title: Impact of chemotherapy for childhood leukemia on brain morphology and function.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Genschaft
authors.forename: Thomas
authors.initials: T
authors.lastname: Huebner
authors.forename: Franziska
authors.initials: F
authors.lastname: Plessow
authors.forename: Vasiliki N
authors.initials: VN
authors.lastname: Ikonomidou
authors.forename: Nasreddin
authors.initials: N
authors.lastname: Abolmaali
authors.forename: Franziska
authors.initials: F
authors.lastname: Krone
authors.forename: Andre
authors.initials: A
authors.lastname: Hoffmann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Holfeld
authors.forename: Peter
authors.initials: P
authors.lastname: Vorwerk
authors.forename: Christof
authors.initials: C
authors.lastname: Kramm
authors.forename: Bernd
authors.initials: B
authors.lastname: Gruhn
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Koustenis
authors.forename: Pablo
authors.initials: P
authors.lastname: Hernaiz-Driever
authors.forename: Rakesh
authors.initials: R
authors.lastname: Mandal
authors.forename: Meinolf
authors.initials: M
authors.lastname: Suttorp
authors.forename: Thomas
authors.initials: T
authors.lastname: Hummel
authors.forename: Chrysanthy
authors.initials: C
authors.lastname: Ikonomidou
authors.forename: Clemens
authors.initials: C
authors.lastname: Kirschbaum
authors.forename: Michael N
authors.initials: MN
authors.lastname: Smolka
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D002648:Child; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D059906:Neuroimaging; D009483:Neuropsychological Tests; D009929:Organ Size / Q000187:drug effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012903:Smell / Q000187:drug effects; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents