title: Increase in oxidative stress as measured by cerebrospinal fluid lipid peroxidation during treatment for childhood acute lymphoblastic leukemia.
abstract: Five-year survival from childhood acute lymphoblastic leukemia (ALL) approaches 90%, but 40% of survivors experience central nervous system (CNS) treatment-related cognitive problems. Despite considerable evidence for cognitive problems, less is known about mechanisms of neurological injury. Our purpose was to investigate oxidative stress, measured by lipid peroxidation, as a mechanism of CNS treatment-related neurological injury. The sample included 55 children (mean age at diagnosis=6.84 y, SD=3.40) who received intrathecal and intravenous chemotherapy for CNS-directed treatment according to Children's Oncology Group protocols. Glycerophospholipids were extracted from cerebrospinal fluid samples obtained at diagnosis and during intrathecal chemotherapy administration. Unoxidized and oxidized phosphatidylcholine (PC) and phosphatidylinositol (PI) were measured by normal phase high-performance liquid chromatography with diode array detection, and analyzed with a general linear model for repeated measures analysis of variance. Compared with the diagnostic cerebrospinal fluid sample, unoxidized and oxidized PC and PI increased significantly across treatment phases. Amount of intravenous methotrexate received was significantly correlated with oxidized PI, and age at time of ALL diagnosis was significantly associated with oxidized PC. These findings support our hypothesis that oxidative stress is a mechanism of neurological injury associated with CNS-directed treatment for ALL.
authors.affiliation: *University of Arizona College of Nursing †University of Arizona College of Nursing and Research Service, Southern Arizona VA Health Care System, Tucson, AZ ‡Baylor College of Medicine, Houston, TX §Duke School of Nursing, Durham, NC.
authors.forename: Ida M
authors.initials: IM
authors.lastname: Ki Moore
authors.forename: Patricia
authors.initials: P
authors.lastname: Gundy
authors.forename: Alice
authors.initials: A
authors.lastname: Pasvogel
authors.forename: David W
authors.initials: DW
authors.lastname: Montgomery
authors.forename: Olga A
authors.initials: OA
authors.lastname: Taylor
authors.forename: Kari M
authors.initials: KM
authors.lastname: Koerner
authors.forename: Kathy
authors.initials: K
authors.lastname: McCarthy
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Hockenberry
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001927:Brain Diseases / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010713:Phosphatidylcholines / Q000032:analysis; D010716:Phosphatidylinositols / Q000032:analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy; D011379:Prognosis
chemical_list: D010713:Phosphatidylcholines; D010716:Phosphatidylinositols