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The focus on a cure for childhood leukemia over the last three decades has resulted in survival rates of more than 80%. However, efforts to manage leukemia-treatment symptoms have not kept pace with new therapies. Symptom toxicity during treatment can result in complications, treatment delays, and therapy dose reductions. Compromise in therapy can negatively influence the quality of life and, even more notably, jeopardize chances for long-term survival. This study examined biologic mechanisms that influence fatigue caused by increased reactive oxidative species (ROS) or actual failure of the antioxidant defense system due to genetic variation by investigating reactive nitrosative species, a “downstream” consequence of ROS. The specific aims of this study were to characterize the trajectory of nitrosative stress during acute lymphoblastic leukemia treatment and evaluate the influence of nitrosative stress on fatigue. A repeated measures design was used to evaluate the fatigue experienced by 186 children and adolescents, 3–18 years of age, with a diagnosis of leukemia during the most intense phase of treatment. An established biomarker of nitrosative stress, protein 3-nitrotyrosine (3NT) residues in the cerebral spinal fluid, was evaluated at diagnosis, postinduction, and consolidation phases of treatment. Higher fatigue was associated with higher 3NT levels at the beginning of treatment. Two distinct groups of children experienced either consistently high or consistently low 3NT levels across the treatment trajectory, from diagnosis to 12 months postinduction. Findings from this study support continued exploration into the phenotypic biochemical mechanisms that influence a reactive response to childhood cancer treatment. [ABSTRACT FROM AUTHOR]

Aggressive central nervous system (CNS)-directed treatment for acute lymphoblastic leukemia (ALL), the most prevalent cancer among children and adolescents, prevents metastasis of leukemia cells into the brain. Up to 60% of survivors experience cognitive problems, but knowledge about risk factors for and mechanisms of neurologic injury is lacking. Objectives of the present study were to (1) quantify changes in oxidant defense and apoptosis over the course of ALL therapy and (2) elucidate risk factors for long-term cognitive problems. The sample included 71 children with ALL. Cerebrospinal fluid (CSF) samples were collected at diagnosis and during intrathecal chemotherapy administration. Oxidant defense was measured by reduced glutathione (GSH), oxidized glutathione (GSSG), and the ratio of GSH:GSSG. Apoptosis was measured by activity of several cysteine-dependent aspartate-specific protease (abbreviated as caspase) enzymes that initiate (caspases 8 and 9) or execute (caspases 3/7) apoptosis. Cognitive abilities were assessed by standardized measures of short-term memory, visual-motor integration, and attention 3 years after ALL diagnosis. GSH and GSSG concentration increased significantly during ALL therapy, and a low GSH:GSSG ratio was indicative of an oxidized extracellular environment. Caspase enzyme activity increased significantly, and caspases 3/7 activity was significantly and negatively associated with performance on measures of cognitive abilities. Younger age at time of ALL diagnosis was associated with some measures of attention. Efflux of glutathione into CSF maintains oxidant defense by scavenging free radicals and other reactive oxygen species and is an early event in apoptosis. These mechanisms may be involved in neurologic injury associated with CNS-directed treatment and subsequent cognitive problems. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS)-directed treatment for acute lymphoblastic leukemia, used to prevent disease recurrence in the brain, is essential for survival. Systemic and intrathecal methotrexate, commonly used for CNS-directed treatment, have been associated with cognitive problems during and after treatment. The cortex, hippocampus, and caudate putamen, important brain regions for learning and memory, may be involved in methotrexate-induced brain injury. Objectives of this study were to (1) quantify neuronal degeneration in selected regions of the cortex, hippocampus, and caudate putamen and (2) measure changes in the expression of genes with known roles in oxidant defense, apoptosis/inflammation, and protection from injury. Male Sprague Dawley rats were administered 2 or 4 mg/kg of methotrexate diluted in artificial cerebrospinal fluid (aCSF) or aCSF only into the left cerebral lateral ventricle. Gene expression changes were measured using customized reverse transcription (RT)2 polymerase chain reaction arrays. The greatest percentage of degenerating neurons in methotrexate-treated animals was in the medial region of the cortex; percentage of degenerating neurons in the dentate gyrus and cornu ammonis 3 regions of the hippocampus was also greater in rats treated with methotrexate compared to perfusion and vehicle controls. There was a greater percentage of degenerating neurons in the inferior cortex of control versus methotrexate-treated animals. Eight genes involved in protection from injury, oxidant defense, and apoptosis/inflammation were significantly downregulated in different brain regions of methotrexate-treated rats. To our knowledge, this is the first study to investigate methotrexate-induced injury in selected brain regions and gene expression changes using a rat model of intraventricular drug administration. [ABSTRACT FROM AUTHOR]

Fatigue is a frequent and distressing symptom in children undergoing leukemia treatment; however, little is known about factors influencing this symptom. Antioxidants such as glutathione can decrease symptom severity in adult oncology patients, but no study has evaluated antioxidants’ effects on symptoms in pediatric oncology patients. This study describes fatigue patterns and associations of fatigue with antioxidants represented by reduced glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio among children receiving leukemia treatment. A repeated measures design assessed fatigue and antioxidants among 38 children from two large U.S. cancer centers. Fatigue was assessed among school-age children and by parent proxy among young children. Antioxidants (GSH and GSH/GSSG ratio) were assessed from cerebrospinal fluid at four phases during leukemia treatment. Young children had a steady decline of fatigue from the end of induction treatment through the continuation phase of treatment, but no significant changes were noted among the school-age children. Mean antioxidant scores varied slightly over time; however, the GSH/GSSG ratios in these children were significantly lower than the normal ratio. Mean GSH/GSSG ratios significantly correlated to fatigue scores of the school-age children during early phases of treatment. Children with low mean GSH/GSSG ratios demonstrated oxidative stress. The low ratios noted early in therapy were significantly correlated with higher fatigue scores during induction and postinduction treatment phases. This finding suggests that increased oxidative stress during the more intensive phases of therapy may explain the experience of fatigue children report. [ABSTRACT FROM AUTHOR]

Long-term survivors of childhood leukemia are at risk for neurocognitive impairment, although the neurophysiological basis is not well understood. The purpose of this study was to explore associations between changes in cerebrospinal fluid (CSF) phospholipids and neurocognitive function in children undergoing chemotherapy for acute lymphoblastic leukemia. Seventy-six children were followed prospectively from diagnosis. CSF samples were collected during scheduled lumbar punctures and phospholipids were extracted. Neurocognitive evaluations were conducted annually beginning shortly after diagnosis. Concentrations of sphingomyelin (SM) increased following induction ( p = 0.03) and consolidation ( p = 0.04), while lysophosphatidylcholine (LPC) increased following induction ( p = 0.003). Multivariable analyses demonstrated associations between post-induction SM and motor speed at 1 year ( p < 0.001), 2 years ( p = 0.001) and 3 years ( p = 0.02) following diagnosis. Post-induction LPC was associated with verbal working memory ( p = 0.007). Results indicate that early changes in phospholipids are related to neurocognitive decline and suggest a chemotherapy impact on white matter integrity. [ABSTRACT FROM AUTHOR]

Treatment advances, including central nervous system (CNS) treatment with methotrexate, have led to significant gains in disease-free survival from childhood acute lymphoblastic leukemia (ALL). However, methotrexate has been associated with neurological problems such as declines in cognitive and academic abilities. The purpose of this study was to investigate methotrexate-induced changes in beta-oxidation in children with ALL receiving methotrexate for CNS treatment. Specific aims were to investigate effects of methotrexate on beta-oxidation of the two most prevalent fatty acids (palmitic acid and stearic acid) in cerebrospinal fluid (CSF) samples and correlate the ratio of monounsaturation to saturation of these fatty acids with cognitive and academic abilities. The sample included 12 females and 14 males with low-risk (n = 7), standard-risk (n = 13), or high-risk (n = 6) ALL. Mean age at diagnosis was 94.1 months (SD = 34.4). CSF samples were obtained in conjunction with diagnostic lumbar punctures; subsequent samples were obtained prior to intrathecal methotrexate administration during the induction, consolidation, and continuation phases of treatment. Fatty acids were analyzed by gas chromatography. Results showed a significant increase in the ratio of monounsaturation to saturation of both fatty acids, which was greatest during the most intensive phase of treatment. Ratios of monounsaturated to saturated fatty acids were negatively correlated with full-scale IQ, verbal IQ, and math calculations. Findings suggest that methotrexate alters beta-oxidation and that the resulting increase in fatty acid monounsaturation is related to declines in some domains of cognitive ability. [ABSTRACT FROM AUTHOR]

Difficulties in math are the most frequently reported area of academic deficit in survivors of acute lymphoblastic leukemia (ALL) and the most frequent academic complaint among parents of ALL survivors. However, previous studies that Indies that included measures of math skills have been limited by the use of only a single measure of math skills, most often a measure of written calculations, without any assessment of math reasoning or math application skills. Further, the nature of these math difficulties has not been adequately investigated. The purpose of this study was to examine the performance of ALL survivors using multiple measures of math skills. Performance was compared to a group of healthy controls matched for age and sex as well as to normative levels oilier measures of neuropsychological function were also administered, and the relationships between these measures and the math measures were explored. Converging evidence for math difficulties in ALL survivors compared to healthy controls and normative levels was found. White ALL survivors generally performed within the average range on measures of math skills, math performance was mostly related to memory function and dominant-hand psychomotor speed. By contrast, math performance of healthy children was mostly related to basic reading skills and visual-motor integration. These findings shed light on the nature of math difficulties in ALL survivors and have implications for intervention. [ABSTRACT FROM AUTHOR]

Parents are actively involved in the direct care of their ill child receiving cancer treatment by providing and monitoring therapy and by managing symptoms related to the therapy or to the disease itself. Little is known about parents' perception of what helps or hinders them with their caregiving responsibilities or what effect the caregiving role has on the parent. In this descriptive, exploratory study, 151 parents responded to one or more of six open-ended questions that were part of the newly developed instrument, Care of My Child with Cancer. The 1,280 responses were analyzed using a semantic content analysis technique. The most frequently reported effect on parental caregiving involved negative physical and emotional health. One parent responded, "You feel like you lose all control over your life. It's no longer your own." The most desired forms of assistance with the caregiving role were periodic relief from direct caregiving, ongoing assistance with household responsibilities, and different forms of conveniences that could save time and energy. Two types of actual assistance found to be most helpful by parental caregivers included timely education about their child's health status from health care providers and emotional support from family members, friends, and others. These study findings provide the basis for future interventions that may diminish the effect that caregiving demands place on parents of children with cancer. [ABSTRACT FROM PUBLISHER]

Cancer treatment of the central nervous system has contributed positively to long-term disease-free survival from childhood cancers such as acute leukemia and medulloblastoma. However, intrathecal chemotherapy and whole brain radiation are associated with acute, subacute, and delayed toxicities. The purpose of this review article is to summarize what is known about critical events in prenatal and postnatal brain development; the pathophysiology of radiation and chemotherapy neurotoxicity and clinical manifestations and risk factors for acute, subacute, and delayed toxicities. The importance of long-term follow-up and for multidisciplinary interventions that focus on prevention as well as management of identified problems are addressed. [ABSTRACT FROM PUBLISHER]

In order to advance nursing practice, it is critical that developing the interventions and symptom self-management strategies are evidence-based. This is the first study to focus on stress, symptoms and symptom distress and symptom self-management among men with localized prostate cancer. Prostate cancer is the most common diagnosis and second leading cause of death in American men. Patients with localized prostate cancer may experience unique and multidimensional distressful symptoms that occur from diagnosis through treatment, and thereafter. The most reported distressful symptoms are sexual dysfunction, urinary problem, and bowel problem. These physical and psychological symptoms may alter self care, physical functioning, symptom management, and treatment tolerance. Many studies have focused on health related quality of care, but no one has investigated stress, symptoms and symptom distress, and symptom self- management in localized prostate cancer. The purpose of the study has twofold: (a) to investigate the relationships among stress, symptoms and symptom distress, and symptom self- management and (b) to define the effectiveness of symptom self-management strategies among patients with localized prostate cancer following radical prostatectomy and/ or radiation therapy. The Theory of Unpleasant Symptoms was chosen to guide this prospective research. Stress, symptoms and symptom distress, and symptom self-management are the main concepts of the study. A prospective, descriptive, and cross-sectional research design will be used in this study. Main variables include physiological and psychological stress responses measured by salivary cortisol and Perceived Stress Scale respectively, symptoms and symptom distress measured by The Symptom Index, and symptom self-management measured by The Strategies and Effectiveness Symptom Self-Management Questionnaire. Descriptive statistics, Pearson Product Moment Correlations, and path analysis with structural equation modeling will be used to analyze the data. The SPSS 13.0 and the AMOS 5.0 software will be applied to execute data analysis in this study. In this study, a power of 0.80, an alpha of 0.05, and a moderate effect size of 0.13 are selected. The estimated sample size in this study is 80. The findings have the potential to help health care providers enhance the effectiveness of nursing interventions for stress management and symptom self-management among men with localized prostate cancer. Funding Sources: Student Research Grant from Sigma Theta Tau International [ABSTRACT FROM AUTHOR]

OBJECTIVES: To explore the relationship between biomarkers of oxidative stress and inflmmation in cerebrospinal fluid (CSF) and cognitive function in children receiving maintenance therapy for acute lymphocytic leukemia (ALL). SAMPLE & SETTING: 30 participants aged 4–17 years receiving ALL maintenance therapy at two pediatric cancer centers in the United States. METHODS & VARIABLES: F2-isoprostane (F2-ISoP) and interleukin-8 (IL-8) were evaluated in CSF samples, and cognitive function measures were completed during the first and last cycles of ALL maintenance. The Flanker Inhibitory Control and Attention Test (Flanker) and Dimensional Change Card Sort were completed during the last cycle. RESULTS: During maintenance therapy, IL-8 decreased, and parent reports of children’s cognitive function improved. Higher IL-8 was associated with better parent reports of children’s cognitive function at each timepoint. Higher F2-ISoP levels were associated with lower Flanker scores. IMPLICATIONS FOR NURSING: F2-ISoP may be a useful biomarker in evaluating cognitive dysfunction in children with ALL and merits further investigation. [ABSTRACT FROM AUTHOR]

objectives: The purpose of this study was to investigate parents' knowledge and perceptions about randomization in clinical trials for children with cancer, and to determine whether parents' decisions were influenced by demographic factors, randomization circumstances, the clinical characteristics of the child with cancer, or a combination. materials and methods: This study collected information from 192 parents of patients with various forms of childhood cancer who either accepted or refused randomization. A comparative case-control design was used. The Clinical Investigation Randomization Scale was administered to all participants. This scale included 32 questionnaire items (QIs) pertaining to randomization as well as a mixture of open-ended questions to obtain information about demographic and other factors. results: A predictor model was developed that accurately predicted acceptance or refusal of randomization 87% of the time. Demographic information was found to have less influence than expected on parents' decisions regarding randomization. Knowledge deficits were found among both groups of parents, those who accepted and those who refused randomization. conclusions: What most distinguished parents who refused from those who accepted randomization was not their knowledge and information about randomized clinical trials. By far, the majority of QIs that accurately predicted acceptors and refusers involved parents' beliefs, values, and perceptions. Further research is needed to determine interventions that may enable the healthcare team to provide information and decisional support most effectively to improve the informed consent process. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To describe the impact of central nervous system-directed treatment on attention and its relation to academic outcomes in childhood acute lymphoblastic leukemia (ALL) survivors. SAMPLE & SETTING: 51 children diagnosed with ALL at two pediatric oncology treatment centers in the southwestern United States. METHODS & VARIABLES: A prospective, longitudinal design measured attention after a child was in remission, two years after the start of treatment, and at the end of treatment. Attention measures from the Conners' Continuous Performance Test were grouped into composite subdomains based on a factor structure describing focused attention, hyperactivity/ impulsivity, sustained attention, and vigilance. RESULTS: Children treated for ALL exhibited decreased focused attention, sustained attention, and vigilance during and at the end of treatment when compared to age- and gender-normed references. IMPLICATIONS FOR NURSING: Pediatric oncology nurses are in a position to ask patients and parents about neuropsychological difficulties during ALL treatment. Patients who experience these effects are at risk for decreased academic abilities after treatment. [ABSTRACT FROM AUTHOR]