Date of Award
Doctor of Philosophy
Vikki G Nolan
James G Gurney
Contemporary chemotherapy results in a greater than 90% five-year survival rate from childhood acute lymphoblastic leukemia (ALL). However, long-term survivors of childhood ALL still present with a higher prevalence of neurocognitive function problems, specifically executive function deficits, and behavior emotional problems compared to the general population. We conducted two epidemiologic studies of these issues and a Phase II clinical trial to improve executive deficits among long-term childhood ALL survivors. First, we evaluated the association between sustained attention and parent-rated behavioral inattention at the end of chemotherapy, and neurocognitive outcomes at long-term follow-up (LTFU). Patients demonstrated higher frequency of impairment in sustained attention (range 38 - 56%) and behavior inattention (20%) at the end of therapy, and executive function deficits (range 21-54%) at LTFU, compared to national norms. Survivors improved on measures of sustained attention at LTFU. Chemotherapy exposure predicted outcomes at both time points, which suggests early therapeutic interventions on neurocognitive function. Next, we examined the prevalence and pattern of parent- and self-reported child behavioral and emotional symptoms and mental health disorders at LTFU, and the impact of parent self-reported emotional distress and post-traumatic stress symptoms (PTSS) on the report of child’s outcome. Symptoms reported were consistent between child and parent on inattention (28% and 24%), and Oppositional Defiant Disorder (20% and16%). A high proportion of anxiety disorders reported by parents were significantly associated with parent self-reported emotional distress and PTSS rather than with survivors’ self-report of anxiety symptoms, which suggests that emotional distress in parents should be taken into consideration for preventative intervention targeting behavioral outcomes in survivors of childhood ALL. In the final study, we designed and conducted a Phase II trial combining Transcranial Direct Current Stimulation (tDCS) and cognitive training to evaluate feasibility and potential efficacy of tDCS on improving executive function. Participants were adult survivors of ALL with executive function deficits. After 5-weeks of self-administered remote sessions, tDCS showed marginal clinically meaningful effect sizes with low adverse event rate. These findings suggest a larger randomized clinical trial tDCS may be warranted.
Dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.
Liu, Wei, "Long-term Neurocognitive, Behavior and Emotional Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated with Chemotherapy Only" (2017). Electronic Theses and Dissertations. 1777.