Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate.
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.
Reddick
Wilburn E
WE
Division of Translational Imaging Research, Department of Radiological Sciences, St. Jude Children's Research Hospital, 332 N. Lauderdale Street, Memphis, TN 38105-2794, USA.
Glass
John O
JO
Helton
Kathleen J
KJ
Langston
James W
JW
Xiong
Xiaoping
X
Wu
Shengjie
S
Pui
Ching-Hon
CH
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
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate