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Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid malignant disorders characterized by defects in hematopoietic progenitor differentiation and propensity for acute myelogenous leukemia (AML). Detectable DNMT3A, TET2, and ASXL1 mutations are not only associated with increased malignant conversion risk, but also with broad Cardiovascular (CV) risk. Indeed, clonal hematopoiesis of indetetermined potential (CHIP), is associated with parametric erythroid modifications (i.e., red cell distribution width [RDW] and mean corpuscular volume [MCV]) that occurs years before hematologic malignancy development, and correlates with current patient (pt) risk for CV disease. In this study, we seek to examine the predictive value of MCV in MDS pt diagnosed with and without CV disease. Methods: After IRB approval, 84 pt diagnosed with low-risk MDS (LR-MDS) were included for analysis. Median MCV was estimated in all LR-MDS patients to: (1) Examine overall survival (OS) in LR-MDS with and without CV disease; and (2) Detect differential OS in LR-MDS pt with and without CV disease according to baseline predictors such as hemoglobin, platelet count, RDW, platelet count, absolute neutrophil count (ANC), blast count, WHO classification and ferritin. CV was defined as the presence of one or combination of: (a) atherosclerotic hear disease demonstrated by cardiac catheterization; (2) Congestive Heart Failure (CHF); and (3) Peripheral Vascular Disease (PVD). Kaplan-Meier method was used to estimate overall survival (OS). Linear regression model was performed to adjust for multiple variable with potential impact on survival. Results: 44/84 (52.3%) and 40/84 (47.6%) pt were CV positive (pos) and CV negative (neg). Median age for CV disease (pos) and CV (neg) pt was 72 y (range 53-88) and 76 y (range 55-91), respectively, p=0.05. In LR-MDS pt with and without CV disease, median baseline hemoglobin (Hb), RDW, MCV, ferritin and blast count were not statistically different (p>0.05 for all groups). However, baseline ANC and platelet count were 2.1 K/uL vs 1.3 K/uL (p=0.01) and 109 K/uL vs 79 K/uL (p=0.01). Median MCV for all LR-MDS pt was 99 fL. Survival in LR-MDS CV (pos) pt with median MCV > or < 99 fL was 238 vs 634 d, respectively, p= 0.01 (HR 0.6114 95% CI 0.3486 to 1.073). LR-MDS CV (neg) had survival of 831 d vs 382 d (p= 0.3). In LR-MDS CV (pos), Hb at baseline was able to segregate 3 groups with differential survival 290, 659 and 1556 d, respectively, (Hb 10, p=0.1). However, different from CV (pos), hemoglobin segregated 3 distinct survival groups in CV (neg) 301, 430, 1877 d (Hb 10 p= 0.01). RDW as a continuous measure was not predictive for all patients (p=0.085), not for CV (pos) (p=0.908) but predictive for CV (neg) (p=0.012). R-IPSS was significant in all patients (p Conclusion: CV disease is well accepted predictor of poor survival among MDS pt. However, to our knowledge, previous studies examining predictors for outcome in LR-MDS pt diagnosed with CV has not been reported before. MCV is known erythroid parameter frequently abnormal in pt with MDS. Strong correlation between TET2, deregulated IL-1 beta and macrocytosis has been recently uncovered. In our studied population, median MCV specifically discriminated different survival in LR-MDS pt diagnosed with CV disease. Notably, Hb, RDW, platelet count, ferritin and WHO classification reproduced "unique" survival among LR-MDS pt with and without CV disease. Large studies are needed. However, this report emphasizes the need for differential management in LR-MDS CV (pos) vs CV (neg) pt. Disclosures No relevant conflicts of interest to declare.

Background: A number of studies have reported elevated incidence of 25-OH-vitamin D deficiency among patients with multiple myeloma (MM). Several studies have found association between vitamin D levels and factors associated with survival, including ISS stage at diagnosis. However, the impact of vitamin D deficiency on MM prognosis is not entirely clear. Also, in general, both the incidence and the impact of vitamin D deficiency differ substantially by race. Here, we investigate the impact of vitamin D deficiency on prognosis in a large and racially heterogenous patient population with MM in the Veterans Affairs (VA) system. Methods: We used the VA's nationwide Corporate Data Warehouse to identify patients diagnosed with symptomatic MM from 1999 to 2017. Various demographic and laboratory data was collected including age, race, 25-OH-vitamin D levels, and ISS stage at diagnosis as well as survival outcome data. Details of therapies received was also available which indicted similar access to all newer agents approved for myeloma for both African American (AA) and Caucasian patients. Results: We identified 15,717 patients diagnosed with MM (3353 AA and 9070 Caucasian), of whom 6675 had vitamin D measurements within 2 months of diagnosis (1959 AA and 4398 Caucasian). Median serum vitamin D levels were significantly lower among AA patients (21.8 ng/mL) than Caucasians (28.6 ng/mL; p We evaluated the ability of serum vitamin D level to predict overall survival (OS) in patients with MM using a cut-off of 20ng/mL. Patients with vitamin D deficiency ( The analyses were repeated for AA and Caucasian patients separately. Among AA patients, serum vitamin D was not a significant predictor of OS in univariate (P=0.5096) or multivariate analysis (P=0.6923), while it was still a strong predictor among Caucasian patients in both univariate (HR 1.38; P=0.0006) and multivariate analysis (HR 1.45; P=0.0048). Median OS is 3.54 years (95% CI 2.99-5.52; n=255) for AA patients with vitamin D deficiency and 3.95 years (3.25-5.35; n=296) with normal levels. Among Caucasians, median OS is 2.71 years (2.18-3.47; n=273) for deficient and 3.87 years (3.59-4.42; n=885) for normal. Kaplan-Meier plots (Fig. 1B and 1C) illustrate the observed OS curves for the two subgroups. Since levels of vitamin D were lower in AA patients, a lower cut-off of 10 ng/mL was also tested. Even using this lower cutoff, vitamin D deficiency was not a statistically significant predictor of OS in univariate (HR 1.33; P=0.0781) or multivariate analysis (HR 1.09; P=0.7039), though the number of AA patients with vitamin D Conclusions: Vitamin D deficiency is a significant predictor of survival among patients diagnosed with MM, even after accounting for race, age, and ISS stage. However, this relationship is only observed in Caucasian patients and not observed among AA patients. Studies are ongoing to evaluate impact of Vitamin D deficiency of disease presentation including bone disease as well as genetic characteristics. This investigation highlights the need to assess the underlying biological mechanism responsible for the observed impact of vitamin D deficiency across race in MM. Figure 1. Figure 1. Disclosures Yellapragada: Novartis: Employment; Celgene: Research Funding; Takeda: Research Funding. Munshi:OncoPep: Other: Board of director.

Background : Low riskMyelodysplastic Syndrome (LR-MDS) is a cytogenetic, epigenetic and immunologically heterogeneous group of disorders associated with refractory anemia (RA) in about 75% of the cases. Conventionally, blood transfusion and Erythropoiesis Stimulating Agents (ESAs) are indicated. Azanucleosides provide clinical benefit in about 20-25% of patients (pts) with ESA refractory disease highlighting the need for new drug development. Chronic inflammation derived from deregulated cytokines with myelosupressive potential, ( IL6, TNF-ɑ and INF-λ) is an important factor in LR-MDS. Selective-Serotonin-Reuptake-Inhibitors (SSRIs) provide clinical benefit in depressed and rheumatoid arthritis pts, at least in part by stabilizing TNF-ɑ and IL6 levels (Brunoni AR., et al. Ann Rev of Med. 2013). In colon and prostate cell lines SSRIs inhibit proliferation. This data suggests that SSRIs may act in at least two ways that would be beneficial in MDS. Here we investigate clinical benefit of SSRIs in treating a subgroup of MDS patients with refractory anemia (RA-MDS). Methods : One hundred and twenty patients over the age of 18-diagnosed with MDS were identified in the Michael E. DeBakey VA Medical Center cancer registry between January 1, 2000 to December 31 2012. Of these, 55 LR-MDS pts with anemia were identified. Patients were considered to be SSRI+ if they had received at least 6 months of a SSRI (including fluoxetine, sertraline, paroxetine or citalopram) in the 12 months preceding or following the diagnosis of MDS. Overall Survival for the SSRI+ and SSRI- groups were estimated by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to assess the impact of multiple independent variables on clinical outcome Results: Among the 55 patients studied, 8 and 47 belonged to SSRI+ and SSRI- groups, respectively. Mean age in the SSRI+ group was 69.5 years (median 72, range 55 to 82) and in the SSRI- group was 74.2 years (median 75, rangе 53 to 88); P=0.252. WHO 2008 classification for SSRI+ group was RUCD 3 [37.5%] and RCMD 5 [61.5%]; For the SSRI- group the classification was RUCD 13 [27.7%]; RCMD 30[63.8%]; RAEB 2[4.3]; MDS MPN unclassified 1[2.1%] and MDS 5q- 1[2.1%]. Median hemoglobin (Hb) level in the SSRI+ group was 10.5 g/dL (8-12 g/dL) and in the SSRI- group was 8.9 g/dL (range, 6-13), P=0.027. Given the central interest of anemia impact on Overall Survival (OS), adjustment for heterogeneity in Hb levels among SSRI+ and SSRI- groups was performed using subgroup survival analysis in pts with equivalent Hb levels (pts with Hb Conclusions: Improved survival of LR-MDS anemic pts is central to treatment paradigms of MDS. Our study suggests survival improvement in LR- MDS pts treated with SSRIs. Potential clinical beneficial effect of SSRIs could be restricted to LR-MDS pts presenting with anemia. Prospective studies aimed at investigating molecular mechanisms of action, potential overall response rate as single agents or in combination with other MDS directed therapy are needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.