Children and adolescents with cancer report significantly more fatigue than their counterparts without cancer, and cancer-related fatigue (CRF) is “one of the most prevalent and distressing symptoms reported during childhood cancer therapy,” according to Austin L. Brown, PhD, and his colleagues.

Cerebrospinal fluid (CSF) profiles suggest three metabolites are significantly associated with CRF in children with acute lymphoblastic leukemia (ALL), according to a report published in the Journal of Pain and Symptom Management.

The researchers assessed the clinical and demographic characteristics of 171 pediatric ALL patients, who were divided into discovery (n = 86) and replication (n = 85) cohorts.

The entire population had a mean age at diagnosis of 8.48 years; was 56.1% male; and 85.4% had B-lineage ALL. A total of 63.7% received high- or very-high-risk treatment.

CSF samples were obtained and subjected to metabolomic analysis, according to Dr. Brown, an assistant professor at the Baylor College of Medicine, Houston, and colleagues.

The researchers analyzed postinduction CSF from the aforementioned 171 patients as well as diagnostic CSF from 48 patients in an additional replication cohort.

Significant metabolites

Analysis of postinduction CSF showed that three metabolites were significantly associated with fatigue in both the discovery and replication cohorts, comprising gamma-glutamylglutamine, dimethylglycine, and asparagine (P < .05).

In diagnostic CSF samples, the abundance of gamma-glutamylglutamine was significantly associated with fatigue (P =.0062).

The metabolites have been implicated in neurotransmitter transportation and glutathione recycling, suggesting glutamatergic pathways or oxidative stress may contribute to ALL-associated CRF, according to the researchers.

“Ultimately, this line of investigation may aid in the development of new prevention and treatment approaches informed by an improved understanding of the etiology and risk factors for cancer-related fatigue,” the researchers concluded.

The study was sponsored by the National Cancer Institute and several nonprofit organizations. The authors reported that they had no conflicts of interest.

SOURCE: Brown AL et al. J Pain Symptom Manage. 2020 Sep 1. doi: 10.1016/j.jpainsymman.2020.08.030.