PROJECT SUMMARY/ABSTRACT Latino children experience increased incidence of acute lymphoblastic leukemia (ALL), as well as disparities in treatment response, relapse, and survival. However, to date, there have been few studies evaluating the impact of persistent neurocognitive symptoms on educational and economic outcomes in Latino survivors. What has been demonstrated by our group and others is that disparities among Latino children with ALL are not fully explained by non-genetic factors, such as differences in treatment adherence. In fact, biological factors contribute to these outcomes: Native American genetic ancestry has been implicated in relapse among Latinos with ALL and is related to neurotoxicity during treatment. Building from this work, we explore two unanswered questions: 1) what is the burden of neurocognitive deficits among Latino children diagnosed with ALL relative to non-Latino children, and 2) what is the relative contribution of clinical, socioeconomic, cultural, and biological factors in explaining neurocognitive disparities among childhood ALL survivors. We will leverage our ongoing Reducing Ethnic Disparities in Acute Leukemia (REDIAL) cohort to conduct deep neurocognitive phenotyping in a subset of the population (N=400) diagnosed and treated for ALL – with a particular focus on Latinos, who make up more than 50 percent of the ongoing cohort. We will model neurocognitive performance from diagnosis through 7 years post-diagnosis by employing an accelerated longitudinal cohort design, which includes annual assessments for: 1) newly diagnosed patients in the first years of the grant (Wave 1, n = 200); and 2) survivors who are 3-7 years post diagnosis (Wave 2, n = 200). We also incorporate factors that have yet to be included in models of neurocognitive outcomes among children diagnosed with ALL, such as measures of socioeconomic status (SES), acculturation, English-language proficiency, and genetic ancestry. Our research aims are to: 1) characterize the trajectory of neurocognitive performance in Latino children diagnosed with ALL; 2) examine the impact of clinical, individual and neighborhood socioeconomic factors, and level of acculturation among Latinos; and 3) assess the relative contribution of genetic ancestry to neurocognitive performance in children diagnosed with ALL. Strengths of our approach include rigorous preliminary data, a recruitment infrastructure for enrolling Latino patients diagnosed with ALL, existing data and samples collected as part of our ongoing REDIAL cohort, an unparalleled research environment, and a geographical region that is ethnically and socioeconomically diverse. This proposal has significant translational potential to improve the clinical management of neurocognitive outcomes in this population, as it will identify children at risk for neurocognitive difficulties and in greatest need of intervention, critical points in treatment/survivorship when intervention strategies may help to mitigate disparities in neurocognitive outcomes, and targets for intervention.

PROJECT NARRATIVE Latino children experience increased incidence of acute lymphoblastic leukemia (ALL), as well as disparities in ALL treatment toxicities, relapse, and survival – however, less is known about neurocognitive outcomes in Latino survivors, which has important implications for educational attainment and quality of life. The proposed study will employ an accelerated longitudinal cohort design to examine for the first time ever 1) the extent to which neurocognitive response to ALL chemotherapy differs by ethnicity; and 2) the relative contribution of clinical, socioeconomic, cultural, and biological variability in explaining neurocognitive disparities among childhood ALL survivors. This line of research is well-poised to identify: a) subpopulations of youth at greatest risk for neurocognitive difficulties and in greatest need of intervention; b) critical points in treatment/survivorship to employ intervention strategies to mitigate disparities in neurocognitive outcome; and c) potential targets for intervention.