ONS Connections: Reliable biomarker for central nervous system tissue injury during pediatric leukemia treatment

PHOENIX—During the post-induction phase of treatment for childhood acute lymphoblastic leukemia (ALL), F2 isoprostanes significantly increase, allowing central nervous system (CNS) tissue injury to be monitored. This research was presented at the Oncology Nursing Society (ONS) Connections: Advancing Care Through Science conference.

In ALL, tissues of the CNS are prophylactically treated. This treatment, which is essential to cure ALL, most widely involves methotrexate. Among children younger than 15 years, ALL is the most common cancer, and survival rates now exceed 85%. Treating the CNS contributes to long-term disease-free survival, but it decreases academic abilities, particularly reading and math. Evidence is growing that methotrexate increases oxidative stress, which may injure the CNS. Since F2 isoprostanes are a well-established and validated measure of oxidative stress, they may serve as markers of CNS tissue injury during treatment for childhood ALL. Oxidative stress affects white matter and the hippocampus, which are important for such cognitive abilities as working memory, learning, and visual-spatial and visual-motor skills.

This longitudinal study measured F2 isoprostanes in cerebrospinal fluid in 33 children with ALL during four phases of their treatment: diagnosis; induction, meaning the first 28 days of systemic chemotherapy; post-induction, meaning approximately 6 months of aggressive chemotherapy targeted toward the CNS; and maintenance, meaning less aggressive systemic and CNS-targeted chemotherapy that lasted about 2.5 years. A total of 132 cerebrospinal fluid specimens were evaluated from the four phases of treatment.

The concentrations of F2 isoprostane in the cerebrospinal fluid ranged from 0.861 to 5.689 pg/ml, with a mean of 3.63 pg/ml. Levels of F2 isoprostane increased during the induction phase of therapy to a mean of 5.43 pg/ml. 

The greatest increase in F2 isoprostane levels occurred during the post-induction phase, when the mean concentration was 7.56 pg/ml. The post-induction phase increase was statistically significant, suggesting the F2 isoprostane levels can be a reliable biomarker to monitor CNS tissue injury during treatment for childhood leukemia.

“Personalized therapy for a highly curable disease such as childhood leukemia employing molecular and biochemical tools for clinical diagnosis will become reality as biomedical technology continues to envolve,” said the researchers. “Increased understanding of oxidative stress biomarkers related to childhood leukemia therapy may lead to knowledge of treatment-related symptom associations and their ultimate impact on childhood leukemia care,” they concluded.

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