Reducing Ethnic Disparities in Acute Leukemia (REDIAL)

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and, although cure rates have improved over the past 50 years, population-based 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 disease biology, host factors related to susceptibility and treatment response, and exposure to a broad spectrum of social determinants of health (SDoH). Host pharmacogenomics and epigenetics, and other biological factors resulting in increased treatment-related toxicities are key and under-studied causes of population-based 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 U54 program are to reduce outcome disparities among Latino children and adolescents with ALL by identifying biological and SDoH factors that result in adverse outcomes. Notably, this program will constitute the first Specialized Programs of Research Excellence (SPORE) devoted to pediatric leukemia. The four Research Projects will identify multifactorial etiologies of disparities in outcomes in Latinos, including factors associated two key treatment-related toxicities, hepatotoxicity (Project 1) and methotrexate-associated neurotoxicity (Project 2); pharmacogenomics (Project 3); and patient-reported outcomes, epigenetics, and SDoH (Project 4). The ultimate goal of this SPORE is to pursue prevention and treatment strategies aimed at reducing population-based disparities in all these areas. 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. Core D will facilitate community outreach and engagement. A Developmental Research Program will foster development of innovative pilot projects that aim to understand and/or reduce population-based disparities in ALL outcomes, and a Career Enhancement Program will recruit, train, and guide an unselected, population-based group of physicians and scientists to become successful translational investigators focusing on population-based disparities in outcomes in pediatric ALL. We will leverage the REducing Disparities in Acute Leukemia (REDIAL) Consortium, comprising 6 cancer centers in the southwestern U.S., to generate a rich population-based dataset derived from over 7,000 children and adolescents with de novo ALL (over 6,000 existing and 1,000 to be added during the current study), and a biorepository of bone marrow, blood, buccal cells, and cerebrospinal fluid samples from nearly 2,000 subjects. This invaluable resource will also serve as an important asset for current and future investigations of factors associated with disparities in ALL toxicities and outcomes. This work will form the foundation for development of effective risk prediction and intervention strategies to reduce outcome disparities in Latino children and adolescents with ALL.