Impact of chemotherapy for childhood leukemia on brain morphology and function

• Published in: PloS one 2013-11, Vol.8 (11), p.e78599
• Main Authors: Genschaft, Marina, Huebner, Thomas, Plessow, Franziska, Ikonomidou, Vasiliki N, Abolmaali, Nasreddin, Krone, Franziska, Hoffmann, Andre, Holfeld, Elisabeth, Vorwerk, Peter, Kramm, Christof, Gruhn, Bernd, Koustenis, Elisabeth, Hernaiz-Driever, Pablo, Mandal, Rakesh, Suttorp, Meinolf, Hummel, Thomas, Ikonomidou, Chrysanthy, Kirschbaum, Clemens, Smolka, Michael N
• Format: Article
• Language: English
• Subjects: Adolescent; Adolescents; Age; Amygdala; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Bioengineering; Brain; Brain - drug effects; Brain - pathology; Brain - physiopathology; Brain cancer; Bulbs; Cancer; Cancer therapies; Central nervous system; Chemotherapy; Child; Childhood; Children; Cognition; Cognitive ability; Cortex (parietal); Data analysis; Data processing; Diffusion Tensor Imaging; Disease control; Engineering schools; Female; Hematology; Hippocampus; Humans; Image processing; Image segmentation; Information management; Intelligence; Intravenous administration; Leukemia; Lymphatic leukemia; Magnetic resonance; Magnetic resonance imaging; Male; Medical imaging; Medical research; Memory - drug effects; Morphology; Morphometry; Neocortex; Neurogenesis; Neurogenesis - drug effects; Neuroimaging; Neuropsychological Tests; Nucleus accumbens; Olfaction; Olfactory bulb; Organ Size - drug effects; Pediatrics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - physiopathology; Radiation; Segmentation; Smell - drug effects; Substantia alba; Substantia grisea; Thalamus; Toxicity; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078599

Using multidisciplinary treatment modalities the majority of children with cancer can be cured but we are increasingly faced with therapy-related toxicities. We studied brain morphology and neurocognitive functions in adolescent and young adult survivors of childhood acute, low and standard risk lymphoblastic leukemia (ALL), which was successfully treated with chemotherapy. We expected that intravenous and intrathecal chemotherapy administered in childhood will affect grey matter structures, including hippocampus and olfactory bulbs, areas where postnatal neurogenesis is ongoing. We examined 27 ALL-survivors and 27 age-matched healthy controls, ages 15-22 years. ALL-survivors developed disease prior to their 11th birthday without central nervous system involvement, were treated with intrathecal and systemic chemotherapy and received no radiation. Volumes of grey, white matter and olfactory bulbs were measured on T1 and T2 magnetic resonance images manually, using FIRST (FMRIB's integrated Registration and Segmentation Tool) and voxel-based morphometry (VBM). Memory, executive functions, attention, intelligence and olfaction were assessed. Mean volumes of left hippocampus, amygdala, thalamus and nucleus accumbens were smaller in the ALL group. VBM analysis revealed significantly smaller volumes of the left calcarine gyrus, both lingual gyri and the left precuneus. DTI data analysis provided no evidence for white matter pathology. Lower scores in hippocampus-dependent memory were measured in ALL-subjects, while lower figural memory correlated with smaller hippocampal volumes. Findings demonstrate that childhood ALL, treated with chemotherapy, is associated with smaller grey matter volumes of neocortical and subcortical grey matter and lower hippocampal memory performance in adolescence and adulthood.