Project 4: Disparities in patient-reported outcomes, epigenetic profiles, and neighborhood social determinants of health in childhood acute lymphoblastic leukemia (ALL)

Despite significant improvements in ALL outcomes in the past decades, Latino children with ALL continue to experience inferior survival, excess toxicity, and higher rates of relapse. Health outcome disparities have multifactorial root causes, such as differences in disease biology, host factors related to cancer susceptibility and response to treatment, or exposure to a broad spectrum of social determinants of health (SDoH). SDoH include individual and neighborhood factors, as well as factors related to access to care and infrastructure. SDoH disproportionately affect Latinos, particularly non-English speakers, and are major contributors to health risks and outcomes; lower socioeconomic status is significantly associated with greater risk for relapse and poorer overall survival in childhood ALL, as is residence in an ethnic enclave with individuals that share a similar background and language. Few studies conducted in childhood cancer populations collect SDoH data, and less than 10% measure patient-reported outcomes (PROs). Moreover, there is evidence that epigenetics are a potential mechanism linking childhood neighborhood environment and adult health, with changes in DNA methylation observed in association with excess morbidity and mortality related to chronic diseases, including cancer. Our proposal leverages PROs, biospecimens, and adverse event data prospectively collected from a diverse, multi-institutional study in Texas and California (the Reducing Ethnic Disparities in Acute Leukemia consortium, REDIAL), and will also include PRO data from the NCI-supported UG3/UH3 survivor cohort of REDIAL sites to assess symptoms and health-related quality of life (HRQOL) across the cancer care continuum. Our overarching objective is to identify associations between SDoH, PROs, and corresponding molecular profiles of Latino and non-Latino children with and without neighborhood disadvantage, and to use these data to tailor an on-treatment psychosocial intervention for Latino children impacted by SDoH. We hypothesize that Latino children with ALL will report excess symptoms interfering with daily activities and poorer HRQOL, which will be related to SDoH, correspond with specific epigenetic profiles, and be modifiable through psychosocial intervention. Aim 1 will collect PRO data at three on-treatment time points and in survivorship using validated measures (PED-PRO-CTCAE and PROMIS) and will assess the relationship between SDoH and PROs in a diverse cohort of children with ALL. Aim 2 will evaluate the relationship between SDoH-associated epigenetic profiles and PROs in Latino and non-Latino children with ALL. Aim 3 will leverage PRO data and stakeholder engagement strategies to tailor a psychosocial support intervention for Latino children with ALL affected by SDoH and will then prospectively assess intervention feasibility and acceptability in the target population. Our innovative proposal addresses a critical unmet need to evaluate and mitigate outcome disparities in vulnerable populations disproportionately impacted by SDoH, informing future investigations with the long-term objective of achieving health equity in Latino children treated for ALL.