in these studies indicated approximately a 75% event-free survival (EFS) at 2 years. Amp(AML1) can be reliably detected only by fluorescence in situ hybridization (FISH), and can be recognized when blasts are tested by FISH for the presence of the TEL(ETV6)/RUNX1 translocation. We reviewed the clinical features and outcome of children with ALL and amp(AML1) treated on current generation COG trials from 2003–2009 (median follow up 1.2 years, range: 0.03–3.83 yrs). Diagnosis of amp(AML1) required at least 5 copies of AML1, with 4 copies on a single chromosome. Children with B-precursor ALL received a 3- or 4-drug induction based on NCI risk group, with post-induction therapy based on further risk stratification variables measured during the first month of induction. Patients with a poor early response to therapy (day 15 bone marrow (BM) with >5% blasts or day 29 BM minimal residual disease (MRD) >0.1%) were non-randomly assigned to receive augmented chemotherapy. Treatment was not altered for patients with amp(AML1). Since June 1, 2007, ETV6/RUNX1 FISH was required on all children enrolled on this study. From Dec 29, 2003 to June 1, 2007, FISH was not required on all patients so ascertainment of amp(AML1) may not be complete. There were 89/5470 (1.6%) children with B-precursor ALL in whom amp(AML1) was detected. Similar to previous reports (see Table), their median age was 9.1 years, median WBC was 4.5×109/l; and 55.1% were female, a higher proportion than previously reported (43%–48%). While the distribution of day 29 MRD by flow cytometry was different, NCI risk group distribution, 2-year EFS and overall survival (OS) were similar between patients with and without amp(AML1). Of the 10 events that occurred in patients with amp(AML1), there were 3 induction failures, 3 induction deaths, and 4 relapses. Thus, early response to risk-adapted therapy is similar in children with and without amp(AML1). We conclude that, using risk-adapted therapy, children with ALL and amp(AML1) have an early outcome similar to those lacking this feature; however, longer follow up is needed to determine the full impact of amp(AML1) on eventual outcome. Disclosures: No relevant conflicts of interest to declare.