Abstract
Children acquire neuropsychologic dysfunctions after chemotherapy for hematologic malignancy. In this study, putative changes in levels of CSF-tau (a marker of neural dysintegrity) in leukemic children prior to and during chemotherapy were studied. Cerebrospinal fluid (CSF) samples were obtained before and during treatment from patients with B cell non-Hodgkin's lymphoma (NHL, n = 10), non-B cell acute lymphoblastic leukemia/NHL (non-B-ALL, n = 48), acute myeloid leukemia (AML, n = 9), other malignant diseases (n = 9), and six control children. a sandwich-type elisa (innotest htau-ag) was used for measuring csf-tau. sixteen out of 50 patients with hematological malignancies, including the patients with proven leukemic cns invasion, already showed high csf-tau levels at baseline (>300 pg/ml). The pre-induction treatment for non-B-ALL, consisting of only corticosteroids and methotrexate (MTX), resulted in a significant increase of tau at day 8 (on average to 535 pg/ml). Larger increases as compared to baseline levels of CSF-tau were observed in patients treated for B-NHL with systemic vincristine, corticosteroids and cyclophosphamide, and intrathecal MTX (mean 776 pg/ml at day 8). In two AML patients with CNS invasion, CSF-tau increased during chemotherapy up to 1500 and 948 pg/ml, respectively. In one non-B-ALL patient with MTX-induced clinical neurotoxicity, CSF-tau was above the detection limit of 2000 pg/ml. Almost one-third of the patients with hematological malignancies had elevated CSF-tau levels at diagnosis. Transient high levels of CSF-tau, reaching levels observed in other neurodegenerative disorders, were observed during induction chemotherapy for non-B-ALL, B-NHL and CNS+ AML. The clinical implications of both observations will be the subject of further study.
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Stefaan W Van Gool is a Postdoctoral Fellow of the Fund for Scientific Research, Flanders (Belgium) (FWO). We thank Fred Shapiro for editorial assistance.
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Van Gool, S., Van Kerschaver, E., Brock, P. et al. Disease- and treatment-related elevation of the neurodegenerative marker tau in children with hematological malignancies. Leukemia 14, 2076–2084 (2000). https://doi.org/10.1038/sj.leu.2401934
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DOI: https://doi.org/10.1038/sj.leu.2401934