Cerebrospinal Fluid Metabolomic Profiles Associated With Fatigue During Treatment for Pediatric Acute Lymphoblastic Leukemia.
Patient-reported symptoms
biomarkers
cancer-related fatigue
cerebrospinal fluid
metabolomics
pediatric acute lymphoblastic leukemia
Journal
Journal of pain and symptom management
ISSN: 1873-6513
Titre abrégé: J Pain Symptom Manage
Pays: United States
ID NLM: 8605836
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
02
06
2020
revised:
22
07
2020
accepted:
24
08
2020
pubmed:
6
9
2020
medline:
24
6
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
Cancer-related fatigue (CRF) is one of the most distressing and persistent symptoms reported during pediatric acute lymphoblastic leukemia (ALL) therapy; however, information on the pathways underlying CRF severity is limited. We conducted global metabolomics profiling of cerebrospinal fluid (CSF) samples to provide insight into the underlying mechanisms of CRF. Fatigue in pediatric ALL patients (2012-2017) was assessed during postinduction therapy approximately six months after diagnosis. Postinduction CSF was collected from 171 participants, comprising discovery (n = 86) and replication (n = 85) cohorts. We also conducted secondary validation using diagnostic CSF from 48 replication cohort participants. CSF metabolomic profiling was performed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS/MS. Kendall's rank correlation was used to evaluate associations between metabolite abundance and CRF. False discovery rate was used to account for multiple comparisons. Participants were 56% males and 59% Hispanic with a mean age at diagnosis of 8.5 years. A total of 274 CSF-derived metabolites were common to the discovery and replication cohorts. Eight metabolites were significantly associated with fatigue in the discovery cohort (P < 0.05), of which three were significant in the replication cohort, including false discovery rate-corrected associations with gamma-glutamylglutamine (P The metabolites identified in our assessment have been implicated in neurotransmitter transportation and glutathione recycling, suggesting that glutamatergic pathways or oxidative stress may contribute to ALL-associated CRF. This information could inform targeted therapies for reducing CRF in at-risk individuals.
Identifiants
pubmed: 32889041
pii: S0885-3924(20)30716-8
doi: 10.1016/j.jpainsymman.2020.08.030
pmc: PMC7914130
mid: NIHMS1625457
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
464-473Subventions
Organisme : NCI NIH HHS
ID : K07 CA218362
Pays : United States
Informations de copyright
Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
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