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Clinical Laboratory Correlates in AML

Disease- and treatment-related elevation of the neurodegenerative marker tau in children with hematological malignancies

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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Acknowledgements

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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