DNA, Disparities, and Delays in Care: An Investigation of Genetic and Social Contributors to Adverse Outcome in Pediatric Acute Lymphoblastic Leukemia

Abstract

Although pediatric Acute Lymphoblastic Leukemia (ALL) survival has increased over the past 70 years, event free survival (EFS) can vary significantly based on genetic variables such as molecular subtype, and social variables such as race. While some studies have attempted to explain the EFS racial disparity in ALL by investigating social determinants of health such as socioeconomic status (SES), insurance, and compliance, others have incorrectly credited genetic racial differences. To this end, I discussed the terminological confusion in the literature around race-related variables as well as the historical precedents and modern social variables that may influence racial disparities in ALL. Further the Fragile Families Child Wellbeing study was used to investigate the credibility of claims regarding differential disease susceptibility by ancestry, revealing no significant associations between disease loci and ancestry. Next, the Pediatric Health Information System database was utilized to investigate the relationship between race and severity of illness when children are diagnosed with primary and/or relapsed ALL and revealed a significant association between severity of illness with race and age. To my knowledge this is the first documentation of this aspect of disparity in pediatric ALL. Lastly, the Therapeutically Applicable Research to Generate Effective Treatment database was used to investigate the prognostic significance of age, white blood cell count, race, and copy number variants (CNV) in event free survival. Seven new and significant CNV regions were identified solely in patients with adverse outcome, of which, deletions on chromosome 14 significantly overlapped T-cell receptor 7 and improved EFS. Together these findings contribute to our understanding of factors that influence event free survival in ALL and will hopefully lead to improved outcomes for all patients.