1. This study will evaluate the association between changes in basic cognitive and behavioral functioning by the end of chemotherapy treatment, and the later development of higher order executive functions in pediatric acute lymphoblastic leukemia (ALL).
2. The association between acute treatment-related changes in brain integrity and subsequent brain maturation in long-term survivors of pediatric ALL will be evaluated.
3. The association between patterns of behavioral and executive dysfunction and brain maturation in long-term survivors of pediatric ALL will be examined.
4. The association between genetic polymorphisms in key enzyme pathways and higher order brain development in long-term survivors of pediatric ALL will be explored.
5. The associations between biologic and behavioral indices of fatigue/sleep and higher order brain development in long-term survivors of pediatric ALL will be explored.

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.

Inclusion Criteria:

• Enrolled on SJCRH TOTXV ALL protocol
• ≥ 5 years post diagnosis of ALL
• ≥ 8.0 years of age at time of follow-up evaluation

Exclusion Criteria:

• History of cranial or total-body radiation therapy
• History of bone marrow transplant
• History of relapse
• History of head injury, neurological condition unrelated to ALL treatment, or diagnosis of a genetic disorder associated with neurocognitive impairment (e.g. Down Syndrome)

Children originally enrolled and treated on the SJCRH TOTXV protocol. The study has reviewed TOTXV patient database and has identified 343 patients (189 males and 154 females) who will meet the inclusion criteria (assuming no additional deaths or relapse).