Risk of Psychopathology and Neurocognitive Impairment in Leukemia Survivors

• Neurocognitive assessment of attention, processing speed, and executive functions. [ Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment ] [ Designated as safety issue: No ]
  

• Quantitative magnetic resonance imaging (MRI) and DTI and functional magnetic resonance imaging (fMRI) of brain structure and function. [ Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment ] [ Designated as safety issue: No ]
  
• Family and parental stress as reported by primary caregiver. [ Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment ] [ Designated as safety issue: No ]
  
• Associations between genetic polymorphisms in key enzyme pathways and higher order brain development in long-term survivors of pediatric ALL. [ Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment ] [ Designated as safety issue: No ]
  
• Associations between fatigue and neurocognitive performance and between sleep problems and neurocognitive performance. [ Time Frame: Once, at least 5 years post ALL diagnosis and 2 years off treatment ] [ Designated as safety issue: No ]
  

Survival rates for pediatric acute lymphoblastic leukemia (ALL) now exceed 80%. With this growing population of long-term survivors comes recognition that a considerable proportion experience one or more significant late effects. For children undergoing central nervous system (CNS) treatment, common late effects include neurocognitive impairment and neurobehavioral problems. Although these problems first manifest as subtle difficulties with attention and processing speed, they can evolve into deficits in higher order brain functions that significantly impact functional skills in a subset of long-term survivors. There currently is no method to accurately identify patients at greatest risk for these long-term behavioral and neurocognitive problems. Through this proposal, this study plans to utilize existing data collected during acute treatment to identify predictors of long-term neurocognitive and brain maturation outcomes. The study also proposes to collect data on attention-deficit/hyperactivity disorder (ADHD) and associated comorbidities, higher order executive functions, and structural and functional brain imaging in survivors who are at least 8 years of age and greater than 5 years from diagnosis.

All patients will undergo a single neurocognitive evaluation focused on assessment of higher order executive functions. Patients will be evaluated during their regularly scheduled annual follow-up visit, when health-related monitoring will also occur. Parents of participants will be asked to complete questionnaires designed to assess the family environment and the impact of cancer diagnosis on family functioning and parent stress.

Brain Imaging: To better demonstrate untoward treatment effects upon cortical brain development, quantitative MR imaging of myelin integrity using diffusion tensor imaging (DTI) and cortical thickness assessment using high resolution volumetric imaging will be utilized. All patients will also be evaluated using functional MRI (fMRI) procedures during resting state and participation in attention and working memory tasks. fMRI and DTI data will be de-identified then analyzed at MD Anderson Cancer Center in Houston, Texas.