Antagonizing IAPs by SMAC Mimetic Birinapant Induces Apoptosis in AML Cells Including AML Stem/Progenitor Cells Alone and in Combination With Chemotherapy in vitro and in vivo

S376 Background: Individuals with congenital Trisomy 21 (+21) have an increased risk of developing acutemyeloid leukemia (AML). AMLwith +21 has traditionally been regarded as an intermediate risk prognosis. This study focuses on the biological and clinical features of patients (pts) with +21 AML. Methods: We analyzed pts treated at University of Texas MD Anderson Cancer Center (UTMDACC) between 1995 and 2011. Only pts that presented to UTMDACC at initial diagnosis with no prior therapy were included. Four cytogenetic groups were defined: +21 alone, +21 plus favorable cytogenetics, +21 plus intermediate cytogenetics and +21 plus unfavorable cytogenetics. Time to Progression (TTP) was defined as time from diagnosis to relapse or last follow up. Survival curves were calculated using Kaplan-Meier estimates. Results: A total of 90 pts harboring +21 aberrations at diagnosis were identified. Median age was 59 years (range, 18-88), 58% were male and 72 (80%) were of white race. At diagnosis, median white cell count was 4.6 (0.6-190) x 10/L, neutrophils 14 (0-86)%, hemoglobin 8.6 (3.3-13.4) g/dL, platelets 53 (4-395) x 10/L , peripheral blasts 17% (0-96), and bone marrow blasts 48% (0-97). FAB classification: M0-2 64%, M3 1%, M4-5 20%, M6 10%, M7 4%. Cytogenetics: +21 alone 11 (12%), plus favourable 7 (8%), plus intermediate 7 (85), plus unfavourable 65 (72%). Molecular mutations: NPM1 1/25 (4%), NRAS 4/53 (7%), CKIT 0/26 (0%), FLT3 4/49 (8%). Induction regimens included: Idarubicin+AraC-based 36%, fludarabine-based 24%, clofarabine-based 11%, topotecan-based 10%, hypomethylating-based 11%, and miscellaneous 8%. Overall Response Rate was 54%. Median TTP was 11 (2-130) months. Conclusions: Pts with AML harboring +21 have unique biological and clinical features. It rarely presents as a solely aberration and mostrly associates with complex cytoenetics. Further investigation is needed to determine its specific prognostic role.