Neurochemical markers of brain damage in cerebrospinal fluid during induction treatment of acute lymphoblastic leukemia in children.
BACKGROUND
Central nervous system (CNS) irradiation has been replaced by systemic high-dose methotrexate (MTX) and intrathecal MTX in acute lymphoblastic leukemia treatment due to the risk of late effects. However, treatment without CNS irradiation might also cause brain damage.


METHODS
Cerebrospinal fluid (CSF) was analyzed in 121 patients in an attempt to detect CNS injury. Seventy-three samples were analyzed for neuron-specific enolase (NSE), 108 for glial fibrillary acidic protein (GFAp), 110 for neurofilament protein light chain (NFp), and 70 for ascorbyl radical (AsR). Samples were taken at day 0, 8, 15, and 29 during induction treatment, including intrathecal MTX. Levels at days 8, 15, and 29 were compared with the levels before treatment.


RESULTS
NSE levels were 9.0 (+/-3.5) microg/L (mean (+/-SD)) at day 0, 15.0 (+/-5.3) at day 8 (P < 0.001), 13.6 (+/-4.7) at day 15 (P < 0.001) and 11.1 (+/-4.3) at day 29 (P < 0.001). GFAp were 177 (+/-98) ng/L at day 0, 206 (+/-101) at day 8 (P < 0.001), 200 (+/-106) at day 15 (n.s.) and 228 (+/-137) at day 29 (P < 0.001). NFp were below the detection limit 125 ng/L at day 0 in all 110 CSF samples analyzed, and increased significantly above the detection limit in 6/77 samples at day 8, in 11/84 at day 15 and in 22/91 at day 29. The AsR content did not change significantly.


CONCLUSIONS
Levels of NSE, GFAp, and NFp increased in CSF, which can be interpreted as early signs of brain damage. AsR levels do not show any convincing signs of oxidative stress.
Osterlundh
Gustaf
G
Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. gustaf.osterlundh@pediat.gu.se
Kjellmer
Ingemar
I
Lannering
Birgitta
B
Rosengren
Lars
L
Nilsson
Ulf A
UA
Márky
Ildikó
I
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000187:drug effects*; D001925:Brain Damage, Chronic / Q000134:cerebrospinal fluid / Q000139:chemically induced; D001930:Brain Injuries; D002648:Child; D002675:Child, Preschool; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid*; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011863:Radioimmunoassay
D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; C044882:neurofilament protein L; C000820:semidehydroascorbic acid; D010751:Phosphopyruvate Hydratase; D003683:Dehydroascorbic Acid; D008727:Methotrexate