monodehydroascorbate and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Central nervous system (CNS) irradiation has been replaced by systemic high-dose methotrexate (MTX) and intrathecal MTX in acute lymphoblastic leukemia treatment due to the risk of late effects.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.. 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.. 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.. 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.

Topics: Adolescent; Antimetabolites, Antineoplastic; Biomarkers; Brain; Brain Damage, Chronic; Brain Injuries; Child; Child, Preschool; Dehydroascorbic Acid; Female; Glial Fibrillary Acidic Protein; Humans; Infant; Male; Methotrexate; Neurofilament Proteins; Phosphopyruvate Hydratase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radioimmunoassay

Ascorbyl radical (ASR) in human cerebrospinal fluid (CSF) of various patients using electron paramagnetic resonance (EPR) at ambient temperature was investigated. Also, effect of chemotherapy on ASR as well as ascorbate (ASA) in CSF and serum of acute lymphoblastic leukemia (ALL) was studied. EPR spectra of various CSF samples showed a characteristic doublet, which was attributed to ASR. ASR in CSF and serum was directly measured without any chemical modification. ASA and ASR concentration in CSF were approximately two times higher than those in serum. ASA and ASR concentrations in CSF and serum were statistically analyzed. The analyses showed that ASR and ASA in CSF and serum had good correlation for patients undergoing chemotherapy but not for patients after the therapy. The correlation for ASR and ASA suggests that ascorbate may play an important role during chemotherapy. In addition, dynamic aspects of ASA and ASR in CSF and serum are discussed.

Topics: Adolescent; Adult; Antineoplastic Agents; Ascorbic Acid; Child; Child, Preschool; Dehydroascorbic Acid; Electron Spin Resonance Spectroscopy; Female; Humans; Male; Middle Aged; Models, Chemical; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Temperature