Episodes of acute methotrexate-related neurotoxicity linked to compromised long-term neurocognitive function.

Methotrexate is a critical component of curative chemotherapy for pediatric acute lymphoblastic leukemia (ALL), but is associated with neurotoxicity. Information on long-term outcomes following an acute neurotoxic event is limited. Therefore, this report compares neurocognitive performance more than 12 months post diagnosis (mean = 4 years) between ALL patients with (n = 25) and without (n = 146) a history of acute neurotoxicity.

Preferences for survivorship education and delivery among Latino and non-Latino childhood cancer survivors and caregivers.

Purpose: To assess survivor and parent perceptions of the long-term survivor visit and preferences regarding accessing health information, survivorship education, and support networks in rural and metropolitan regions of Texas.

Methods: Leveraging the multi-institutional Survivorship and Access to Care for Latinos to Understand Disparities (SALUD) cohort, we administered a 26-item bilingual survey to adult survivors of childhood cancer and parents of younger survivors. Characteristics and responses were compared between survivors vs.

Identification of USP9X as a leukemia susceptibility gene.

We recently reported that children with multiple birth defects have a significantly higher risk of childhood cancer. We performed whole-genome sequencing on a cohort of probands from this study with birth defects and cancer and their parents. Structural variant analysis identified a novel 5 kb de novo heterozygous inframe deletion overlapping the catalytic domain of USP9X in a female proband with multiple birth defects, developmental delay, and B-cell acute lymphoblastic leukemia (B-ALL).

Symptoms, Physical Activity, and Biomarkers in Children at the End of Leukemia Maintenance Therapy.

Symptoms in children with acute lymphocytic leukemia (ALL) change over the trajectory of treatment but little is known about their symptoms as treatment ends. Physical activity may help decrease symptom distress and is vital for ongoing development. The role of biomarkers in symptom science is emerging.

Ethnic-specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high-dose methotrexate.

Background: High-dose methotrexate (HD-MTX; 5000 mg/m ) is an important component of curative therapy in many treatment regimens for high-risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose-limiting neurotoxicity, which may disproportionately affect Latino children. This study evaluated risk factors for neurotoxicity after HD-MTX in an ethnically diverse population of patients with ALL.

A Prospective Evaluation of Fatigue in Pediatric Brain Tumor Patients Treated With Radiation Therapy.

Fatigue is a well-established consequence of cranial radiotherapy in survivors of pediatric brain tumor, but less is known about acute fatigue during radiotherapy treatment. This study aimed to longitudinally evaluate fatigue in newly diagnosed pediatric patients with brain tumors during treatment. Primary caregivers of pediatric patients with brain tumors completed the proxy-reported Parent Fatigue Scale assessments prior to radiotherapy and weekly during radiotherapy treatment.

Reducing external ventricular drain associated ventriculitis: An improvement project in a level 1 trauma center.

Background: External ventricular drain (EVD)-associated infections have a negative impact on healthcare cost and patient outcomes. Practice variation in EVD management may place patients at increased risk for EVD-associated infection. This project aimed to evaluate the impact of implementing an interprofessional evidence-based EVD bundle of care on reduction of EVD-related ventriculitis rates.

Association between fatigue and sleep disturbances during treatment for pediatric acute lymphoblastic leukemia and posttreatment neurocognitive performance.

Background: Survivors of pediatric acute lymphoblastic leukemia (ALL) are at increased risk of neurocognitive weakness in the areas of attention, executive function, and processing speed. Although fatigue and sleep disturbances are frequent complications of ALL therapy and associated with cognitive functions, the impact of fatigue and sleep profiles during active ALL treatment on posttreatment neurocognitive performance has received limited attention.

Methods: Pediatric patients (n = 120) with ALL (diagnosed 2011-2016) who completed fatigue and sleep questionnaires at four time points during active treatment were enrolled in a study of neurocognitive performance.

Biomarkers and Cognitive Function in Children and Adolescents During Maintenance Therapy for Leukemia.

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.

Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.

Metabolomics may shed light on treatment response in childhood acute lymphoblastic leukemia (ALL), however, most assessments have analyzed bone marrow or cerebrospinal fluid (CSF), which are not collected during all phases of therapy. Blood is collected frequently and with fewer risks, but it is unclear whether findings from marrow or CSF biomarker studies may translate. We profiled end-induction plasma, marrow, and CSF from N = 10 children with B-ALL using liquid chromatography-mass spectrometry.

Symptom Clusters, Physical Activity, and Quality of Life: A Latent Class Analysis of Children During Maintenance Therapy for Leukemia.

Background: Children undergoing treatment for acute lymphocytic leukemia (ALL) report co-occurring symptoms of fatigue, sleep disturbances, and depression as a symptom cluster. Physical activity (PA) may influence symptom severity and quality of life (QOL).

Objectives: This study examined changes in symptoms and QOL during ALL maintenance in children categorized by symptom cluster and explored the influence of PA and symptoms on QOL.

Prospective patient-reported symptom profiles associated with pediatric acute lymphoblastic leukemia relapse.

Purpose: Despite improvements in frontline pediatric acute lymphoblastic leukemia (ALL) treatment, relapse remains a concern. Research in adult cancer patients suggests that patient-reported symptoms may predict survival, but the relationship between symptoms and relapse for pediatric ALL has received little attention.

Methods: Pediatric patients with ALL (age 2-18 years) and/or their primary caregivers completed symptom surveys at the end of induction, start of delayed intensification (DI), start of maintenance cycle 1 (MC1), and start of maintenance cycle 2 (MC2).

Cerebrospinal Fluid Metabolomic Profiles Associated With Fatigue During Treatment for Pediatric Acute Lymphoblastic Leukemia.

Context: Cancer-related fatigue (CRF) is one of the most distressing and persistent symptoms reported during pediatric acute lymphoblastic leukemia (ALL) therapy; however, information on the pathways underlying CRF severity is limited.

Objectives: We conducted global metabolomics profiling of cerebrospinal fluid (CSF) samples to provide insight into the underlying mechanisms of CRF.

Methods: Fatigue in pediatric ALL patients (2012-2017) was assessed during postinduction therapy approximately six months after diagnosis.

The Longitudinal Parallel Process Analysis of Biomarkers of Oxidative Stress, Symptom Clusters, and Cognitive Function in Children With Leukemia.

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.

Influence of Inflammatory and Oxidative Stress Pathways on Longitudinal Symptom Experiences in Children With Leukemia.

Purpose: The purpose of this study was to explore the influence of oxidative stress (F2-isoprostanes) and inflammatory (interleukin [IL]-8) biomarkers on symptom trajectories during the first 18 months of childhood leukemia treatment.

Method: A repeated-measures design was used to evaluate symptoms experienced by 218 children during treatment. A symptom cluster (fatigue, pain, and nausea) was explored over four time periods: initiation of post-induction therapy, 4 and 8 months into post-induction therapy, and the beginning of maintenance therapy (12 months postinduction).

Impact of Childhood Leukemia Treatment on Attention Measured by the Continuous Performance Test Factor Structure.

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.

Childhood Cancer Symptom Cluster: Leukemia and Health-Related Quality of Life.

Objectives: To examine the relationship of the Childhood Cancer Symptom Cluster-Leukemia (CCSC-L) with health-related quality of life (HRQOL).

Sample & Setting: 327 children receiving treatment for acute lymphoblastic leukemia from four pediatric oncology programs across the United States.

Methods & Variables: Participants completed fatigue, sleep disturbance, pain, nausea, and depression symptom questionnaires at four time points; these symptoms comprised the CCSC-L.

Disparities in Neurotoxicity Risk and Outcomes among Pediatric Acute Lymphoblastic Leukemia Patients.

Methotrexate chemotherapy can be associated with neurologic complications during therapy and long-term neurologic deficits. This study evaluated demographic and clinical factors associated with incidence of methotrexate neurotoxicity and described the impact of neurotoxicity on acute lymphoblastic leukemia (ALL) therapy in pediatric patients. Patients were enrolled between 2012 and 2017 from three pediatric cancer treatment centers in the United States.

Physical Activity, the Childhood Cancer Symptom Cluster-Leukemia, and Cognitive Function: A Longitudinal Mediation Analysis.

Background: Children undergoing leukemia treatment report co-occurring symptoms of fatigue, sleep disturbances, pain, nausea, and depression as a symptom cluster. Physical activity (PA) is essential for development and may influence symptom severity. Children with leukemia are at risk of cognitive impairments from central nervous system therapies.

Influence of Nitrosative Stress on Fatigue During Childhood Leukemia Treatment.

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.

Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia.

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.

Declines Noted in Cognitive Processes and Association With Achievement Among Children With Leukemia.

Purpose/objectives: To assess change in specific cognitive processes during treatment with chemotherapy only among children with acute lymphoblastic leukemia (ALL). 
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Design: A prospective, repeated measures design.

Symptom Trajectories in Children Receiving Treatment for Leukemia: A Latent Class Growth Analysis With Multitrajectory Modeling.

Context: Cancer treatment symptoms play a major role in determining the health of children with cancer. Symptom toxicity often results in complications, treatment delays, and therapy dose reductions that can compromise leukemia therapy and jeopardize chances for long-term survival. Critical to understanding symptom experiences during treatment is the need for exploration of "why" inter-individual symptom differences occur; this will determine who may be most susceptible to treatment toxicities.

Fatigue and Oxidative Stress in Children Undergoing Leukemia Treatment.

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.