Neighborhood disparities and treatment outcomes in pediatric acute lymphoblastic leukemia (ALL): A report from the REDIAL Consortium

Introduction- Acute lymphoblastic leukemia (ALL), the most common pediatric cancer, shows persistent outcomes disparities among socioeconomically disadvantaged and Hispanic children. Structural factors such as neighborhood socioeconomic status (nSES) and residence in Hispanic enclaves - culturally distinct neighborhoods with high concentrations of Hispanic residents, linguistically isolated households, and ethnic resources - may influence cancer outcomes, yet their impact on pediatric ALL remains unclear. We examined associations of nSES and Hispanic enclave residence with treatment outcomes in children with ALL. Methods- The REducing Disparities in Acute Leukemia (REDIAL) Consortium includes six pediatric cancer centers across Texas. We included children (0-24 years) diagnosed with ALL between 2005-2017 and treated at centers in Houston, Fort Worth, and McAllen. Census tract Hispanic enclave and nSES (Yost) indices were computed from U.S. Census and American Community Survey data. We defined Hispanic enclaves as tracts in the highest quintile (Q5) or Q4 adjacent to Q5 with >250 Hispanic residents, and low nSES as tracts in the lowest two quintiles of statewide distribution, using patient addresses at the time of diagnosis. Outcomes included end-of-induction (EOI) minimal residual disease (MRD) positivity (≥0.01%), relapse, event-free survival (EFS), and overall survival (OS). Associations were evaluated using logistic and Cox regression models adjusted for sex, age at diagnosis, race/ethnicity, NCI risk group, ALL immunophenotype, cytogenetic subtype, and treating institution. Results- Among 1,348 patients, 41% resided in low nSES tracts and 42% in Hispanic enclaves; 59% were Hispanic and 90% had B-ALL. Median follow-up was 5.6 years for EFS and 5.2 years for OS. In adjusted analyses, neither enclave residence (aOR= 1.22; 95% CI= 0.82, 1.80) nor low nSES (aOR= 1.06; 95% CI= 0.73, 1.55) were associated with EOI MRD positivity; similar null associations were observed for relapse (enclave: aOR= 0.88; 95% CI= 0.52, 1.49; low nSES: aOR= 1.04; 95% CI= 0.66, 1.64), EFS (enclave: aHR= 0.81; 95% CI= 0.52, 1.26; low nSES: aHR= 1.04; 95% CI= 0.71, 1.54), and OS (enclave: aHR= 1.07; 95% CI= 0.59, 1.94; low nSES: aHR= 0.89, 95% CI= 0.53, 1.51). Although unadjusted analyses indicated slightly poorer 5-year EFS for low nSES areas (81% vs. 85%, p=0.04), this difference attenuated after adjustment. Conclusions- In this large, multi-center, and diverse cohort of children with ALL, neighborhood socioeconomic disadvantage and residence in Hispanic enclaves were not independently associated with treatment outcomes after accounting for clinical and cytogenetic features. Future studies should examine other social determinants and the influence of neighborhood context on disease characteristics, survivorship, and late effects.