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Neurochemical markers of brain damage in cerebrospinal fluid during induction treatment of acute lymphoblastic leukemia in children
Author(s) -
Österlundh Gustaf,
Kjellmer Ingemar,
Lannering Birgitta,
Rosengren Lars,
Nilsson Ulf A.,
Márky Ildikó
Publication year - 2008
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21378
Subject(s) - medicine , cerebrospinal fluid , enolase , glial fibrillary acidic protein , methotrexate , lymphoblastic leukemia , gastroenterology , neurochemical , intrathecal , central nervous system , neurotoxicity , brain damage , leukemia , anesthesia , toxicity , immunohistochemistry
Background Central nervous system (CNS) irradiation has been replaced by systemic high‐dose methotrexate (MTX) and intrathecal MTX in acute lymphoblastic leukemia treatment due to the risk of late effects.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. Procedure 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) µg/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. Pediatr Blood Cancer 2008;50:793–798. © 2007 Wiley‐Liss, Inc.