A quantitative MR imaging assessment of leukoencephalopathy in children treated for acute lymphoblastic leukemia without irradiation.
OBJECTIVE
Intravenous methotrexate (IV-MTX), an effective treatment for acute lymphoblastic leukemia (ALL), has a significant toxic effect on the central nervous system, with leukoencephalopathy (LE) being the most common form. The purpose of this study was to use objective quantitative MR imaging to prospectively assess the temporal evolution of LE extent and intensity.


METHODS
Forty-five children (low-risk, 10 mol/L/12F; mean age, 5.0 years at diagnosis; standard/high-risk, 11 mol/L/12F; mean age, 9.2 years at diagnosis) treated for ALL on a single institutional protocol were evaluated longitudinally to assess the extent of LE (proportion of white matter impacted) through tissue segmentation and the relative intensity of LE through relative elevations in T1 and T2 relaxation rates. One-sided Wilcoxon-Mann-Whitney tests were used to assess differences in quantitative measures at 4 different points in therapy both within and between risk arms.


RESULTS
The proportion of white matter affected in both patient groups increased significantly with additional courses of IV-MTX, whereas the intensity of LE also increased steadily; however, both the intensity and extent of LE declined significantly approximately 1.5 years after completion of IV-MTX. Increases in the T1 and T2 relaxation rates above normal-appearing white matter were significantly correlated with each other and were dependent on the proportion of white matter affected.


CONCLUSIONS
Higher doses and more courses of IV-MTX were associated with increased intensity and extent of LE. There was a significant reduction in both the intensity and extent of LE after completion of therapy. The impact 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, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Glass
John O
JO
Helton
Kathleen J
KJ
Langston
James W
JW
Li
Chin-Shang
CS
Pui
Ching-Hon
CH
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001927:Brain Diseases / Q000139:chemically induced* / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D008279:Magnetic Resonance Imaging; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate