Abstract MP57: A South Asian Mediterranean-style Diet Pattern Is Associated With Favorable Measures Of Adiposity And A Lower Risk Of Incident Diabetes: Findings From The Masala Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Sharan K Rai ◽  
Alka M Kanaya ◽  
Namratha Kandula ◽  
Qi Sun ◽  
Shilpa N Bhupathiraju
Keyword(s):  
South Asian ◽  
South Asians ◽  
Subclinical Atherosclerosis ◽  
Cultural Beliefs ◽  
P Value ◽  
Inverse Association ◽  
Processed Meats ◽  
Lower Likelihood ◽  
Diet Pattern

Introduction: South Asians are at a disproportionately high risk for cardiometabolic disease. The Mediterranean diet is associated with reduced risks of type 2 diabetes (T2D) and cardiovascular disease in certain populations, although data among South Asians are lacking. Therefore, we evaluated the association between a novel South Asian Mediterranean style (SAM) diet pattern and a broad panel of cardiometabolic markers from the MASALA study, an ongoing prospective cohort of South Asians in the US. Methods: We included 891 participants who completed the baseline visit (2010-13) with reliable responses to a validated ethnic-specific food frequency questionnaire (mean age 55 y; 47% female). We created the SAM score by grouping foods including those specific to this population’s cuisine into 9 pre-defined categories (vegetables, fruits, legumes, nuts, whole grains, red/processed meats, fish, alcohol, and monounsaturated to saturated fat ratio). Participants above the median intake received 1 point per category; red/processed meats were reverse scored and those with alcohol intake 5-25 g/d received 1 point. We summed these for a score from 0-9, with higher scores reflecting greater adherence to a Mediterranean style diet. Participants underwent a clinical exam, carotid ultrasound, cardiac and abdominal CT, and fasting blood tests. We used multivariable linear and logistic regression to examine cross-sectional associations between the SAM score and cardiometabolic risk, adjusting for age, sex, calories, physical activity, smoking status, medical history, income, education level, and cultural beliefs. We additionally adjusted for body mass index (BMI) in the full model. Finally, we examined the association between the SAM score and incident T2D at follow-up (~5 y later). Results: Participants with higher SAM scores tended to be older, more likely to have a bachelor’s degree, less likely to report experiences of discrimination, and less likely to be smokers. At baseline, the SAM score was inversely associated with pericardial fat volume (-1.22 ± 0.55 cm 3 per 1-unit increase in SAM score; p value=0.03) in the fully adjusted model. We observed an inverse association between the SAM score and visceral fat, but it was attenuated after additionally adjusting for BMI. There were no associations with subclinical atherosclerosis, glycemia measures, lipids, inflammatory markers, or uric acid. The SAM score was associated with a lower likelihood of obesity (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.79 to 0.98) and fatty liver (OR 0.82, 95% CI 0.68 to 0.98), but not with hypertension. Finally, the SAM score was associated with lower odds of incident T2D (OR 0.75, 95% CI 0.59 to 0.95) at follow-up. Conclusion: A greater intake of a Mediterranean style diet that incorporates traditional South Asian foods was associated with favorable measures of adiposity and a lower likelihood of incident T2D.

scholarly journals Outcomes of COVID-19: disparities by ethnicity

2020 ◽  
Author(s):  
Hamad Ali ◽  
Abdullah Alshukry ◽  
Sulaiman K Marafie ◽  
Monera AlRukhayes ◽  
Yaseen Ali ◽  
...  
Keyword(s):  
South Asian ◽  
Regression Models ◽  
South Asians ◽  
P Value ◽  
Multivariate Logistic Regression ◽  
Death Rates ◽  
Logistic Regression Models ◽  
Asian Patients ◽  
Worse Prognosis

AbstractObjectivesTo investigate the role of ethnicity in COVID-19 outcome disparities in a cohort in Kuwait.MethodsThis is a retrospective analysis of 405 individuals infected with SARS-CoV-2 in Kuwait. Outcomes such as symptoms severity and mortality were considered. Multivariate logistic regression models were used to report the odds ratios (OR) for ICU admission and dying from COVID-19.ResultsThe cohort included 290 Arabs and 115 South Asians. South Asians recorded significantly higher COVID-19 death rates compared to Arabs (33% vs. 7.6%, P value<0.001). When compared to Arabs, South Asians also had higher odds of being admitted to the ICU (OR = 6.28, 95% CI: 3.34 – 11.80, p < 0.001). South Asian patients showed 7.62 (95% CI: 3.62 – 16.02, p < 0.001) times the odds of dying from COVID-19.ConclusionCOVID-19 patients with South Asians ethnicity are more likely to have worse prognosis and outcome when compared to patients with Arab ethnicity. This suggest a possible role for ethnicity in COVID-19 outcome disparities and this role is likely to be multifactorial.

scholarly journals Lipid profile outcome gaps of Arabs and South Asians receiving chronic Statin therapy

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 2194-2200
Author(s):  
Zahra Alagheband ◽  
Seeba Zachariah ◽  
Dixon Thomas ◽  
Dave L Dixon
Keyword(s):  
Lipid Profile ◽  
Statin Therapy ◽  
South Asian ◽  
South Asians ◽  
Lipid Profiles ◽  
Lipid Lowering ◽  
P Value ◽  
Lipid Lowering Therapy ◽  
Therapy Outcomes ◽  
Lowering Therapy

Ethnicity is a variable in statin response, but the influence of it in Arabs and South Asians is not known. There is a possibility of under-treatment in the long-term management of dyslipidemia in the Arab population, ignoring post-initiation medication nonadherence and lifestyle. There could be potential genetic reasons also for the need for higher lipid-lowering therapy in Arabs. This study is to identify lipid profile outcome gaps of Arabs and South Asians who were receiving chronic statin therapy. A hypothesis generating retrospective cohort study was conducted to compare lipid profiles among patients treated with a statin for more than three months. The study compared two lipid profiles of Arab and South Asian patients on chronic management of dyslipidemia. T-test and Z-test were performed to compare the lipid profiles. The study participants included 42 Arabs and 28 South Asians. Arabs had a higher body mass index (P-value 0.05), and more of them were smokers compared to South Asians (P-value 0.04). Total cholesterol (P-value 0.03, 95%CI 1.08 to -21.29) and LDL cholesterol (P-value 0.03, 95% CI 0.51 to -17.51) reductions in 3 – 6 months were significant in South Asians, but not in Arabs. The lipid profiles in Arabs receiving chronic statin therapy might be poor compared to South Asians. Both populations need improvements in lipid-lowering therapy outcomes. This hypothesis should be studied further to prove inherent differences and poor therapy outcomes among Arab and South Asian population that might result in modifications in current healthcare management policies.

Abstract P277: Exercise is Associated With Social Network Characteristics Among South Asian Immigrants

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Mitali Thanawala ◽  
Juned Siddique ◽  
Andrew Cooper ◽  
John A Schneider ◽  
Swapna Dave ◽  
...  
Keyword(s):  
Physical Activity ◽  
Social Networks ◽  
Social Network ◽  
South Asian ◽  
South Asians ◽  
Asian Immigrants ◽  
Network Member ◽  
P Value ◽  
South Asian Immigrants ◽  
Network Characteristics

Objective: Low physical activity increases cardiovascular disease (CVD) risk. Social context, operationalized through social networks, has been shown to drive health behaviors. This study examined the association between personal social networks and moderate-to-vigorous leisure-time physical activity (LTPA) among South Asian (Indian, Pakistani, Bangladeshi, Sri Lankan, Nepalese) immigrants, a group with high CVD rates. Methods: This study used cross-sectional data from an ancillary study of social networks (2014-2017) in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study cohort. Participants, free from CVD at baseline and living in the San Francisco Bay-area, CA and Chicago, IL, were administered a detailed social networks questionnaire and physical activity questionnaire adapted from the Cross-Cultural Activity Participation Study. Participants reported on the exercise behaviors of each social network member and if they exercised with the network member. Network members who exercised with a participant were categorized as exercise partners. Moderate-vigorous LTPA was calculated as Metabolic Equivalent of Task (MET) minutes per week. Sex-stratified, linear regression models were used to examine associations between social network characteristics and MET-min/week of LTPA, independent of age, marital status, and network size. The effect of having an exercise partner in the network, above simply having network members who exercised, was tested using a partial F-test to compare nested models. Results: Among the 700 participants, this analysis only included the 89% who reported any LTPA (n=623, 43% female). These individuals reported a median of 1335 MET-min/week of LTPA (IQR=735-2212 MET-min/week) and had an average of 4 network members (SD +/- 1). The proportion of network members who exercised was 0.89, and the proportion of exercise partners was 0.28. Exercise partners were most commonly spouses (56%) and friends (20%). Among South Asian men who exercised, having a social network member who exercised instead of having a non-exercising network member, significantly increased LTPA by 310 MET-min/wk (95% CI=152-470). For men, having a social network member who was an exercise partner instead of a non-exercising network member, was associated with an additional 520 MET-min/wk of LTPA (95% CI= 344-696). The effect on LTPA of having an exercise partner in the network was significantly greater than the effect of simply having a network member who exercised (p-value < 0.001). Results were similar for women, but not statistically significant (p-value=0.05). Conclusions: Among South Asian immigrants, having an exercise partner in one’s personal social network was associated with significantly more LTPA. Social network support, in the form of an exercise partner, may be an effective component of interventions to promote LTPA in South Asians.

Abstract 16217: Culturally-tailored Team-based Preventive Cardiology Program Improves Cardiovascular Risk for South Asian Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Keon Pearson ◽  
Vijaya Parameswaran ◽  
Destini Gibbs-Curtis ◽  
Austin Johnson ◽  
Kiranbir Josan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Total Cholesterol ◽  
South Asian ◽  
South Asians ◽  
Clinical Intervention ◽  
High Sensitivity ◽  
Initial Assessment ◽  
Preventive Cardiology ◽  
Culturally Tailored

Introduction: South Asians (SA) have a two times greater prevalence of CAD and metabolic syndrome (MetS) than matched Europeans. Diet and physical activity may be best addressed through culturally-tailored interventions. The Stanford South Asian Translational Heart Initiative (SSATHI) was designed to help SA better understand and improve their risk factors. We tested the hypothesis that a team-based and culturally-tailored clinical intervention for SA would result in a reduction in MetS risk factors. Methods: Patients underwent an initial assessment consisting of fasting lipid profile, advanced lipid studies (lipid fractionation, lp (a), apoA1, apoB), inflammatory markers (high sensitivity CRP, homocysteine), and A1c. All non-diabetics underwent two-hour OGTT. Following initial assessment by a cardiologist, a registered dietician developed a personalized nutrition plan based on SA cuisine. Results: A total of 395 patients were seen between July, 2011 and July, 2019. Of these, 198 (50%) completed at least two cardiologist visits with baseline and follow up labs. Patients had an average age of 45.5 years and 86% were male. At baseline, SSATHI patients had a mean BMI of 26.4 (IQR = 23.9-28.8), 52% of patients had total cholesterol greater than 190 mg/dl, 21% had systolic BP > 140 mmHg, and 13% had diastolic BP > 90 mmHg. During an average follow-up of 11.8 ± 9.2 months, diastolic BP declined from 80.9 ± 9.32 to 78.9 ± 7.6 mmHg (p = 0.028), total cholesterol decreased from 190.4 ± 46.4 to 153.4 ± 63.7 mg/dl (p < 0.001), total triglycerides declined from 137.1 ± 87.1 to 100.2 ± 67.5 mg/dl (p < 0.001), and LDL declined from 120.4 ± 40.0 to 92.3 ± 46.4 mg/dl (p <0.001). HDL declined from 49.0 ± 15.4 to 44.5 ± 19.8 mg/dl (p = 0.022). ASCVD and A1c were not significantly different. Conclusion: A team-based and culturally-informed program targeted to South Asian populations may help improve cardiometabolic risk factors but may be limited by program attrition and generalizability.

Abstract P386: Adult Height and Coronary Artery Calcium in the NHLBI Family Heart Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Michael D Miedema ◽  
Andrew Petrone ◽  
James Pankow ◽  
Steven C Hunt ◽  
Aldi T Kraja ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Artery Calcium ◽  
Adult Height ◽  
Subclinical Atherosclerosis ◽  
P Value ◽  
Inverse Association ◽  
Odds Ratios ◽  
Family Heart Study ◽  
Heart Study ◽  
The Relationship

Introduction: Adult height is inversely associated with the risk of developing hypertension, hyperlipidemia, and diabetes. Height has also shown an inverse association with coronary heart disease and cardiovascular mortality, but the relationship between height and subclinical atherosclerosis is unclear. Coronary artery calcium (CAC) is a marker of atherosclerosis and a strong predictor of cardiovascular events. The relationship between height and CAC has not been well studied. Objective: To test the hypothesis that adult height is inversely associated with CAC. Methods: We studied 3,360 individuals from the National Heart, Lung, and Blood Institute Family Heart Study. Adult height was self-reported and CAC was measured by EBCT. We used generalized estimating equations to estimate adjusted prevalence odds ratios across quintiles of height. Results: Mean age of the sample was 54.9 years (SD +/- 12.9) and 57% were women. Baseline characteristics of the participants in sex-specific quintiles are shown in Table 1. After adjusting for age, the prevalence odds ratios for CAC decreased from the lowest quintile to the highest quintile (p-value for trend 0.02). After further adjustment for race, waist circumference, smoking, and field center, height remained inversely associated with CAC (adjusted odds ratios 1.0 [reference], 1.52 [1.13-2.05], 0.98 [0.75-1.28], 0.90 [0.68-1.20], 0.78 [0.58-1.03], p-value for trend <0.01). Additional adjustment for alcohol consumption, exercise, and total cholesterol did not materially change the strength of the association between height and CAC. No interaction was seen for gender or race. Conclusion: Adult height is inversely associated with the presence of CAC in middle-aged men and women.

Abstract 163: Association of Diabetes With Coronary Artery Calcium in South Asians, African Americans, Caucasians, Chinese, and Hispanics: The Multi-Ethnic Study of Atherosclerosis (MESA) and the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ned Premyodhin ◽  
Wenjun Fan ◽  
Millie Arora ◽  
Masood Younus ◽  
Matthew J Budoff ◽  
...  
Keyword(s):  
Coronary Artery ◽  
African Americans ◽  
Ethnic Groups ◽  
Coronary Artery Calcium ◽  
South Asians ◽  
Subclinical Atherosclerosis ◽  
Study Cohort ◽  
Atherosclerotic Cardiovascular Disease ◽  
Normal Glucose

Introduction: South Asians (SA) have increased atherosclerotic cardiovascular disease (ASCVD) risk and SA ethnicity is considered a “risk-enhancing factor” in the latest prevention guidelines. Diabetes mellitus (DM) is common in SA, but it is not known how pre-DM or DM may contribute to subclinical atherosclerosis in SA compared to other ethnic groups. We examined the association of pre-DM and DM to coronary artery calcium (CAC) in SA compared to 4 other ethnic groups. Methods: We studied data from SA, African Americans (AA), non-Hispanic whites (NHW), Chinese (CH), and Hispanics (HS) aged 45-84 without known ASCVD. SA were taken exclusively from MASALA and other groups from MESA. The prevalence of CAC 0, 1-99, 100-399, and 400+ were examined among those who were normoglycemic, pre-DM and DM. Multiple logistic regression adjusted for age, sex, smoking, cholesterol, and blood pressure identified the associations of pre-DM and DM (compared to normal glucose) on the odds of any CAC > 0 and significant CAC ≥ 100 by ethnicity. Results: Of the 7587 included individuals, mean age was 62±10 years, with 48% men, 10% SA, 25% AA, 34% NHW, 11% CH and 20% HS. The prevalence of pre-DM and DM varied significantly (p < 0.01) across ethnic groups: SA (25% and 21%), AA (15% and 18%), NHW (11% and 6%), CH (17% and 13%) and HS (15% and 17%). The prevalence of any CAC and CAC ≥ 100 in those with DM were highest in NHW (80% and 48%) and SA (72% and 41%). Pre-DM was only associated with CAC ≥ 100 in NHW (OR = 1.5, p < 0.01). Compared to other groups, SA with DM (compared to those normoglycemic) had the highest odds ratios (ORs) for CAC > 0 (OR = 3.35, p < 0.01) and CAC ≥ 100 (OR = 3.10, p < 0.01) (p = 0.01 and 0.07 for ethnicity interactions, respectively) (Table). Conclusions: Diabetes was associated with higher odds of any or significant CAC among SA compared to other ethnic groups. Ongoing longitudinal follow-up of the MASALA study cohort might help explain if DM contributes to the often premature ASCVD outcomes in SA.

scholarly journals Anthropometric indices and the risk of incident sudden cardiac death among adults with and without diabetes: over 15 years of follow-up in The Tehran Lipid and Glucose Study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Seyyed Saeed Moazzeni ◽  
Seyed Saeed Tamehri Zadeh ◽  
Samaneh Asgari ◽  
Fereidoun Azizi ◽  
Farzad Hadaegh
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Categorical Variables ◽  
P Value ◽  
Inverse Association ◽  
Multivariable Model ◽  
Anthropometric Indices ◽  
Group A ◽  
Fourth Quartile

Abstract Background We investigated the association of anthropometric indices including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and hip circumference (HC) with the risk of incident sudden cardiac death (SCD) among Iranian population with and without type 2 diabetes mellitus (T2DM). Methods The study population included 9,089 subjects without and 1,185 subjects with T2DM, aged ≥ 20 years. Participants were recruited in 1999–2001 or 2001–2005, and followed for incident SCD annually, up to 20 March 2018. Multivariate Cox proportional hazard models, adjusted for traditional risk factors of cardiovascular disease, were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of anthropometric indices (as continuous and categorical variables). Results During a follow-up of over 15 years, 144 (1.58%) and 86 (7.26%) incident SCD occurred in non-T2DM and T2DM groups, respectively. Among non-T2DM group, a 1 standard deviation (SD) increase in WHtR was associated with higher risk of incident SCD by a HR of 1.23 (95% CI: 1.00–1.50) in the multivariable model. From the first quartile to the fourth quartile of WHtR, the trend of SCD risk was significant in age- and sex-adjusted analysis (P-value for trend: 0.041). Other indices did not show significant associations with SCD. Among T2DM group, a 1 SD increase in WHR had a HR of 1.36 (1.05–1.76) in the multivariable model. Considering WHR as categorical variables, the trend of SCD risk across quartiles of WHR was significant. Furthermore, a 1 SD increase in HC led to reduced risk of incident SCD with a HR of 0.75 (0.58–0.97) in multivariable analysis; this lower risk remained significant even after adjustment for WC. Compared to the first quartile, the fourth quartile of HC also showed a HR of 0.50 (0.25–0.99) (P-value for trend = 0.018). BMI, WC, and WHtR did not have significant associations with incident SCD. Conclusion In our long-term population-based study, we demonstrated central but not general obesity (as assessed by WHR in participants with T2DM, and WHtR in participants without T2DM) as a herald of incident SCD. Moreover, HC can have an inverse association with SCD among participants with T2DM.

Abstract P126: Comparing Cardiovascular Risk Factor Progression Between South Asian Men and Women With Diabetes: A Longitudinal Analysis From the Masala Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Manasi Deshpandey ◽  
Chiung-Yu Huang ◽  
Namratha Kandula ◽  
Alka M Kanaya
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
South Asian ◽  
Ldl Cholesterol ◽  
South Asians ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Men And Women ◽  
Asian Men

Introduction: South Asians have a high incidence of type 2 diabetes(DM) and cardiovascular disease (CVD). Women with DM may have greater CVD risk compared to men with DM and women without DM. No study has determined whether the incidence or progression of coronary artery calcium (CAC) score, a measure of atherosclerosis burden, differs between South Asian men and women with DM. Hypothesis: We hypothesize that CAC progression is greater in women with DM as compared to men with DM and women without DM. Methods: We used the data from the MASALA study, a community-based prospective cohort of South Asians from 2 clinical sites without CVD at baseline. We conducted a longitudinal analysis of diabetic participants who were reassessed after 5 years and compared with those without diabetes. We classified incident CAC as any CAC at exam 2 in a participant who had no CAC at baseline. To examine the progression of CVD risk factors over time, we compared change in CAC score, waist circumference, systolic and diastolic blood pressure, HbA1c and lipid levels amongst the diabetic and non-diabetic population by sex. We conducted multivariable linear regression models stratified by diabetes status to determine whether sex was independently associated with change in CAC score and other CVD risk factors. Results: Of 749 participants who were seen in follow-up, 176 (23%) had diabetes at baseline, 65% were men, and mean age was 58 years. Approximately 64% women with DM vs. 28% men with DM had CAC=0, and men had higher median CAC score (49 (IQR 0-247) vs. 0 (IQR 0-46, p<0.001). After mean follow-up of 4.8±0.8 years, incident CAC did not differ between men and women with diabetes (p=0.85). Progression of CAC was greater in men with DM (94, IQR 13-290) compared to women with DM (0, IQR 0-30) (p <0.001). Baseline statin and aspirin use was lower in women with DM (statins: 37% in women vs. 56% in men, p<0.001; aspirin 16% in women vs. 43% in men, p<0.001). In multivariable models, the fold-change in CAC in women (0.22, 95% CI 0.10 - 0.47) was lower than in men (4.54, 95% CI 2.08 - 9.89) and comparable to women without DM (0.30 95%CI 0.21 -0.43), after adjusting for age, baseline CAC, systolic and diastolic blood pressure, total and LDL cholesterol, duration of diabetes, smoking and any medication use (statin, diabetes, or hypertension med). Sex was not associated with change in any CVD risk factor among those with diabetes; but women without DM had greater change in total and LDL cholesterol and waist circumference than men without DM. Conclusion: In this South Asian population, change in CAC score was lower in women with DM than in men with DM, and was comparable to women without DM. These results suggest among South Asians with DM, overall CVD risk may be greater in men than in women.Continued follow-up of the MASALA cohort will determine whether there are sex differences in CVD outcomes.

Predictors and GVL Effects of UCB Chimerism after Haplo-Cord Transplant

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4385-4385
Author(s):  
Nebu Koshy ◽  
Sebastian A. Mayer ◽  
Adrienne Phillips ◽  
Rosanna Ferrante ◽  
Ronit Slotky ◽  
...  
Keyword(s):  
Prospective Study ◽  
Cord Blood ◽  
Relapse Rate ◽  
P Value ◽  
Inverse Association ◽  
Hla Matching ◽  
Cell Dose ◽  
Cd34 Cells

Abstract Haplo cord transplant combines an umbilical cord blood unit (CBU) graft with a CD34 selected adult haplo-identical graft for the purpose of establishing long term CBU chimerism, which occurs in most but not all cases. Previously we showed that excessive haplo CD34 doses impair CBU engraftment (Liu et al, Blood 2011). Since then we have utilized a fixed haplo CD34 dose of 5x106 CD34 cells/kg. We also conducted a prospective study of CBU threshold dose de-escalation and established a minimum CBU dose of 1.2 x106 TNC/kg as the threshold for further study (van Besien ASH 2014, 1093). Here- using the patients from our prospective study- we sought to identify additional predictors of CBU engraftment as measured by percentage of CBU chimerism in CD33 and CD3 lineages in patients engrafted and in remission by day 56. We focused on d56 chimerism because durable patterns of chimerism are established by then. 83 pts were enrolled, but 23 were excluded from analysis because of early death (6) relapse before day 60 (8), failure of both grafts with residual MDS (4), lost to follow up (1) and no chimerism measurements (3). 61 pts were analyzed with median age 62 (18-72 years), 41 AML/MDS, 12 NHL, 5 ALL and 4 others. 24 had ASBMT high risk, 13 intermediate and 23 low risk disease. Conditioning was Flu Mel ATG (n=46), Flu Mel TBI 400 ATG (n=14) and Flu Mel TBI 600 ATG (n=1). All pts received GVHD prophylaxis with tacrolimus until d 180 and mycophenolate until d 30. The haplo dose was fixed at 5 x 106 CD34 cells/kg. Donors targeted by recipient donor specific antibodies (DSA) were avoided if possible. CBU units were selected based on HLA matching in sequential cohorts of decreasing threshold cell dose. Coh 1(n=12), minimum 2.0 x106 TNC/kg, coh 2 min (n=14) 1.5 x106 TNC/kg, coh 3 (n=25) min 1.0 x106 TNC/kg. After min cell dose was established, further enrollment occurred with a min dose of 1.2 x106 TNC/kg (coh 4 n=10). Median CBU TNC across all cohorts was 2.27 x107/kg (1.0-8.3). CBU were matched (HR HLA) at 3/8 (n=1), 4/8 (n=7), 5/8 (n=18), 6/8 (n=14) 7/8 (n=16) and 8/8 (n=5). DSA against CBU were present in 7. Haplo graft was 4/8 (n=42), 5/8 (n=13), 6/8 (n=3) and 7/8 (n=3). DSA against haplo were present in 6. Median follow up for survivors is 16 mo (5 -34). Cord graft characteristics, matching, enrollment cohort, nor presence of DSA were associated with d56 CBU chimerism. There was a strong inverse association between degree of matching of the haplo donor and d56 CBU (Fig 1). 54 pts with ≤ 5/8 haplo HLA match had 68% d56CD33 UCB chimerism vs 14% for the six pts with 6/8 or 7/8 HLA match (p=0.004). There was also a significant association between use of TBI and cord blood engraftment. 15 pts who received TBI had 79% d56CD33 UCB chimerism vs 50% for the 46 pts without TBI (p=0.05). Decreasing d56UCB chimerism was strongly associated with cumulative relapse risk (Fig 2A). It was not associated with TRM. The associations were even stronger if only considering AML/MDS (Fig 2B). Best discrimination was with 40% CD33 and 80% CD3 (Table 1). Table 1. Relapse rate at one year Day 56 CD3 <80% (22) CD3>80% (39) p value CD33<40% (19) CD33>40% (42) p value All pts n= 61 47% 21% 0.006 52% 19% 0.0008 CD3 <80% (15) CD3>80% (26) p value CD33<40% (13) CD33>40% (28) p value AML/MDS n=41 60% 14% 0.0003 58% 16% 0.00007 Conclusions: The establishment of a durable cord blood graft is heavily influenced by HLA matching of the haplo-graft. 6/8 and 7/8 HLA-matched haplo-graft which occur by chance in about 10% of cases, should probably be avoided. More intensive conditioning with the addition of low dose TBI may further favor establishment of the cord blood graft. Cell dose or HLA matching of the cord blood graft has less effect on its long-term establishment. Increasing cord blood chimerism is associated with a much reduced risk of relapse despite- not shown here- very low rates of chronic GVHD). Low levels of cord blood chimerism are associated with very high rates of relapse. These data provide further support for the GVL effects of CBU grafts, particularly in AML/MDS. Figure 1. Relation between Haplo Graft Matching and d56 CD33 CBU chimerism Figure 1. Relation between Haplo Graft Matching and d56 CD33 CBU chimerism Figure 2. Relapse Rate in All patients (A) and AML/MDS (B) based on d56 CD33 chimerism ≥40% vs <40% Figure 2. Relapse Rate in All patients (A) and AML/MDS (B) based on d56 CD33 chimerism ≥40% vs <40% Disclosures van Besien: Miltenyi Biotec: Research Funding.

Fragility index of trials supporting approval of anti-cancer drugs in common solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2055-2055
Author(s):  
Alexandra Desnoyers ◽  
Michelle Nadler ◽  
Ramy Saleh ◽  
Eitan Amir
Keyword(s):  
Solid Tumors ◽  
Randomized Trials ◽  
Statistical Significance ◽  
P Value ◽  
Inverse Association ◽  
Fragility Index ◽  
Real World Data ◽  
Number Of Patients ◽  
Lost To Follow Up

2055 Background: The Fragility Index (FI) quantifies the reliability of positive trials by estimating the number of events which would change statistically significant results to non-significant results. Here, we calculate the FI of trials supporting approval of drugs for common solid tumors. Methods: We searched Drugs@FDA to identify randomized trials (RCT) supporting drug approvals by the US Food and Drug Administration between January 2009 and December 2019 in lung, breast, prostate, gastric and colon cancers. We adapted the FI framework (Walsh et al. J Clin Epidemiol 2014) to allow use of time to event data. First, we reconstructed survival tables from reported data using the Parmar Toolkit (Parmar et al. Stat Med 1998) and then calculated the number of events which would result in a non-significant effect for the primary endpoint of each trial. The FI was then compared quantitatively to the number of patients in each trial who withdrew consent or were lost to follow-up. Multivariable linear regression was used to explore association between RCT characteristics and the FI. Results: We identified 69 RCT with a median of 669 patients (range 123-4804) and 358 primary outcome events (range 56-884). The median FI was 26 (range 1-322). The FI was ≤10 in 21 trials (30%) and ≤20 in 31 trials (45%). Among the 69 RCT, the median number of patients who withdrew consent or were lost to follow up was 27 (range, 6-317). The number of patients who withdrew consent or were lost to follow-up was equal or greater than the FI in 42 trials (61%). There was statistically significant inverse association between FI and trial hazard ratio (p0,001) and a positive association with number of patients who were lost to follow-up or withdrew consent (p0,001). There was no association between trial sample size, year of approval or reported p-value and the FI. Conclusions: Statistical significance of trials supporting drug approval in common solid tumors relies often on a small number of events. In most trials the FI was lower than the number of patients lost to follow up or withdrawing consent. Post-approval randomized trials or real-world data analyses should be performed to ensure that effects observed in registration trials are robust.

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