ABSTRACT
Acute lymphoblastic leukemia (ALL) is the most prevalent and curable cancer among children and adolescents less than 15 years of age in the United States. Essential for cure of childhood ALL is prophylactic treatment of the central nervous system (CNS), with methotrexate (MTX) being the most widely used drug in this treatment. While CNS treatment has contributed to long-term disease-free survival, resulting declines in academic abilities have been reported. There is growing evidence that CNS treatment with MTX increases oxidative stress, a potential mechanism of CNS injury. This article reports changes in oxidative stress, measured by the biomarker F2-isoprostane (F2-IsoP), in the cerebrospinal fluid (CSF) in 47 children with ALL during the first 18 months of treatment. The number of CSF samples ranged from 5 to 14 during postinduction and from 1 to 9 during continuation. Total doses of intrathecal MTX during postinduction were significantly correlated with the mean and highest concentrations of F2-IsoP during postinduction and the mean concentration of F2-IsoP during continuation. F2-IsoP concentrations during postinduction and continuation were higher in children who received more than six doses of intrathecal MTX. New therapies for a highly curable disease such as childhood leukemia have the potential to be individualized in the future, requiring reliable molecular and biochemical markers, such as oxidative stress indicators. Innovative use of biomarkers has the potential to increase our understanding of treatment-related toxicities and associated symptoms and to inform future therapeutic approaches for optimizing cure and quality of life among children with leukemia.
Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Biomarkers/cerebrospinal fluid , F2-Isoprostanes/cerebrospinal fluid , Methotrexate/adverse effects , Oxidative Stress/physiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Antimetabolites, Antineoplastic/administration & dosage , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Humans , Male , Methotrexate/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/cerebrospinal fluidABSTRACT
PURPOSE/OBJECTIVES: To explore the symptom trajectory during the first 16 months of childhood leukemia treatment and any associations with the oxidative stress pathway measured by cerebrospinal fluid (CSF) concentration of oxidized phosphatidylcholine (PC), the predominant glycerophospholipid in the brain and cell membranes. DESIGN: Prospective, longitudinal design. SETTING: Two cancer centers in the southwestern United States. SAMPLE: 36 children (aged 3-14 years) newly diagnosed with acute lymphoblastic leukemia. METHODS: Symptoms were measured using the Memorial Symptom Assessment Scale at six specific time points during treatment. Biochemical changes in oxidative stress were measured by oxidized PC in the CSF. MAIN RESEARCH VARIABLES: Childhood cancer symptoms, oxidized PC. FINDINGS: Significant differences were found in the number of symptoms experienced during the three phases of treatment. Symptom trajectory changes and influence of the oxidative stress pathway on symptom experiences were identified. CONCLUSIONS: Symptoms experienced during treatment for childhood leukemia are associated with increased oxidative stress. IMPLICATIONS FOR NURSING: Children with leukemia experience symptoms throughout treatment. Physiologic measures indicate the influence of oxidative stress on symptoms.