Evolution of neurocognitive function in long-term survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only
Abstract
Purpose: The purpose of this study was to determine the evolution of neurocognitive problems from therapy completion to long-term follow-up in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. Methods: We evaluated whether attention problems observed at therapy completion evolve into long-term executive dysfunction in 158 survivors treated on a single institution protocol. Treatment data (high-dose intravenous methotrexate exposure [serum concentration] and triple intrathecal chemotherapy injections) were collected. Parent report of behavior and direct cognitive testing of survivors was conducted at end of therapy, and survivors completed neurocognitive testing when > 5 years post-diagnosis. Results: At the end of chemotherapy, survivors (52% female; mean age 9.2 years) demonstrated higher frequency of impairment in sustained attention (38%) and parent-reported inattention (20%) compared to population expectations (10%). At long-term follow-up, survivors (mean age 13.7 years; 7.6 years post-diagnosis) demonstrated higher impairment in executive function (flexibility 24%, fluency 21%), sustained attention (15%), and processing speed (15%). Sustained attention improved from end of therapy to long-term follow-up (p < 0.001). Higher methotrexate AUC and greater number of intrathecal injections were associated with attention problems (p = 0.009, p = 0.002, respectively) at the end of chemotherapy and executive function (p < 0.001, p = 0.02, respectively) problems at long-term follow-up. Attention problems at the end of therapy were not associated with executive function problems at long-term follow-up (p’s > 0.05). The direct effect of chemotherapy exposure predicted outcomes at both time points. Conclusions and Implications for Cancer Survivors: Survivors should be monitored for neurocognitive problems well into long-term survivorship, regardless of whether they show attention problems at the end of therapy. Treatment exposures are the best predictor of long-term complications.
Publication Title
Journal of Cancer Survivorship
Recommended Citation
Liu, W., Cheung, Y., Conklin, H., Jacola, L., Srivastava, D., Nolan, V., Zhang, H., Gurney, J., Huang, I., Robison, L., Pui, C., Hudson, M., & Krull, K. (2018). Evolution of neurocognitive function in long-term survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. Journal of Cancer Survivorship, 12 (3), 398-406. https://doi.org/10.1007/s11764-018-0679-7
