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Cited by 75Cancer-related cognitive impairment studiesAcute Lymphoblastic Leukemia researchChildhood Cancer Survivors' Quality of Life

Impact of Chemotherapy for Childhood Leukemia on Brain Morphology and Function

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Genschaft, Marina, Huebner, Thomas, Plessow, Franziska, Ikonomidou, Vasiliki N., Abolmaali, Nasreddin, Krone, Franziska, Hoffmann, Andre, Holfeld, Elisabeth +11 more·2013·PLoS ONE
DOI 10.1371/journal.pone.0078599PMC PMC3827075
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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. INTERPRETATION: 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.

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  • Detailed characterization of region-specific changes associated with chemotherapy treatment remains scant.

    “Thirdly, while global changes in tissue volumes have been reported (Krull et al., 2016; Reddick et al., 2014; Tamnes et al., 2015), detailed characterization of region‐specific changes associated with chemotherapy treatment remains scant (Genschaft et al., 2013).”

    From Brain structure, working memory and response inhibition in childhood leukemia survivors (2017) · cites this paper as Genschaft et al., 2013

    The Introduction says the authors examined selected brain regions, and the Results (Structural Brain Imaging; page unavailable) report region-specific volume differences. Neither passage assesses whether detailed characterization of chemotherapy-associated regional changes was scarce in the literature. The paper's own regional analysis does not, by itself, settle that broader claim. (LLM, conf=0.70)

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Authors
Genschaft, M., Huebner, T., Plessow, F., Ikonomidou, V. N., Abolmaali, N., Krone, F., Hoffmann, A., Holfeld, E., Vorwerk, P., Kramm, C., Gruhn, B., Koustenis, E., Hernaiz-Driever, P., Mandal, R., Suttorp, M., Hummel, T., Ikonomidou, C., Kirschbaum, C., & Smolka, M. N.
Affiliations
  • University Hospital Carl Gustav Carus (DE)
  • Neuroimaging Center (DE)
  • Technische Universität Dresden (DE)
  • George Mason University (US)
  • Klinikum Chemnitz (DE)
  • Medizinische Universität Lausitz - Carl Thiem (DE)
  • Otto-von-Guericke-Universität Magdeburg (DE)
  • University Hospital in Halle (DE)
  • Friedrich Schiller University Jena (DE)
  • Charité – Universitätsmedizin Berlin (DE)
  • University of Wisconsin–Madison (US)
Corresponding author
Ikonomidou, Vasiliki N.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-11-12
Volume
8
Issue
11
Pages
e78599
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0078599
PMC
PMC3827075
OpenAlex
W1988693466
Cited by
75
References
39
Citations by year
2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 10 · 2020: 11 · 2019: 8 · 2018: 9 · 2017: 5 · 2016: 8 · 2015: 5 · 2014: 1
FWCI
3.79
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Childhood Cancer Survivors' Quality of Life
Keywords
childhood acute lymphoblastic leukemia, chemotherapy-induced neurotoxicity, brain structure, hippocampal volume, olfactory bulb, gray matter volume, neurocognitive function, memory, executive function, olfaction, intrathecal chemotherapy, adolescent and young adult cancer survivors, voxel-based morphometry, diffusion tensor imaging
MeSH terms
Adolescent, Antineoplastic Agents, Brain, Child, Female, Humans, Male, Memory, Neuropsychological Tests, Organ Size, Smell, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neurogenesis, Young Adult, Diffusion Tensor Imaging, Neuroimaging

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