title: Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate.
abstract: OBJECTIVE
  An effective treatment for acute lymphoblastic leukemia (ALL), intravenous (IV) methotrexate (MTX) has a notable toxic effect on the CNS, with leukoencephalopathy (LE) being the most common form. The purpose of this study was to use objective quantitative MR imaging to prospectively assess potential risk factors on the temporal evolution of LE in patients treated for ALL.
  
  
  METHODS
  We evaluated the longitudinal prevalence of LE in 45 children treated for ALL in a single institutional protocol including seven courses of IV MTX and no cranial irradiation. Differences in signal intensity on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images between hyperintense regions and normal-appearing genu were used to quantitatively detect LE. Cox proportional regression was used to estimate the effect of covariates (e.g., sex, MTX dose, age at diagnosis) on the prevalence of LE. After influential factors were identified, a generalized linear model was determined to predict the probability of LE in new patients. The model was necessary to facilitate statistical testing between examinations.
  
  
  RESULTS
  Increasing exposure, which corresponding to more courses and higher doses of IV MTX, influenced the prevalence of LE. The prevalence of LE was significant reduced approximately 1.5 years after the completion of IV MTX.
  
  
  CONCLUSIONS
  Higher doses and more courses of IV MTX placed patients at a higher risk for LE; many of the changes resolved after the completion of therapy. The effect of these changes on neurocognitive functioning and quality of life in survivors remains to be determined.
authors.affiliation: Division of Translational Imaging Research, Department of Radiological Sciences, St. Jude Children's Research Hospital, 332 N. Lauderdale Street, Memphis, TN 38105-2794, USA.
authors.forename: Wilburn E
authors.initials: WE
authors.lastname: Reddick
authors.forename: John O
authors.initials: JO
authors.lastname: Glass
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Helton
authors.forename: James W
authors.initials: JW
authors.lastname: Langston
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xiong
authors.forename: Shengjie
authors.initials: S
authors.lastname: Wu
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001927:Brain Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate