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Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized trial of adults, age ≥50 years at high risk for cardiovascular disease with a seated systolic blood pressure (BP) of 130 to 180 mm Hg and a standing systolic BP ≥110 mm Hg. Participants were randomized to a systolic BP treatment goal of either <120 or <140 mm Hg. OH was defined as a drop in systolic BP ≥20 or diastolic BP ≥10 mm Hg 1 minute after standing from a seated position. We used Cox models to examine the association of OH with cardiovascular disease or adverse study events by randomized BP goal. During the follow-up period (median 3years), there were 1170 (5.7%) instances of OH among those assigned a standard BP goal and 1057 (5.0%) among those assigned the intensive BP goal. OH was not associated with higher risk of cardiovascular disease events (primary outcome: hazard ratio 1.06 [95% CI, 0.78–1.44]). Moreover, OH was not associated with syncope, electrolyte abnormalities, injurious falls, or acute renal failure. OH was associated with hypotension-related hospitalizations or emergency department visits (hazard ratio, 1.77 [95% CI, 1.11–2.82]) and bradycardia (hazard ratio, 1.94 [95% CI, 1.19–3.15]), but these associations did not differ by BP treatment goal. OH was not associated with a higher risk of cardiovascular disease events, and BP treatment goal had no effect on OH’s association with hypotension and bradycardia. Symptomless OH during hypertension treatment should not be viewed as a reason to down-titrate therapy even in the setting of a lower BP goal. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01206062.

Background The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. Methods Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm—the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. Results For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. Conclusions The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum.

Abstract Background: NK/T cell non-Hodgkin lymphomas (NK/T NHL) are rare high-grade lymphomas that are diagnostically challenging and carry a poor prognosis. Incidence is notably higher in Asian countries as compared to North America and Europe. South Americans have an incidence similar to Asian countries though less well described. In this study we reviewed the incidence and outcomes of NK/T NHL in the US with a specific focus on patient race/ethnicity. Methods: Surveillance, Epidemiology and End Results (SEER) database was used to examine the standardized incidence rates (SIR) of NK/T cell NHL among adult (≥18 yrs) patients diagnosed between 1992-2013. Mutually exclusive race/ethnicity categories were: African-Americans (AA), Asians/Pacific Islanders (API), Hispanic whites (HW) and Non-Hispanic whites (NHW). Cases that received a diagnosis at death certificate/autopsy, no follow-up records, or lacking age at diagnosis, sex, or race/ethnicity documentation were excluded. Age adjusted incidence rates (AAIR) were calculated by race. Cox proportional hazards models, adjusted for confounding variables, were used to evaluate association between patient demographics and overall survival (OS). Results: A total of 706 cases met inclusion criteria. Of these, 64% were males and 36% females. AAIR was higher in males irrespective of race/ethnicity. Among different race/ethnic subgroups, API and HW had a higher AAIR than NHW and AA (0.2, 0.18, 0.05 and 0.04, respectively) (Figure 1). Median OS for males and females was similar (1.8 yr and 2 yr, respectively; p=0.76) There was a statistically significant difference in median OS by age for all patients with 4.3 yr for age 18-44 as compared with 0.8 yr for age >75 yr (p<0.001). Median OS by was different for HW (1.3 yr), API (1.8 yr), AA (2.3 yr) and HW (2.5 yr) but did not reach statistical significance (p=0.45). Median OS by stage varied as 7.3 yr for stage IE to 0.9 yr for all other stages combined (p<0.001) Cases with disease location as nasal cavity or sinus had a median OS of 3.5 yr as against 1.1 yr for those with all other sites (p<0.001) (Table 1). Conclusions: Significant disparities exist in the US for NK/T NHL incidence by race and gender, with highest AAIR among the racial minorities of API and HW, which are fastest and second fastest growing minority groups in the US respectively. Increasing age, advanced disease stage and site outside of the nasal cavity or sinus are independent predictors of poor prognosis. Some differences do exist in survival by race. These factors need to be considered for better resource allocation and utilization for this rare, often incurable and aggressive disease. Figure 1 Figure 1. Disclosures Ailawadhi: Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy. Kelly:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau.

Abstract Background: DLBCL is the most common adult NHL and despite significant advancements, outcomes in ethnic minorities remain suboptimal. Factors responsible for these disparities in ethnic minorities, especially variability in clinical and pathological features with evaluation of patient-level data have not been studied. Methods: A multi-institutional database of DLBCL patients seen at Mayo Clinic in Florida, University of Miami and University of Southern California between 1996-2016 was developed. Patient demographics, clinical disease characteristics and details of DLBCL immunophenotype [CD10, MUM1, BCL6 (Han's classification), Ki 67, MYC, BCL2) were reviewed. Comparisons between Hispanic and Non-Hispanic patients were made by Chi-square, Fischer's exact and Signed rank tests, where applicable. Patients with missing data on a certain feature were not included in the statistical analysis of that specific characteristic. Results: A total of 966 DLBCL patients with 69 Hispanics and 752 non-Hispanics were identified. These included 52% males (N=36) and 48% females (N=33) in Hispanics versus 58% males (N=436) and 42% females (N=316) in Non-Hispanics (p=0.35). Median age at diagnosis was significantly lower at 61 years (range 27-89) in Hispanics versus 66 in non-Hispanics (p=0.014). Extranodal disease was seen significantly more commonly in Hispanics (74%) than in non-Hispanics (60%) (p=0.037). There was no significant difference in disease stage at presentation between the two cohorts (p=0.189) although the proportion of patients with stage III and IV disease was higher among Hispanics (80.4%) as compared to non-Hispanics (68.5%). Similarly there was no significant difference in presence of primary CNS DLBCL at diagnosis between the two groups (p=0.74). GCB phenotype per the Hans' classification was seen in 59% (N=29) in both, Hispanics and Non-Hispanics (N=241) (p=0.99). Similarly, the median ki67 index of 80% was seen in both cohorts (p=0.48). MYC was positive in 59% in Hispanics versus only 37.5% in non-Hispanics (p=0.024). BCL2 expression by itself and also combined BCL2 and MYC double expression were not significantly different between the two groups (p=0.58 and p=0.11, respectively). Median overall survival (OS) was 22.5 months in Hispanics compared 54.9 months in Non-Hispanics (p<0.0001) (Figure 1). Conclusion: Survival outcome disparities in racial and ethnic minorities have been previously reported from population-based analyses. Lack of patient-level clinical data makes these analyses hypothesis generating, but not conclusive. We confirmed some prior findings including younger age at diagnosis for Hispanics with DLBCL. We also reported greater incidence of extranodal as well as stage III or IV disease at the time of presentation among Hispanics which may contribute to poor outcomes in this population. From DLBCL pathology standpoint, we found increased expression of MYC among Hispanics but no other significant immunohistochemical differences including double expression or non-GCB phenotype. The inferior OS despite uniform treatment practices at large Cancer Centers suggest multifactorial influences on patient outcomes which may at least in part include some of the differences we report here. Disclosures Ailawadhi: Pharmacyclics: Research Funding; Janssen: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy.

Abstract Background: Recent reports from the thalassemia literature suggest that serum ferritin may be a poor and possibly misleading measure of total iron store in heavily iron overloaded patients. Moreover, the relationship between plasma ferritin and body iron stores is distorted by ascorbate deficiency, fever, infection, inflammation, and hepatic dysfunction, all of which occur in patients with sickle cell disease (SCD). On the other hand, following the results of multiple studies that demonstrated a high correlation of hepatic iron overload determination by magnetic resonance imaging to the values found in specimens from liver biopsy, R2* liver MRI has emerged as the best noninvasive yet highly sensitive and specific method for measuring the level of iron in the liver. The goal of this study was to determine the correlation of liver iron by liver R2* MRI with serum ferritin and by extrapolation assess whether serum ferritin remains to be a useful clinical marker of iron overload in patients with SCD. We also sought to determine the correlation of liver iron concentration with abnormalities in the liver function tests. Methods: We conducted a retrospective analysis of 31 patients with sickle cell disease and transfusional iron overload who are being followed at the Augusta University Comprehensive Sickle Cell Center. Serum ferritin, hepatic R2* MRI liver iron concentration, hepcidin level, and liver function tests (AST, ALT and total bilirubin) were assessed for correlation. We used the Pearson correlation coefficient to determine the relationship between the various variables with hepatic R2* MRI. Results: Serum ferritin levels showed a statistically significant positive correlation with R2* hepatic MRI (r = 0.479 with p = 0.0085) in the patients with SCD and transfusional iron overload . We also saw a positive correlation, although not statistically significant, between hepcidin level and liver iron concentration by liver MRI(r=0.493 with P= 0.399). This may be due to the small sample size of the patients who had hepcidin levels available. On the other hand, no correlation was detected between abnormalities in liver function tests and liver iron concentration. The correlation between liver iron concentration(LIC) and AST was 0.045 with p = 0.816 and the correlation between LIC and ALT was 0.233 with p = 0.224. Conclusion: While R2* MRI is the the most accurate method to diagnose and monitor response to therapy in SCD patients with transfusional iron overload, we have found a statistically significant positive correlation with serum ferritin values. Thus, where R2* liver MRI is unavailable, serum ferritin remains a clinically useful tool that can be used in the diagnosis and monitoring of iron overload in sickle cell patients, despite its limitations. As previously reported, we did not find any correlation between LIC and liver function abnormalities in this population (Harmatz et al, 2000) These findings suggest that patients with SCD may have a different response to iron overload in comparison to patients with thalassemia or hereditary hemochromatosis. Disclosures Kutlar: Bluebird Bio: Other: DSMB Member; Sancilio: Other: DSMB Chair; Novartis: Consultancy, Honoraria, Other: Personal fees, Research Funding.

Abstract Introduction: Slow rate of myeloid recovery at the end of induction chemotherapy reflected by a low absolute neutrophil count (ANC) is highly predictive of relapse in children with ALL (Laughton et al, 2005). Whether rate of myeloid recovery is predictive of outcome post-hematopoietic stem cell transplantation (HSCT) in children and young adults has not been studied. Objective: To explore the association between early ANC recovery and survival in children and young adults undergoing allogeneic and autologous HSCT for leukemia or lymphoma. Methods: Retrospective chart review was performed for all consecutive patients (age 6 months to 21 years) undergoing first HSCT for hematologic malignancies and lymphomas at Mayo Clinic, Division of Pediatric Hematology/Oncology from 1995 to 2004. Day 15 and day 28 ANC were calculated for all patients. The primary end point was 1-year relapse free (RFS) and overall survival (OS). To explore the association between ANC and primary outcome, patients were stratified in 2 groups: ≥ or < than median ANC and Kaplan Meier survival curves were generated for both the groups and compared with the log-rank test. Matched related donor (MRD), matched unrelated donor (MUD) and haploidentical (as one group) and autologous transplantations were analyzed separately. Results: There were a total of 50 patients. 28 received MRD, 2 MUD, 10 haploidentical and 10 autologous. The underlying malignancies were (AML n =25, Biphenotypic Leukemia n=1, ALL n =7, NHL n=3, HD n=7, JMML n=5, CML n=2, CLL n=1). No patient was lost to follow up during that time and data was available for all except (day 28 ANC) for one patient. The 1-year RFS and OS rate was the same; 81% for the MRD, 50% for MUD and haploidentical and 70% for autologous transplant populations, respectively. In patients receiving MRD transplants, higher ANC at either day 15 or day 28 post transplantation was associated with better, albeit statistically non-significant, RFS/OS rates at 1 year (86% for ≥ median (0.68) vs. 76% for < median p=0.44 and 92% for ≥ median (2.2) vs. 72% for < median p= 0.18 respectively). Opposite results were observed for MUD and Haploidentical transplantation group (33% for ANC ≥ median (0.47) at day 15 vs. 66% for < median p=0.28, 43% for ANC ≥ median (1.9) at day 28 vs. 60% for < median p=0.48). For autologous transplant group, higher ANC at day 15 was associated with better, albeit statistically non-significant, RFS/OS rates at 1 year (80% for ANC ≥ median (0.42) vs. 60% for < median p=0.60) while opposite results were observed on day 28 (60% for ANC ≥ median (0.46) vs. 75% for < median p=0.54). Conclusions: Our data generated conflicting findings of the association between ANC and RFS/OS in different patient populations undergoing HSCT. However, our results are limited by the small sample size. Further collaborative studies are needed to explore this association.

Abstract Introduction: Early lymphocyte recovery predicts outcome in adults undergoing high dose chemotherapy followed by autologous stem cell transplantation for a variety of malignancies (Porrata et al; 2001, 2002, 2005). Whether rate of lymphoid recovery is predictive of outcome post-hematopoietic stem cell transplantation (HSCT) in children and young adults has not been studied. Objective: To explore the association between early ALC recovery and survival in children and young adults undergoing allogeneic and autologous (HSCT) for leukemia or lymphoma. Methods: Retrospective chart review was performed for all consecutive patients (age 6 months to 21 years) undergoing first HSCT for hematologic malignancies and lymphomas at Mayo Clinic, Division of Pediatric Hematology/Oncology from 1995 to 2004. Day 15 and day 28 ALC were calculated for all patients. The primary end point was 1-year relapse free (RFS) and overall survival (OS). To explore the association between ALC and primary outcome, patients were stratified in 2 groups: ≥ or < than median ALC and Kaplan Meier survival curves were generated for both the groups and compared with the log-rank test. Matched related donor (MRD), matched unrelated donor (MUD) and haploidentical (as one group) and autologous transplantations were analyzed separately. Results: There were a total of 50 patients. 28 received MRD, 2 MUD, 10 haploidentical and 10 autologous transplant. The underlying malignancies were AML n =25, Biphenotypic Leukemia n=1, ALL n =7, NHL n=3, HD n=7, JMML n=5, CML n=2, CLL n=1). No patient was lost to follow up during that time and data was available for all except (day 28 ALC) for one patient. The 1-year RFS and OS rate was the same; 81% for the MRD, 50% for MUD and haploidentical and 70% for autologous transplant populations, respectively. In patients receiving MRD transplants, higher ALC at either day 15 or day 28 post transplantation was associated with better, albeit statistically non-significant, RFS/OS rates at 1 year (85% for ≥ median (0.23) vs. 78% for < median p=0.69 and 86% for ≥ median (0.47) vs. 77% for < median p= 0.59 respectively). Opposite results were observed for MUD and Haploidentical transplantation group (33% for ALC ≥ median (0.05) at day 15 vs. 67% for < median p=0.2, 33% for ALC ≥ median (0.35) at day 28 vs. 66% for < median p=0.28) and for autologous transplantations (67% for ALC ≥ median (0.23) at day 15 vs. 75% for < median p=0.68, 40% for ALC ≥ median (0.48) at day 28 vs. 100% for < median p=0.07). Conclusions: Our data generated conflicting findings of the association between ALC and RFS/OS in different patient populations undergoing HSCT. However, our results are limited by the small sample size. Further collaborative studies are needed to explore this association.