Neurotoxicity marker profiles in the CSF are not age-dependent but show variation in children treated for acute lymphoblastic leukemia.
BACKGROUND
In children treated for hematological malignancies, a transient elevation of the neurodegenerative marker Tau was found in the cerebrospinal fluid (CSF). In the first part of this study, CSF-Tau, CSF-Phospho-Tau, and CSF-Neuromodulin (CSF-NM) were measured in a heterogeneous group of patients presenting in the pediatric oncology department. In the second part, the neurodegenerative markers were analyzed in a group of children with non-B-cell acute lymphoblastic leukemia (nB-ALL) treated according to EORTC protocols 58881 and 58951.


METHODS
CSF was collected from lumbar punctures at diagnosis only in the first group, and at diagnosis and during treatment in the second group. CSF-proteins were measured with ELISA.


RESULTS
There was no age variation in any of the markers at diagnosis in the first group of children. After prephase induction therapy with one intrathecal (IT) injection of methotrexate (MTX) and 7 days systemic corticosteroids, an increase in CSF-Tau was observed, and accompanied with increase of both CSF-P-Tau and CSF-NM. While CSF-Tau remained high during induction treatment, CSF-P-Tau, and CSF-NM decreased.


CONCLUSIONS
Neurodegenerative markers do not vary with age. The different protein profiles suggest that the neurotoxicity from the prephase, which results in an increase of CSF-Tau, CSF-P-Tau, and CSF-NM, may have a different mechanism to the neurotoxicity induced later during induction treatment, when only CSF-Tau remains high.
Van Gool
Stefaan W
SW
Department of Pediatrics, Catholic University of Leuven, Leuven, Belgium. stefaan.vangool@uz.kuleuven.ac.be
De Meyer
Geert
G
Van de Voorde
André
A
Vanmechelen
Eugeen
E
Vanderstichele
Hugo
H
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000134:cerebrospinal fluid / Q000633:toxicity; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000134:cerebrospinal fluid* / Q000633:toxicity*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D016014:Linear Models; D008297:Male; D008727:Methotrexate / Q000134:cerebrospinal fluid / Q000633:toxicity; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D016875:tau Proteins; D008727:Methotrexate