title: Evaluation of Biomarkers of Oxidative Stress and Apoptosis in Patients With Severe Methotrexate Neurotoxicity: A Case Series.
abstract: Central nervous system (CNS) treatment is an essential part of acute lymphocytic leukemia (ALL) therapy, and the most common CNS treatment is intrathecal (IT) and high-dose intravenous (IV) methotrexate (MTX). Treatment with MTX may cause neurotoxicity, which is often accompanied by neurologic changes, delays in treatment, and prolonged hospital stays. This article reports clinical presentations of 3 patients with severe MTX toxicity as well as levels of oxidative stress and apoptosis biomarkers in cerebrospinal fluid (CSF). Oxidative stress was measured by oxidized phosphatidylcholine (PC), oxidized phosphatidylinositol (PI), and F2 isoprostanes; apoptosis was measured by caspase 3/7 activity. Most consistent biomarker changes in all 3 cases were increases in caspase 3/7 and F2 isoprostanes prior to acute toxicity while increases in oxidized phospholipids occurred slightly later. Progressive increases in F2 isoprostanes and caspase 3/7 activity prior to and/or during acute toxicity suggests MTX induces oxidative stress and an associated increase in apoptosis. These findings support the role of oxidative stress in MTX-related neurotoxicity.
authors: Baylor College of Medicine Houston, TX, USA oataylor@txch.org.
authors: Olga A
authors: OA
authors: Taylor
authors: Duke School of Nursing, Durham, NC, USA.
authors: Marilyn J
authors: MJ
authors: Hockenberry
authors: Baylor College of Medicine Houston, TX, USA.
authors: Kathy
authors: K
authors: McCarthy
authors: University of Arizona College of Nursing, Tucson, AZ, USA.
authors: Patricia
authors: P
authors: Gundy
authors: Southern Arizona VA Health Care System, Tucson, AZ, USA.
authors: David
authors: D
authors: Montgomery
authors: University of Arizona College of Nursing, Tucson, AZ, USA.
authors: Adam
authors: A
authors: Ross
authors: Baylor College of Medicine Houston, TX, USA.
authors: Michael E
authors: ME
authors: Scheurer
authors: University of Arizona College of Nursing, Tucson, AZ, USA.
authors: Ida M
authors: IM
authors: Moore
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000633:toxicity*; D017209:Apoptosis; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000633:toxicity*; D018384:Oxidative Stress; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000451:nursing; D012720:Severity of Illness Index
chemical_list: D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D008727:Methotrexate
keywords: leukemia; methotrexate; neurotoxicity; oxidative stress
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