Neurocognitive Sequelae in Adult Childhood Leukemia Survivors Related to Levels of Phosphorylated Tau

• Published in: JNCI : Journal of the National Cancer Institute 2017-07, Vol.109 (7)
• Main Authors: Elens, Iris, Deprez, Sabine, Danckaerts, Marina, Bijttebier, Patricia, Labarque, Veerle, Uyttebroeck, Anne, Van Gool, Stefaan, D'Hooge, Rudi, Lemiere, Jurgen
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antimetabolites, Antineoplastic - adverse effects; Biomarkers - cerebrospinal fluid; Case-Control Studies; Cognition Disorders - cerebrospinal fluid; Cognition Disorders - chemically induced; Cognition Disorders - pathology; Cross-Sectional Studies; Female; Humans; Lymphoma, Non-Hodgkin - drug therapy; Male; Methotrexate - adverse effects; Neuropsychological Tests; Phosphorylation; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Prognosis; Retrospective Studies; Survival Rate; Survivors; tau Proteins - cerebrospinal fluid; Young Adult
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/djw321

Central nervous system-directed prophylactic chemotherapy increases survival in childhood leukemia, but possible late neurocognitive sequelae remain a concern. We compared intellectual performance (WAIS IV), memory (AVLT), and executive functioning (ANT) between adult leukemia survivors (n = 31) and control individuals (n = 35). In survivors, cerebrospinal fluid (CSF) levels of phosphorylated Tau (p-Tau) during treatment and total intrathecal methotrexate dose correlated with adult intellectual performance (Pearson's and Spearman's coefficients, respectively). Long-term memory and attentional control, both maturing before survivors' mean age at diagnosis, were unaffected (P > .05 on all four subtests), in contrast to cognitive flexibility and information processing (P < .05 for eight of the subtests), which mature during adolescence. CSF p-Tau and methotrexate dose negatively correlated with intellectual performance (r = -0.414, P = .04 and r = -0.484, P = .007, respectively), but not with each other (r = 0.219, P = .29). These data identify CSF p-Tau as a predictor of late neurocognitive sequelae (in addition to methotrexate dose). Early identification of children at risk could inspire interventions to prevent or remediate chemotherapy-induced cognitive sequelae.