Summary Acute lymphoblastic leukemia (ALL) is the most common cancer in children and, although cure rates have improved over the past 50 years, ethnic disparities persist. In particular, Latinos have the highest incidence and among the lowest survival rates for leukemia in the U.S. The underlying causes of this disparity are multi-factorial, including differences in tumor and host biology, as well as social/behavioral factors such as limited healthcare access. Host pharmacogenomics and other biological factors resulting in increased treatment-related toxicities are a key and under-studied cause of ethnic disparities in outcomes. Adverse outcomes result both from direct treatment-associated morbidity and mortality, and from compromised ability to deliver sufficiently intensive anti- leukemic therapy. The overall goals of this P20 program are to reduce outcome disparities among Latino children and adolescents by identifying host biological factors that result in increased toxicities, and to lay the groundwork for establishment of the first Specialized Programs of Research Excellence (SPORE) devoted to pediatric leukemia. The two primary Research Projects will identify factors associated with risk for two key treatment-related toxicities, hepatotoxicity and neurotoxicity, which adversely impact treatment outcomes and occur disproportionately in Latinos. The eventual SPORE will expand upon this work by (1) pursuing prevention and treatment strategies and (2) investigating ethnic disparities in other clinically impactful treatment-related toxicities. The Program will be administered through the Administrative Core (Core A). Biospecimens will be processed by Core B, and statistical analysis will be provided by Core C. A Developmental Research Program will foster development of innovative pilot projects that aim to understand and/or reduce ethnicity-based disparities in ALL outcomes. We will leverage the Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium, comprising 6 cancer centers in the southwestern U.S., which will provide clinical data from 3,000 and clinical data, bone marrow, blood and cerebrospinal fluid samples from nearly 2,000 children and adolescents with newly diagnosed ALL for the following two novel and integrated Projects. Our synergistically integrated team will define key biological factors associated with hepatotoxicity and neurotoxicity, important contributors to ethnic outcome disparities. More broadly, this Program will further strengthen and expand the REDIAL Consortium, with its invaluable ethnically diverse dataset and biorepository, and model its use for development of risk prediction models that identify Latino patients at risk for toxicities and illuminate the underlying biology mechanisms. This work will form the foundation for a future SPORE that will investigate additional toxicities of ALL therapy, and translate these findings into development of effective intervention strategies. This efficient monetary in...