An observational MRI study of methotrexate-treated children with acute lymphoblastic leukemia in remission and subtle cognitive decline

Abstract

Background: For children diagnosed with acute lymphoblastic leukemia (ALL), methotrexate (MTX) treatment carries the risk of leukoencephalopathy and other treatment-related brain damage. However, earlier and more sensitive evaluation is needed to elucidate the specific effects of MTX treatment in this group. This study aimed to evaluate changes in brain metabolites, diffusion and anisotropy features, and cognitive performance in children with ALL after MTX treatment. Methods:In this observational study conducted from December 2013 to December 2015, 30 children with ALL and 30 healthy children were recruited and evaluated using baseline magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and neurocognitive tests. After MTX treatment and ALL remission, the children with ALL underwent MR examination and neurocognitive tests again. Quantitative alterations of MR and cognitive test results from the baseline data were calculated.Results: At baseline, the ALL group (age 6.9±3.3 years; 14 boys) and the healthy controls (age 6.0±3.1 years, 14 boys) had comparable neurocognitive performance and MR results. After MTX treatment, 6.7%(2/30) of children with ALL showed abnormalities on diffusion-and T1-and T2-weighted images. The N-acetylaspartate/creatine and N-acetylaspartate/choline values of children with ALL decreased, whereas their choline/creatine values increased significantly. The fractional anisotropy (FA) values decreased in the frontal lobe (P=0.03) and the genu of the corpus callosum (P=0.01). The FA values in the genu of the internal capsule (P=0.08), the occipital lobe (P=0.20) and the splenium of the corpus callosum (P=0.30) did not change from baseline. The apparent diffusion coefficient (ADC) values decreased in the frontal lobe (P=0.03).The ADC values in the genu of the corpus callosum (P=0.11), the genu of the internal capsule (P=0.93), and the occipital lobe (P=0.65) did not change from baseline. Due to the presence of outliers and the small sample, the ADC values in the splenium of the corpus callosum were discarded. Neurocognitive performance decreased slightly after MTX treatment, with noticeable declines in working memory and processing speed.Changes in FA values were positively correlated with the reduction in the N-acetylaspartate/creatine ratio at the genu of the corpus callosum of children with ALL aged above 6 years.Conclusions: MTX treatment causes subtle cognitive decline in children with ALL in remission and dramatically affects their brain metabolites, but changes in white matter diffusion features are limited to the ^ ORCID: 0000-0002-1356-3705. Methods Methods and materialsThis study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of Shenzhen Children's Hospital, and informed consent for each of the patients was acquired from their parents or legal guardians. frontal lobe and corpus callosum.

Cumulative Dosage of Intrathecal Chemotherapy Agents Predicts White Matter Integrity in Long-Term Survivors of Acute Lymphoblastic Leukemia: A PETALE Study

“…FA is a more specific measure of the directionality and coherence of water diffusion along WM tracts, which reflects the spatial organization and alignment of WM fibers [ 77 ]. FA has been extensively investigated in ALL survivors, revealing decreased FA values in various regions, including the frontal lobe, the frontostriatal tracts, and the CC [ 24 , 78 ]. In contrast, very few studies have investigated MTR to detect WM alterations in ALL survivors.…”

“…According to their performance at the DIVERGT screening procedure [5,26], a sample of 35 ALL survivors (age range ), aiming to represent all spectrum of cognitive performance found in the initial cohort, was selected, tested using anatomical MRI studies and included in this study. For comparison purposes, 21 age-and education-level-matched healthy controls (age range (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)), representative with respect to sex, with no history of neurological, psychological, or cancer disorders, were recruited within SJUHC Research Center and within social networks. The complete recruitment procedure is detailed elsewhere [27].…”

“…The integrity of the interhemispheric connection pathways is essential for the proper functioning of the brain. Several studies observed microstructural changes in the CC following oncological treatments based on systemic chemotherapy [ 20 , 21 , 22 , 23 , 24 ]. However, very few studies have focused on the MTR.…”