Chemotherapy Pharmacodynamics and Neuroimaging and Neurocognitive Outcomes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia

作者：Kevin R. Krull, Yin Ting Cheung, Wei Liu, Slim Fellah, Wilburn E. Reddick, Tara M. Brinkman, Cara Kimberg, Robert J. Ogg, Deo Kumar Srivastava, Ching‐Hon Pui, Leslie L. Robison, Melissa M. Hudson · 发表于：Journal of Clinical Oncology · 年份：2016 · DOI：10.1200/jco.2015.65.4574 · 被引用次数：137 · 研究领域：Cancer-related cognitive impairment studies、Acute Lymphoblastic Leukemia research、Childhood Cancer Survivors' Quality of Life

PURPOSE: To examine associations among methotrexate pharmacodynamics, neuroimaging, and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy-only protocol. PATIENTS AND METHODS: This longitudinal study linked pharmacokinetic assays collected during therapy to neurocognitive and brain imaging outcomes during long-term follow-up. A total of 218 (72.2%) of 302 eligible long-term survivors were recruited for outcome studies when they were more than 5 years post-diagnosis and older than 8 years of age. At long-term follow-up, survivors were an average of 13.8 years old and 7.7 years from diagnosis, and 51% were male. Neurocognitive testing, functional magnetic resonance imaging (MRI) during an executive function task, and structural MRI with diffusion tensor imaging were conducted. Generalized linear models were developed to identify predictors, and models were adjusted for age at diagnosis, sex, and parent education. RESULTS: Intelligence was within normal limits (mean, 98; standard deviation, 14) compared with population expectations (mean, 100; standard deviation, 15), though measures of executive function, processing speed, and memory were less than population means (all P < .02 after correction for false discovery rates). Higher plasma concentration of methotrexate was associated with a poorer executive function score (P < .02). Higher plasma methotrexate was also associated with higher functional MRI ...