6597 Background: FLT3 mutations occur in one third of acute myeloid leukemia (AML) patients (pts) and predict poor outcome. The incidence and impact of FLT3 in MDS/ CMML is unknown. Methods: We conducted a retrospective review at MDACC to identify FAB MDS/ CMML pts with FLT3 mutations at diagnosis. Results: From 1996 to 2010; 2052 MDS/ CMML pts had mutation analysis. 45 (2.2%) had FLT3 mutations (internal tandem duplication-ITD or D835) at diagnosis. 29 pts had MDS and 16 had CMML. Median (Med) age was 64 years (21 to 83) and 69% were males. FAB groups: 3 pts with refractory anemia (RA), 11 pts with refractory anemia-excess blasts (RAEB), 18 pts with refractory anemia-excess blasts in transformation (RAEB-T) and 13 pts with CMML. IPSS: 3 in Low (7%), 16 in Int-1 (36%), 11 in Int-2 (24%), and 15 in High (33%). Med white count, hemoglobin, platelet count and marrow blast percent at diagnosis were 5.2 x 109/l (1.2 to 211), 10.0 g/l (6.8 to 14.9), 78 x 109/l (8 to 429), and 14% (1 to 28), respectively. FLT3 ITD and FLT3 D835 mutations were present in 32 (71%) and 13 pts (29%), respectively. Karyotype was diploid in 30 (66%); -5/-7 in 5 (11%), 11q in 1 (2%), and others in 9 pts (19%). All 5 pts with -5/ -7 had the ITD mutation. Concurrent mutations were identified in RAS, NPM1 and C-Kit in 6 (13%), 3 (7%) and 1 (2%) pt, respectively. Med overall survival (OS) for FLT3 pts was 15 months compared to 17 months for non FLT3 pts (P=0.9). 18 pts had RAEB-T: 13 (72%) received AraC-based therapy and 3 (17%) received hypomethylating therapy (HMT) with complete remission (CR) in 14 pts (78%). 14 pts had RA/ RAEB: 5 (36%) received AraC-based therapy and 7 (50%) received HMT with CR in 5 (37%) and hematological improvement (HI) in 4 (28%). 13 pts had CMML: 4 (31%) received AraC-based therapy and 6 (46%) received HMT with CR in 3 (23%) and HI in 3 (23%). Repeat FLT3 was available on 16 pts achieving any response and was absent/ decreased in 14 (88%), stable in 1 (6%) and increased in 1 (6%). Notably, the 14 pts with absent/ decreased FLT3 had med OS of 27 months versus 12 months for remaining group (P=0.004). Conclusions: FLT3 occurs in MDS/ CMML at a lower frequency than AML and does not predict poor outcome. Pts who achieve absent/ decreased FLT3 seem to have significantly improved overall survival.