title: Chemotherapy-related changes in central nervous system phospholipids and neurocognitive function in childhood acute lymphoblastic leukemia.
abstract: Long-term survivors of childhood leukemia are at risk for neurocognitive impairment, although the neurophysiological basis is not well understood. The purpose of this study was to explore associations between changes in cerebrospinal fluid (CSF) phospholipids and neurocognitive function in children undergoing chemotherapy for acute lymphoblastic leukemia. Seventy-six children were followed prospectively from diagnosis. CSF samples were collected during scheduled lumbar punctures and phospholipids were extracted. Neurocognitive evaluations were conducted annually beginning shortly after diagnosis. Concentrations of sphingomyelin (SM) increased following induction (p = 0.03) and consolidation (p = 0.04), while lysophosphatidylcholine (LPC) increased following induction (p = 0.003). Multivariable analyses demonstrated associations between post-induction SM and motor speed at 1 year (p < 0.001), 2 years (p = 0.001) and 3 years (p = 0.02) following diagnosis. Post-induction LPC was associated with verbal working memory (p = 0.007). Results indicate that early changes in phospholipids are related to neurocognitive decline and suggest a chemotherapy impact on white matter integrity.
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA. kevin. krull@stjude.org
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Krull
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Hockenberry
authors.forename: Petra
authors.initials: P
authors.lastname: Miketova
authors.forename: Marissa
authors.initials: M
authors.lastname: Carey
authors.forename: Ida M
authors.initials: IM
authors.lastname: Moore
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D017063:Outcome Assessment, Health Care; D010713:Phosphatidylcholines / Q000134:cerebrospinal fluid; D010714:Phosphatidylethanolamines / Q000134:cerebrospinal fluid; D010743:Phospholipids / Q000134:cerebrospinal fluid*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000523:psychology; D013109:Sphingomyelins / Q000134:cerebrospinal fluid; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D013109:Sphingomyelins; C483858:phosphatidylethanolamine; D008727:Methotrexate