title: 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 1,500 and 948 pg/ml, respectively. In one non-B-ALL patient with MTX-induced clinical neurotoxicity, CSF-tau was above the detection limit of 2,000 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.
authors.affiliation: Department of Pediatrics, Catholic University of Leuven, Belgium.
authors.forename: S W
authors.initials: SW
authors.lastname: Van Gool
authors.forename: E
authors.initials: E
authors.lastname: Van Kerschaver
authors.forename: P
authors.initials: P
authors.lastname: Brock
authors.forename: H
authors.initials: H
authors.lastname: Pottel
authors.forename: F
authors.initials: F
authors.lastname: Hulstaert
authors.forename: E
authors.initials: E
authors.lastname: Vanmechelen
authors.forename: A
authors.initials: A
authors.lastname: Uyttebroeck
authors.forename: A
authors.initials: A
authors.lastname: Van De Voorde
authors.forename: H
authors.initials: H
authors.lastname: Vanderstichele
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002648:Child; D019337:Hematologic Neoplasms / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D006801:Humans; D009483:Neuropsychological Tests; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D016875:tau Proteins