Racial, Ethnic, and Socioeconomic Factors Result in Disparities in Outcome Among Children with Acute Lymphoblastic Leukemia Not Fully Attenuated By Disease Prognosticators: A Children's Oncology Group (COG) Study

Abstract Introduction: Health disparities are major issue for racial, ethnic, and socioeconomically disadvantaged groups. Though outcomes in childhood acute lymphoblastic leukemia (ALL) have steadily improved, identifying persistent disparities is critical. Prior studies evaluating ALL outcomes by race or ethnicity have noted narrowing disparities or that residual disparities are secondary to differences in leukemia biology or socioeconomic status (SES). We aimed to identify persistent inequities by race/ethnicity and SES in childhood ALL in the largest cohort ever assembled for this purpose. Methods: We identified a cohort of newly-diagnosed patients with ALL, age 0-30.99 years who were enrolled on COG trials between 2004-2019. Race/ethnicity was categorized as non-Hispanic white vs. Hispanic vs. non-Hispanic Black vs. non-Hispanic Asian vs. Non-Hispanic other. SES was proxied by insurance status: United States (US) Medicaid (public health insurance for low-income individuals) vs. US other (predominantly private insurance) vs. non-US patients (mainly jurisdictions with universal health insurance). Event-free and overall survival (EFS, OS) were compared across race/ethnicity and SES. The relative contribution of disease prognosticators (age, sex, white blood cell count, lineage, central nervous system status, cytogenetics, end Induction minimal residual disease) was examined with Cox proportional hazard multivariable models of different combinations of the three constructs of interest (race/ethnicity, SES, disease prognosticators) and examining hazard ratio (HR) attenuation between models. Results: The study cohort included 24,979 children, adolescents, and young adults with ALL. Non-Hispanic White patients were 13,872 (65.6%) of the cohort, followed by 4,354 (20.6%) Hispanic patients and 1,517 (7.2%) non-Hispanic Black patients. Those insured with US Medicaid were 6,944 (27.8%). Five-year EFS (Table 1) was 87.4%±0.3% among non-Hispanic White patients vs. 82.8%±0.6% [HR 1.37, 95 th confidence interval (95CI) 1.26-1.49; p<0.0001] among Hispanic patients and 81.9%±1.2% (HR 1.45, 95CI 1.28-1.56; p<0.0001) among non-Hispanic Black patients. Outcomes for non-Hispanic Asian patients were similar to those of non-Hispanic White patients. US patients on Medicaid had inferior 5-year EFS as compared to other US patients (83.2%±0.5% vs. 86.3%±0.3%, HR 1.21, 95CI 1.12-1.30; p<0.0001) while non-US patients had the best outcomes (5-year EFS 89.0%±0.7%, HR 0.78, 95CI 0.71-0.88; p<0.0001). There was substantial imbalance in traditional disease prognosticators (e.g. T-cell lineage) across both race/ethnicity and SES, and of race/ethnicity by SES. For example, T-lineage ALL accounted for 17.6%, 9.4%, and 6.6% of Non-Hispanic Black, Non-Hispanic White, and Hispanic patients respectively (p<0.0001). Table 2 shows the multivariable models and illustrates different patterns of HR adjustment among specific racial/ethnic and SES groups. Inferior EFS among Hispanic patients was substantially attenuated by the addition of disease prognosticators (HR decreased from 1.37 to 1.17) and further (but not fully) attenuated by the subsequent addition of SES (HR 1.11). In contrast, the increased risk among non-Hispanic Black children was minimally attenuated by both the addition of disease prognosticators and subsequent addition of SES (HR 1.45 to 1.38 to 1.32). Similarly, while the superior EFS of non-US insured patients was substantially attenuated by the addition of race/ethnicity and disease prognosticators (HR 0.79 to 0.94), increased risk among US Medicaid patients was minimally attenuated by the addition of race/ethnicity or disease prognosticators (HR 1.21 to 1.16). OS disparities followed similar patterns but were consistently worse than in EFS, particularly among patients grouped as non-Hispanic other. Conclusions: Substantial disparities in survival outcomes persist by race/ethnicity and SES in the modern era. Our findings suggest that reasons for these disparities vary between specific disadvantaged groups. Additional work is required to identify specific drivers of survival disparities that may be mitigated by targeted interventions. Figure 1 Figure 1. Disclosures Gupta: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Teachey: NeoImmune Tech: Research Funding; Sobi: Consultancy; BEAM Therapeutics: Consultancy, Research Funding; Janssen: Consultancy. Zweidler-McKay: ImmunoGen: Current Employment. Loh: MediSix therapeutics: Membership on an entity's Board of Directors or advisory committees.

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Racial and Ethnic Differences in Presentation and Outcomes for Patients Hospitalized with COVID-19: Findings from the American Heart Association's COVID-19 Cardiovascular Disease Registry

Circulation ◽

10.1161/circulationaha.120.052278 ◽

2020 ◽

Cited By ~ 1

Author(s):

Fatima Rodriguez ◽

Nicole Solomon ◽

James A. de Lemos ◽

Sandeep R. Das ◽

David A. Morrow ◽

...

Keyword(s):

Mechanical Ventilation ◽

Ethnic Differences ◽

American Heart ◽

Disease Registry ◽

Asian Patients ◽

Black Patients ◽

Hispanic Patients ◽

Race Ethnicity ◽

Racial Ethnic ◽

Hispanic White

Background: The COVID-19 pandemic has exposed longstanding racial/ethnic inequities in health risks and outcomes in the U.S.. We sought to identify racial/ethnic differences in presentation and outcomes for patients hospitalized with COVID-19. Methods: The American Heart Association COVID-19 Cardiovascular Disease Registry is a retrospective observational registry capturing consecutive patients hospitalized with COVID-19. We present data on the first 7,868 patients by race/ethnicity treated at 88 hospitals across the US between 01/17/2020 and 7/22/2020. The primary outcome was in-hospital mortality; secondary outcomes included major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, heart failure) and COVID-19 cardiorespiratory ordinal severity score (worst to best: death, cardiac arrest, mechanical ventilation with mechanical circulatory support, mechanical ventilation with vasopressors/inotrope support, mechanical ventilation without hemodynamic support, and hospitalization without any of the above). Multivariable logistic regression analyses were performed to assess the relationship between race/ethnicity and each outcome adjusting for differences in sociodemographic, clinical, and presentation features, and accounting for clustering by hospital. Results: Among 7,868 patients hospitalized with COVID-19, 33.0% were Hispanic, 25.5% were non-Hispanic Black, 6.3% were Asian, and 35.2% were non-Hispanic White. Hispanic and Black patients were younger than non-Hispanic White and Asian patients and were more likely to be uninsured. Black patients had the highest prevalence of obesity, hypertension, and diabetes. Black patients also had the highest rates of mechanical ventilation (23.2%) and renal replacement therapy (6.6%) but the lowest rates of remdesivir use (6.1%). Overall mortality was 18.4% with 53% of all deaths occurring in Black and Hispanic patients. The adjusted odds ratios (ORs) for mortality were 0.93 (95% confidence interval [CI] 0.76-1.14) for Black patients, 0.90 (95% CI 0.73-1.11) for Hispanic patients, and 1.31 (95% CI 0.96-1.80) for Asian patients compared with non-Hispanic White patients. The median OR across hospitals was 1.99 (95% CI 1.74-2.48). Results were similar for MACE. Asian patients had the highest COVID-19 cardiorespiratory severity at presentation (adjusted OR 1.48, 95% CI 1.16-1.90). Conclusions: Although in-hospital mortality and MACE did not differ by race/ethnicity after adjustment, Black and Hispanic patients bore a greater burden of mortality and morbidity due to their disproportionate representation among COVID-19 hospitalizations.

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Racial and Ethnic Differences in Clonal Hematopoiesis, Tumor Markers, and Clinical Outcomes of Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2021-147340 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 402-402

Author(s):

Nancy Gillis ◽

Lauren C Peres ◽

Christelle M Colin-Leitzinger ◽

Mingxiang Teng ◽

Raghunandan Reddy Alugubelli ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Multivariable Analysis ◽

Age At Diagnosis ◽

Advisory Committees ◽

Black Patients ◽

Significant Difference ◽

Hispanic Patients ◽

Race Ethnicity ◽

White Patients

Abstract Background: Multiple myeloma (MM) is twice as common in Blacks compared to Non-Hispanic (NH) Whites and Hispanics. While treatment and mortality differences have been reported for Black patients with MM compared to NH White patients, there is limited data on Hispanic populations. Furthermore, the factors driving observed differences in MM presentation and treatment responses by race and ethnicity are largely unknown. We investigated demographic, clinical, and molecular features, including tumor mutations and clonal hematopoiesis (CH), in a diverse population of patients with MM to elucidate mechanisms driving clinical disparities. Methods: Patients diagnosed with MM who consented to our institutional biorepository protocol were eligible for inclusion. Demographic and clinical data were obtained from cancer registry and abstracted from electronic medical records. MM tumor cells were purified from bone marrow aspirates by CD138 affinity chromatography. DNA was isolated from tumor cells and whole blood for each patient, and whole exome sequencing (WES) data was generated. Tumor somatic mutations were characterized using paired tumor-normal (blood) WES. CH was classified based on blood-derived somatic mutations, using paired tumors and reference populations as germline comparators. Outcomes included overall survival (OS; date of diagnosis to death/last contact) and progression-free survival (PFS; 1 st-line treatment start to 1 st disease progression/death). Results: A diverse group of MM patients (n=496) were included: NH White (80%), NH Black (10%) and Hispanic (9%). NH Black and Hispanic MM patients had a younger median age at diagnosis (57 and 53 yrs, respectively) compared to NH Whites (63 yrs, p = 0.0001; Fig A). There was no statistical difference in treatment categories received by race/ethnicity. NH Black patients had a longer time to hematopoietic cell transplant (HCT; 376 days) than NH White or Hispanic patients (248 and 270 days, respectively, p = 0.011). There was an improvement in OS for NH Black (HR 0.49, 95% CI 0.30-0.81) and Hispanic (HR 0.66, 95% CI 0.37-1.18) patients compared to NH White patients, but the association was not statistically significant in Hispanics. In univariable analysis, OS was also associated with age at diagnosis, International Staging System (ISS), treatment with HCT, and treatment regimen category. In multivariable analysis, after adjusting for age, ISS, HCT, and treatment category there was no longer a statistically significant association between OS and race/ethnicity. Although a worse PFS was present among Hispanic patients (adjusted HR 1.45, 95% CI 0.99-2.13), there was no statistically significant difference in PFS by race/ethnicity. The most mutated genes in MM tumors were KRAS (24%), NRAS (17%), TP53 (11%), DIS3 (9%), and BRAF (9%) (Fig B). Genes with significantly higher tumor mutation rates in Black compared to NH White patients were SP140 (12% v 4%, p = 0.026), AUTS2 (8% v 2%, p = 0.04), and SETD2 (6% v 1%, p = 0.037). IRF4 was most commonly mutated in Hispanics (11% v 3% in NH White and 0% in Black, p = 0.019). We identified CH using WES in 60 (12%) patients. The most CH mutations were in ASXL1, DNMT3A, and TET2. There was no difference in the prevalence of CH by race/ethnicity (p=0.8). There was a statistically significant difference in OS by race/ethnicity and CH status (Fig C). For NH Black patients, CH (HR 4.36, 95% CI 1.36-14.0) and age at diagnosis (HR 1.08, 95% CI 1.03-1.14) were associated with inferior OS (Fig C). After adjusting for age in multivariable analysis, the positive association with CH status among Black patients was no longer statistically significant (HR 2.72, 95% CI 0.48-15.4). A positive, but not statistically significant, association for PFS in NH White patients with CH was also noted (adjusted HR 1.38, 95% CI 0.95-2.0). Conclusions: This is the first study to examine differences in tumor mutation profiles, CH, and treatment among different racial and ethnic groups of patients diagnosed with MM. Our data suggest that age at diagnosis, tumor mutations, and CH may all contribute to clinical disparities observed in patients with MM. Efforts to expand our cohort and incorporate additional molecular biomarkers, epidemiologic characteristics, and clinical parameters are ongoing with the ultimate goal of elucidating targetable biological mechanisms to personalize management and optimize outcomes for diverse patients diagnosed with MM. Figure 1 Figure 1. Disclosures Hampton: M2Gen: Current Employment. Blue: WebMD: Consultancy; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Siqueira Silva: AbbVie Inc.: Research Funding; Karyopharm Therapeutics Inc.: Research Funding. Baz: GlaxoSmithKline: Consultancy, Honoraria; BMS, sanofi, Karyopharm, Janssen, AbbVie: Consultancy, Research Funding; Oncopeptides: Consultancy; Merck: Research Funding. Nishihori: Novartis: Research Funding; Karyopharm: Research Funding. Shain: Janssen oncology: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm Therapeutics Inc.: Honoraria, Research Funding; Sanofi Genzyme: Consultancy, Speakers Bureau; Novartis Pharmaceuticals Corporation: Consultancy; GlaxoSmithLine, LLC: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Adaptive Biotechnologies Corporation: Consultancy, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Increased Disease Burden Among Black Children Compared to White Children with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2018-99-120076 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 369-369

Author(s):

Lena E. Winestone ◽

Kelly D Getz ◽

Yimei Li ◽

Evanette Burrows ◽

Michael Scheurer ◽

...

Keyword(s):

Acute Leukemia ◽

Disease Burden ◽

Vital Signs ◽

Block Group ◽

Black Patients ◽

Hispanic Patients ◽

Race Ethnicity ◽

Racial Ethnic ◽

High Disease Burden ◽

Hispanic White

Abstract Introduction: We previously demonstrated Black patients with acute myeloid leukemia (AML) are more likely to require ICU-level resources at initial presentation. This disparity in acuity at presentation explained 62% of the two-fold racial disparity in early mortality (Winestone Am J Hematol 2017). We sought to expand these findings using a more detailed data source that leverages electronic medical record (EMR) data from two large institutions. We hypothesized that disparities in severity at presentation by race, ethnicity, and socioeconomic status would be identified in granular EMR data for children with acute lymphoblastic leukemia (ALL) and AML. Methods: Acute leukemia patients who were diagnosed at Children's Hospital of Philadelphia or Texas Children's Hospital (2006-2014) were included. Patients who transferred from a referring hospital or whose race was specified as Asian, other, or unknown were excluded. Race and ethnicity were combined into 3 mutually exclusive categories: Hispanic, non-Hispanic White, and non-Hispanic Black. The first set of vital signs (blood pressure, heart rate, respiratory rate, and temperature) and the timing of key diagnostic evaluations were manually abstracted. Patient age, sex, race/ethnicity, residential address, and results of selected laboratory tests from the first 72 hours after admission underwent automated extraction from the EMR. Residential addresses were batch-matched to geo-coordinates linking each patient to a census-derived block group. The following measures of socioeconomic status (SES) were evaluated: median household income, education, unemployment, and crowding. Vital signs were interpreted using age-specific American Heart Association reference ranges. Individual and composite lab-based definitions created a priori were used to identify high disease burden, risk of infection, renal dysfunction, abnormal coagulation (prothrombin time >17 or fibrinogen <100) and liver function (AST/ALT>200 or bilirubin >2.5 or GGT>150). Log-binomial regression was used to compute unadjusted prevalence ratios (PR) and corresponding 95% confidence intervals (CI) comparing incidence of vital sign and laboratory abnormalities by race/ethnicity and block group SES. Stratification by leukemia type (AML vs. ALL) allowed for assessment of heterogeneity in associations of interest. Covariates that were associated with race and thus were potential confounders were also included in multivariable models to obtain adjusted PRs. Results: A total of 899 acute leukemia patients (474 non-Hispanic White, 318 Hispanic, and 107 non-Hispanic Black) were included. Figure 1 shows patient characteristics including patients' geo-coordinates mapped onto census block group median household income. Vital signs at presentation were generally similar across racial/ethnic groups with the exception of heart rate among Hispanic patients (62% vs. 53%, p=0.03). Black patients with AML had an increased prevalence of elevated white blood cell (WBC) count and uric acid and Black patients with ALL demonstrated increased prevalence of coagulopathy compared to White non-Hispanic patients (Table 1). For both AML and ALL, Black patients were more likely to have more than 2 lab abnormalities relative to White non-Hispanic patients. There were no clinically significant differences in time to key diagnostic evaluations by race/ethnicity; median time to CBC was under 2 hours for all racial/ethnic groups, median times to bone marrow biopsy and lumbar puncture ranged from 25-39 hours, and median time to chemotherapy was between 2-3 days. None of the measures of SES were significantly associated with abnormal vital signs, abnormal labs, or prolonged time to key diagnostic evaluations. Conclusions: Black patients with newly diagnosed AML present with increased prevalence of high disease burden as evidenced by elevated WBC and uric acid. Across acute leukemia types, Black patients are more likely to present with more than 2 lab abnormalities; these lab abnormalities likely represent physiologic dysfunction at diagnosis and may compound one another to explain the previously observed racial disparity in ICU-level care requirement. Similar ethnic differences were not observed among Hispanic patients with AML or ALL. We are conducting ongoing investigation into the impact that rurality and distance to the hospital have on initial presentation. Disclosures Fisher: Merck: Research Funding; Pfizer: Research Funding.

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1A Nationwide Analysis of U.S. Racial/Ethnic Disparities in Emergency Department Patients with Mental Health and Substance Use Disorders

10.21203/rs.3.rs-892560/v1 ◽

2021 ◽

Author(s):

Joanne Weinreb ◽

Penina Gavrilova ◽

Jonathan Avery ◽

Sean M. Murphy ◽

Jyotishman Pathak

Keyword(s):

Mental Health ◽

Substance Use ◽

Substance Use Disorders ◽

Wait Time ◽

Wait Times ◽

Hispanic Patients ◽

Racial Ethnic ◽

Triage Level ◽

Hispanic White ◽

White Patients

Abstract BackgroundRacial and ethnic health disparities have been linked with inequalities in access to health care and outcomes. The present study considers whether inequalities persist between racial/ethnic groups among patients with mental health or substance use disorders who visit the emergency department (ED). MethodsWe analyzed data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2012-2018, assessing health disparities among patients diagnosed with mental health or substance use disorders by observing whether significant differences exist in ED wait time and length of visit (LOV) for patients of different races/ethnicities. Stratified models were performed to further understand the impact of regions across the U.S., year, and triage level on the association analysis. ResultsFrom 2012-2018, non-Hispanic Black and Hispanic patients experienced significantly longer ED wait times and LOV as compared to White patients. Patients with private insurance experienced significantly shorter wait times compared to patients with self-pay, and shorter LOV than those with Medicaid/ Children’s Health Insurance Program, or Medicare. Male patients had significantly longer LOV compared to female patients. We observed year by year differences in wait times of non-Hispanic Black patients with improvement appearing between the years 2013 to 2016, while LOV remained consistently longer. We observed both regional and triage level differences, with the U.S. Northeast presenting with the most disparities. Additionally, we noted a general upward trend of SUD diagnoses. Conclusion Our analysis suggests that while there has been an overall improvement in median ED wait time through the years, non-Hispanic Black and Hispanic patients experience significantly longer ED wait time compared to non-Hispanic White patients. Additionally, non-Hispanic Black and Hispanic patients have a significantly longer ED LOV compared to non-Hispanic White patients.

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Contemporary Reevaluation of Race and Ethnicity With Outcomes in Heart Failure

Journal of the American Heart Association ◽

10.1161/jaha.120.016601 ◽

2021 ◽

Vol 10 (3) ◽

Author(s):

Samuel T. Savitz ◽

Thomas Leong ◽

Sue Hee Sung ◽

Keane Lee ◽

Jamal S. Rana ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Pacific Islander ◽

Left Ventricular Ejection ◽

Asian Pacific Islander ◽

Black Patients ◽

Hispanic Patients ◽

Race Ethnicity ◽

Asian Pacific ◽

White Patients

Background Variation in outcomes by race/ethnicity in adults with heart failure (HF) has been previously observed. Identifying factors contributing to these variations could help target interventions. We evaluated the association of race/ethnicity with HF outcomes and potentially contributing factors within a contemporary HF cohort. Methods and Results We identified members of Kaiser Permanente Northern California, a large integrated healthcare delivery system, who were diagnosed with HF between 2012 and 2016 and had at least 1 year of prior continuous membership and left ventricular ejection fraction data. We used Cox regression with time‐dependent covariates to evaluate the association of self‐identified race/ethnicity with HF or all‐cause hospitalization and all‐cause death, with backward selection for potential explanatory variables. Among 34 621 patients with HF, compared with White patients, Black patients had a higher rate of HF hospitalization (adjusted hazard ratio [HR], 1.28; 95% CI, 1.18–1.38) but a lower rate of death (adjusted HR, 0.78; 95% CI, 0.72–0.85). In contrast, Asian/Pacific Islander patients had similar rates of HF hospitalization, but lower rates of all‐cause hospitalization (adjusted HR, 0.89; 95% CI, 0.85–0.93) and death (adjusted HR, 0.75; 95% CI, 0.69–0.80). Hispanic patients also had a lower rate of death (adjusted HR, 0.85; 95% CI, 0.80–0.91). Sensitivity analyses showed that effect sizes for Black patients were larger among patients with reduced ejection fraction. Conclusions In a contemporary and diverse population with HF, Black patients experienced a higher rate of HF hospitalization and a lower rate of death compared with White patients. In contrast, selected outcomes for Asian/Pacific Islander and Hispanic patients were more favorable compared with White patients. The observed differences were not explained by measured potentially modifiable factors, including pharmacological treatment. Future research is needed to identify explanatory mechanisms underlying ongoing racial/ethnic variation to target potential interventions.

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Medicaid Expansion and Racial/Ethnic Differences in Readmission After Acute Ischemic Stroke

INQUIRY The Journal of Health Care Organization Provision and Financing ◽

10.1177/00469580211062438 ◽

2021 ◽

Vol 58 ◽

pp. 004695802110624

Author(s):

Blake T. McGee ◽

Seiyoun Kim ◽

Dawn M. Aycock ◽

Matthew J. Hayat ◽

Karen B. Seagraves ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Low Income ◽

Medicaid Expansion ◽

Percentage Points ◽

Predicted Probability ◽

Hispanic Patients ◽

Race Ethnicity ◽

Racial Ethnic ◽

White Patients

To examine whether rates of 30-day readmission after acute ischemic stroke changed differentially between Medicaid expansion and non-expansion states, and whether race/ethnicity moderated this change, we conducted a difference-in-differences analysis using 6 state inpatient databases (AR, FL, GA, MD, NM, and WA) from the Healthcare Cost and Utilization Project. Analysis included all patients aged 19-64 hospitalized in 2012–2015 with a principal diagnosis of ischemic stroke and a primary payer of Medicaid, self-pay, or no charge, who resided in the state where admitted and were discharged alive (N=28 330). No association was detected between Medicaid expansion and readmission overall, but there was evidence of moderation by race/ethnicity. The predicted probability of all-cause readmission among non-Hispanic White patients rose an estimated 2.6 percentage points (or 39%) in expansion states but not in non-expansion states, whereas it increased by 1.5 percentage points (or 23%) for non-White and Hispanic patients in non-expansion states. Therefore, Medicaid expansion was associated with a rise in readmission probability that was 4.0 percentage points higher for non-Hispanic Whites compared to other racial/ethnic groups, after adjustment for covariates. Similar trends were observed when unplanned and potentially preventable readmissions were isolated. Among low-income stroke survivors, we found evidence that 2 years of Medicaid expansion promoted rehospitalization, but only for White patients. Future studies should verify these findings over a longer follow-up period.

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Genetically Defined Racial Differences Underlie Risk of Relapse in Childhood Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood.v112.11.14.14 ◽

2008 ◽

Vol 112 (11) ◽

pp. 14-14

Author(s):

Jun J. Yang ◽

Wenjian Yang ◽

Cheng Cheng ◽

Meenakshi Devidas ◽

Xueyuan Cao ◽

...

Keyword(s):

Genetic Variation ◽

Acute Lymphoblastic Leukemia ◽

American Indian ◽

American Indians ◽

Lymphoblastic Leukemia ◽

Prognostic Features ◽

Increased Risk ◽

Hispanic Patients ◽

Racial Ethnic ◽

Risk Of Relapse

Abstract The effect of race or ethnicity on cure and survival outcomes among children with acute lymphoblastic leukemia (ALL) is controversial. For those studies that have demonstrated variability in survival associated with race or ethnicity, the cause of these differences remains unclear. We therefore used genome-wide germline single nucleotide polymorphism (SNP) genotypes to quantitatively estimate racial ancestral composition in children with ALL and examined associations between ancestries and the probability of ALL relapse. To infer population genomic structures, we applied principal components analysis (PCA) to genotypes at 219,955 germline SNPs in 893 individuals: 683 patients with ALL (450 from St. Jude Children’s Research Hospital [St. Jude] Total XIIIB and Total XV studies and 233 from Children’s Oncology Group [COG] P9906 protocol), and 210 HapMap samples (60 CEU, 60 YRI, 90 CHB/JPT, serving as references for white, black, and Asian races, respectively). The top ranked principal component (PC1) separated self-reported black patients (n=92) and the YRI HapMap group from all other racial/ethnic groups; PC2 separated self-reported Asian patients (n=19) and the CHB/JPT HapMap samples from non-Asian populations. PC3, on the other hand, primarily captured genetic variation characteristic of American Indian ancestry (assessed using publicly available data from American Indians, n=105). Interestingly, Hispanic patients with ALL (n=75) showed a continuous cline between the American Indians and whites, displaying a gradient of these two ancestries among Hispanics. The relationships between ancestries (PC1, PC2, and PC3) and outcome were assessed in the St. Jude cohort first and validated in the COG cohort, using Fine and Gray’s regression test and after stratification for risk-adapted treatment. Of the top three PCs, only PC3 exhibited a significant association with cumulative incidence of relapse in St. Jude (P=0.038), with higher PC3 values linked to higher risk for relapse. This relationship between PC3 and relapse was validated in the COG cohort (P=0.003), which included more Hispanic patients than the St. Jude cohort. When the St. Jude and COG cohorts were combined, only the American Indian/Hispanic-informative PC3 (not PC1 or PC2) was related to relapse (P=4.5×10−4). Further, PC3 remained significant even after accounting for self-reported race/ethnicity (P=0.044), or when the analysis was restricted to self-reported white patients (P=0.006). The proportions of patients with high risk clinical or biological features (i.e. high leukocyte count, unfavorable age, unfavorable genetic subtypes, and minimal residual disease at the end of induction therapy) did not differ between the high and low PC3 groups (PC3 > or < 0.005). Therefore, the higher relapse rates in patients with higher proportions of American Indian ancestry are not derived from overrepresentation of unfavorable prognostic features in this group. In a multivariate analysis, PC3 remained significantly associated with the risk of relapse (P=0.041) after adjusting for known risk factors, indicating a possible independent prognostic value of PC3. In conclusion, germline genetic variation that is related to American Indian ancestry is associated with increased risk of leukemia relapse, providing evidence for a genetic basis for racial/ethnic differences in cancer treatment outcome.

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Racial Disparities in Nephrology Consultation and Disease Progression among Veterans with CKD: An Observational Cohort Study

Journal of the American Society of Nephrology ◽

10.1681/asn.2018040344 ◽

2018 ◽

Vol 29 (10) ◽

pp. 2563-2573 ◽

Cited By ~ 6

Author(s):

Jonathan Suarez ◽

Jordana B. Cohen ◽

Vishnu Potluri ◽

Wei Yang ◽

David E. Kaplan ◽

...

Keyword(s):

Racial Disparities ◽

Disease Progression ◽

Health Administration ◽

Risk Of Death ◽

Black Patients ◽

Increased Risk ◽

Stage 4 ◽

Ckd Stage ◽

Hispanic Patients ◽

White Patients

BackgroundIncident rates of ESRD are much higher among black and Hispanic patients than white patients. Access to nephrology care before progression to ESRD is associated with better clinical outcomes among patients with CKD. However, it is unknown whether black or Hispanic patients with CKD experience lower pre-ESRD nephrology consultation rates compared with their white counterparts, or whether such a disparity contributes to worse outcomes among minorities.MethodsWe assembled a retrospective cohort of patients with CKD who received care through the Veterans Health Administration from 2003 to 2015, focusing on individuals with incident CKD stage 4 who had an initial eGFR≥60 ml/min per 1.73 m2 followed by two consecutive eGFRs<30 ml/min per 1.73 m2. We repeated analyses among individuals with incident CKD stage 3. Outcomes included nephrology provider referral, nephrology provider visit, progression to CKD stage 5, and mortality.ResultsWe identified 56,767 veterans with CKD stage 4 and 640,704 with CKD stage 3. In both cohorts, rates of nephrology referral and visits were significantly higher among black and Hispanic veterans than among non-Hispanic white veterans. Despite this, both black and Hispanic patients experienced faster progression to CKD stage 5 compared with white patients. Black patients with CKD stage 4 experienced slightly lower mortality than white patients, whereas black patients with CKD stage 3 had a small increased risk of death.ConclusionsBlack or Hispanic veterans with CKD are more likely than white patients to see a nephrologist, yet are also more likely to suffer disease progression. Biologic and environmental factors may play a bigger role than nephrology consultation in driving racial disparities in CKD progression.

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Impact of Ethnicity on Toxicities Associated with Dose Escalating Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood-2019-130268 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5074-5074

Author(s):

Ashley Siryk ◽

Haley Grunwald ◽

Amanda Brahim ◽

Frank Gentile ◽

Faina Shenderov ◽

...

Keyword(s):

Sample Size ◽

Primary Outcome ◽

Lymphoblastic Leukemia ◽

Hispanic Patients ◽

Pediatric All ◽

Grade 3 ◽

The Impact ◽

Dose Escalating ◽

Hispanic White ◽

White Patients

Background: Epidemiologic studies in pediatric oncology have demonstrated disparities in Acute Lymphoblastic Leukemia (ALL) outcomes and survival for various ethnic minorities including Hispanic patients. While differences between outcomes and survival of different racial/ethnic groups in pediatric ALL is well documented, the impact of race/ethnicity on the incidence of methotrexate related toxicities in this population has not been fully described. Methotrexate, a mainstay of pediatric ALL regimens, has the potential to cause a variety of toxicities including myelosuppression, hepatic injury, acute kidney injury (AKI), mucositis, and central nervous system (CNS) injury. Recent literature suggests that Hispanic ethnicity may be associated with an increased risk of methotrexate toxicity, specifically neurotoxicity (Giordano (2017)). This project evaluated ethnicity associated with the incidence of methotrexate toxicities that could lead to dose reduction or delays in therapy such as grade 3 or 4 myelosuppression, hepatic injury, nephrotoxicity, and mucositis in patients receiving dose escalating methotrexate. Methods: A single-center, retrospective chart review was conducted at a 224 bed pediatric hospital. Patients were eligible for inclusion if they had a diagnosis of ALL and received intravenous (IV) dose escalating methotrexate between August 1, 2011 and March 31, 2019. Electronic medical records were used to identify eligible patients using medication identification numbers cross referenced with diagnosis codes. Toxicity data was collected to evaluate interruption in dose escalation of IV methotrexate due to grade 3 or 4 liver dysfunction, nephrotoxicity, mucositis, neutropenia, or thrombocytopenia. The primary outcome was percentage of doses which resulted in a dose-limiting toxicity. A two-sample t-test was performed for the primary outcome between Hispanic white and non-Hispanic white patients. Results: Of the 64 patients initially identified, 60 patients were included for final analysis. Two patients were excluded due to a diagnosis of Acute Biphenotypic Leukemia, one patient did not receive IV methotrexate per protocol due to delay in therapy and was subsequently ineligible, and one patient did not receive dose escalating methotrexate per protocol for unspecified reasons. A total of 460 doses were given to 60 patients. The sample size consisted of 22 non-Hispanic white, 21 Hispanic white, 9 Black, 3 Hispanic black, 1 Asian, 1 multi-racial, and 3 patients with unspecified ethnicity. The percentage of patients who experienced at least one toxicity was 58.3% (35 patients). The most common grade 3 or 4 toxicity experienced per dose was thrombocytopenia (6.5%), followed by neutropenia (6.3%), mucositis (1.3%), liver dysfunction (0.22%), and no patient experienced nephrotoxicity. When comparing the rate of toxicity between Hispanic and non-Hispanic patients, Hispanic patients experienced toxicity at a rate of 17.4% per dose compared to non-Hispanic patients at 12.2% per dose, although this was not a statistical significant difference (p = 0.61). Hispanic white and non-Hispanic white patients received the same amount of doses at 165 doses of IV methotrexate. Hispanic white patients experienced a toxicity rate of 19.4% per dose compared to 12.1% per dose in the non-Hispanic white patients. Hispanic white patients experience more thrombocytopenia, where as non-Hispanic white patients experienced more neutropenia. Although not statistically significant possibly due to small sample size, Hispanic ethnicity was associated with higher rates of methotrexate toxicities. Understanding the impact of methotrexate toxicity in respect to ethnicity is important to improving treatment outcomes for pediatric patients with ALL. More robust studies with a larger sample size are warranted to explore the potential impact of ethnicity on tolerability of this regimen. Disclosures No relevant conflicts of interest to declare.

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Characteristics and Factors Associated with COVID-19 Infection, Hospitalization, and Mortality Across Race and Ethnicity

10.1101/2020.10.14.20212803 ◽

2020 ◽

Author(s):

Chengzhen L. Dai ◽

Sergey A. Kornilov ◽

Ryan T. Roper ◽

Hannah Cohen-Cline ◽

Kathleen Jade ◽

...

Keyword(s):

Mechanical Ventilation ◽

Hospital Mortality ◽

Health System ◽

Alaska Native ◽

Clinical Characteristics ◽

Hospital Death ◽

Increased Risk ◽

Hispanic Patients ◽

Race Ethnicity ◽

Racial Ethnic

BackgroundData on the characteristics of COVID-19 patients disaggregated by race/ethnicity remain limited. We evaluated the sociodemographic and clinical characteristics of patients across the major racial/ethnic groups and assessed their associations with COVID-19 outcomes.MethodsThis retrospective cohort study analyzed patients who were tested for SARS-CoV-2 in a large, integrated health system spanning California, Oregon, and Washington between March 1 and August 30, 2020. Sociodemographic and clinical characteristics were obtained from electronic health records. Odds of SARS-CoV-2 infection, COVID-19 hospitalization, and in-hospital death were assessed with multivariate logistic regression.Findings289,294 patients with known race/ethnicity were tested for SARS-CoV-2 by PCR, of whom 27.5% were non-White minorities. 15,605 persons tested positive, with minorities representing 58.0%. Disparities were widest among Hispanics, who represented 40.5% of infections but 12.8% of those tested. Hispanics were generally younger and had fewer comorbidities except diabetes than White patients. Of the 3,197 patients hospitalized, 58.9% were non-White. 459 patients died, of whom 49.8% were minorities. Racial/ethnic distributions of outcomes across the health system tracked with state-level statistics. Increase odds of testing positive and hospitalization were associated with all minority races/ethnicities except American Indian/Alaska Native. Highest odds of testing SARS-CoV-2 positive was for Hispanic patients (OR [95% CI]: 3.68 [3.52-3.84]) and highest odds of COVID-19 hospitalization was for Native Hawaiian/Pacific Islander patients (2.13 [1.48 - 3.06]). Hispanic patients also exhibited increased morbidity including need for mechanical ventilation. In multivariate modeling, Hispanic race/ethnicity was associated with increased odds of hospital mortality (1.75 [1.15-2.67]) among patients over age 70, but hospital mortality was not increased for any race/ethnicity sub-population in the multivariate model.InterpretationMajor healthcare disparities were evident, especially among Hispanics who tested positive at a higher rate, and despite younger in age, required excess hospitalization and need for mechanical ventilation compared to their expected demographic proportions. As characteristics of patients varying between race/ethnicity, targeted, culturally-responsive interventions are needed to address the increased risk of poor outcomes among minority populations with COVID-19.FundingBiomedical Advanced Research and Development Authority; National Center for Advancing Translational Sciences

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