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To look for the presence and age-dependence of late structural alterations of otherwise normal-appearing cerebral gray and white matter after radiation and chemotherapy in adult survivors of acute lymphoblastic leukemia (ALL) during childhood.In a group of 13 adult survivors 17–37 years old, who had been treated by total brain radiation (18–24 Gy) and chemotherapy 16–28 years ago, prospective MR examinations including diffusion tensor imaging (DTI) were performed. Evaluation included volumetry, calculation of mean diffusivity (MD) and fractional anisotropy (FA), and comparison of results to an age-matched control group.DTI showed significantly reduced FA values in the temporal lobes (difference of 0.069 units, P < 0.001), hippocampi (difference of 0.033 units, P < 0.001), and thalami (difference of 0.046 units, P = 0.001), which were accompanied by significant white matter volume loss (difference of 92 cm3, P < 0.001). Significant elevations of MD were limited to the temporal white matter (difference of 42 × 10−6 mm2/s, P = 0.005). Global and frontal white matter MD correlated negatively to increasing age of the survivors (P < 0.01).With regard to structural white matter alterations, adult long-term survivors of childhood ALL, who had received total brain radiation and chemotherapy, apparently show the same overall age dependence as controls. Follow-up studies are needed for confirmation. J. Magn. Reson. Imaging 2008;27:1250–1255. © 2008 Wiley-Liss, Inc.