The Longitudinal Parallel Process Analysis of Biomarkers of Oxidative Stress, Symptom Clusters, and Cognitive
Mary C Hooke1,2, Daniel Hatch3, Marilyn J Hockenberry2,4
1University of Minnesota, Minneapolis, MN, USA.
Insights
Children undergoing acute lymphoblastic leukemia (ALL) treatment with lower oxidative stress experienced fewer symptoms and better cognition. Higher glutathione biomarkers, indicating less oxidative stress, correlated with improved outcomes in pediatric leukemia patients.
Area of Science:
- Pediatric Oncology
- Neuro-Oncology
- Translational Medicine
Background:
- Children with acute lymphoblastic leukemia (ALL) often experience a cluster of symptoms including fatigue, sleep disturbance, pain, nausea, and depression.
- Central nervous system-directed therapies for ALL increase the risk of cognitive impairments in children.
- Cancer treatments can elevate oxidative stress, potentially contributing to these treatment-related symptoms and cognitive deficits.
Purpose of the Study:
- To investigate the longitudinal relationships between cerebrospinal fluid oxidative stress biomarkers, the Childhood Cancer Symptom Cluster-Leukemia (CCSC-L), and cognitive function in children during the first year of ALL treatment.
- To explore how changes in glutathione (GSH) biomarkers over time influence symptom clusters and cognition.
Main Methods:
- GSH biomarkers, a measure of oxidative stress, were analyzed in cerebrospinal fluid from 132 children (aged 3-18) with ALL at four time points during the first year of treatment.
- Symptom severity (CCSC-L) and cognitive function were assessed longitudinally using self-reports (for participants aged 7+) and parent reports.
- A longitudinal parallel-process model analyzed the impact of initial GSH levels and their changes on CCSC-L and cognition.
Main Results:
- GSH biomarkers increased over time, signifying a decrease in oxidative stress during the treatment year.
- Higher initial GSH biomarker levels (indicating less oxidative stress) were associated with lower CCSC-L severity and better cognitive function at baseline.
- Cognitive function showed improvement over the four measurement time points in relation to GSH levels.
Conclusions:
- Reduced oxidative stress, as indicated by higher GSH biomarkers, is linked to a less severe symptom cluster and better cognitive function in children undergoing ALL treatment.
- Monitoring oxidative stress may provide a basis for developing future interventions to mitigate symptom distress and cognitive impairments in pediatric leukemia patients.
Abstract:
Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system-directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster-Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar punctures. GSH biomarkers, symptoms, and cognitive function of 132 children aged 3 to 18 years were evaluated at four time points during the first year of leukemia treatment. Participants, 7 years and older, completed self-report measures, and parents reported for younger children. Cognitive function measurements for all participants were completed by parents. A longitudinal parallel-process model was used to explore the influence of the initial measurement and the subsequent change over four time points of the GSH biomarkers on the CCSC-L and cognition. Results: GSH biomarkers increased over the four time points indicating decreasing oxidative stress. When GSH biomarkers were higher (less oxidative stress) at the initial measurement, the CCSC-L severity was lower, cognition was better, and cognition improved over the four measurements. Screening children for high levels of oxidative stress would be a foundation for future intervention studies to address symptom distress and cognitive impairments.
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