Calaspargase pegol and pegaspargase cause similar hepatosteatosis in mice.

Not available.

Budget impact analysis of TPMT and NUDT15 pharmacogenomic testing for 6-mercaptopurine in pediatric acute lymphoblastic leukemia patients.

Background: Pharmacogenomic testing identifies gene polymorphisms impacting drug metabolism, aiding in optimizing treatment efficacy and minimizing toxicity, thus potentially reducing healthcare utilization. 6-Mercaptopurine metabolism is affected by thiopurine methyltransferase ( TPMT ) and nudix hydrolase 15 ( NUDT15 ) polymorphisms. We sought to estimate the budget impact of preemptive pharmacogenomic testing for these genes in pediatric acute lymphoblastic leukemia (ALL) patients from an institutional perspective.

Optimizing early phase clinical trial washout periods: a report from the Therapeutic Advances in Childhood Leukemia and Lymphoma consortium.

Background: The National Cancer Institute (NCI) issued a 2021 memorandum adopting the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) task force recommendations to broaden clinical study eligibility criteria. They recommended that washout periods be eliminated for most prior cancer therapy and when required to utilize evidence- and/or rationale-based criteria. The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) consortium responded to this guidance.

Ultrasound-Assisted Catheter-Directed Thrombolysis for the Management of Pulmonary Embolism: .

Current guidelines recommend anticoagulation alone for low-risk pulmonary embolism (PE) with the addition of systemic thrombolysis for high-risk PE. However, treatment recommendations for intermediate-risk PE are not well-defined. Due to bleeding risks associated with systemic thrombolysis, ultrasound-assisted catheter-directed thrombolysis (USAT) has evolved as a promising treatment modality.

Lack of benefit from premedication for pegylated asparaginase during pediatric acute lymphoblastic leukemia/lymphoma therapy: A side-by-side comparison.

Background: Pegylated l-asparaginase (PEG) is integral to treatment regimens for acute lymphoblastic leukemia (ALL) and lymphoma. Hypersensitivity reactions (HSRs) to PEG are common and can preclude continued administration. Data supporting recommendations for universal premedication (UPM) prior to PEG infusion to reduce incidence of HSRs are limited; UPM has become common practice.

Intravenous N-Acetylcysteine to Prevent Cisplatin-Induced Hearing Loss in Children: A Nonrandomized Controlled Phase I Trial.

Purpose: Cisplatin-induced hearing loss (CIHL) is common and permanent. As compared with earlier otoprotectants, we hypothesized N-acetylcysteine (NAC) offers potential for stronger otoprotection through stimulation of glutathione (GSH) production. This study tested the optimal dose, safety, and efficacy of NAC to prevent CIHL.

COVID-19 outcomes in children, adolescents and young adults with cancer.

Pediatric oncology patients are at risk for poor outcomes with respiratory viral infections. Outcome data for COVID-19 in children and young adults with cancer are needed; data are sparse for obese/overweight and adolescent and young adult subgroups. We conducted a single center cohort study of COVID-19 outcomes in patients younger than 25 years with cancer.

Development of Thermoplastic Composite Reinforced Ultra-High-Performance Concrete Panels for Impact Resistance.

In order to improve flexural and impact performance, thin panels of steel fiber-reinforced ultra-high performance concrete (UHPC) were further reinforced with external layers of continuous fiber-reinforced thermoplastic (CFRTP) composites. CFRTP sheets were bonded to 305 × 305 × 12 mm UHPC panels using two different techniques. First, unidirectional E-glass fiber-reinforced tapes of polyethylene terephthalate glycol-modified (PETG) were arranged in layers and fused to the UHPC panels through thermoforming.

Association of body mass index with toxicity and survival in pediatric patients treated with cisplatin-containing regimens.

Malnutrition is associated with treatment-related toxicities (TRT) in adults with solid tumors and in children with leukemia. Few studies have assessed whether malnutrition in pediatric patients treated for solid tumors impacts risk for TRT, relapse, and/or survival. To address this knowledge gap, this retrospective study evaluated the association between body mass index (BMI) at diagnosis, and imputed BMI during therapy, on the prevalence of TRT, specific toxicities, relapse, and survival in pediatric patients with solid tumors treated with cisplatin-containing regimens.

Intra-individual Pharmacokinetic Variability of Intravenous Busulfan in Hematopoietic Stem Cell-Transplanted Children.

Background: Busulfan therapeutic drug monitoring (TDM) is necessary to better achieve the target exposure in children before hematopoietic stem cell transplantation (HSCT). However, TDM-based dosing may be challenging if intra-individual pharmacokinetic variability (also denoted inter-occasion variability [IOV]) occurs during therapy.

Objectives: The objectives of this study were to describe and quantify busulfan IOV in children, and to investigate its potential determinants.

Improving the Timeliness of Chemotherapy Administration in the Bone Marrow Transplant Unit.

Patients undergoing hematopoietic stem cell transplantation (HSCT) are often admitted to the hospital the day they are due to begin their conditioning regimen. Timely initiation of chemotherapy during regular work hours is important for patient safety, because during the night shift fewer physicians and pharmacists are available for urgent or unexpected matters. A review of the data at our institution from October 2017 to August 2018 showed that approximately one-third of our chemotherapy was started during the night shift (after 19:00), and the average time from admission to start of chemotherapy was over 8 hours.

Electrospinning of Cellulose Nanocrystal-Filled Poly (Vinyl Alcohol) Solutions: Material Property Assessment.

Poly (vinyl alcohol) (PVA) and cellulose nanocrystals (CNC) random composite mats were prepared using the electrospinning method. PVA/CNC mats were reinforced with weight concentrations of 0, 20 and 50% CNC (/) relative to PVA. Scanning electron microscopy was used to measure the fiber diameter, which ranged from 377 to 416 nm.

Maximal concentration of intravenous busulfan as a determinant of veno-occlusive disease: a pharmacokinetic-pharmacodynamic analysis in 293 hematopoietic stem cell transplanted children.

Veno-occlusive disease (VOD) is a severe adverse reaction to busulfan-containing regimens used in the preparation of children for hematopoietic stem cell transplantation (HSCT). We conducted a retrospective analysis of data to examine determinants of VOD in children who received IV busulfan for HSCT conditioning. Busulfan PK parameters as well as various indices (maximal concentration-Cmax, area under the concentration-time curve-AUC) were estimated using a validated Bayesian approach.

Repurposing Cytarabine for Treating Primary Effusion Lymphoma by Targeting Kaposi's Sarcoma-Associated Herpesvirus Latent and Lytic Replications.

Oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically linked to primary effusion lymphoma (PEL), an aggressive and nontreatable malignancy commonly found in AIDS patients. In this study, we performed a high-throughput screening of 3,731 characterized compounds and identified cytarabine, approved by the FDA for treating numerous types of cancer, as a potent inhibitor of KSHV-induced PEL. We showed the high efficacy of cytarabine in the growth inhibition of various PEL cells by inducing cell cycle arrest and apoptosis.

Phase I trial of dasatinib, lenalidomide, and temozolomide in children with relapsed or refractory central nervous system tumors.

Single agent studies targeting the tumor microenvironment in central nervous system (CNS) tumors have largely been disappointing. Combination therapies targeting various pathways and cell types may be a more effective strategy. In this phase I study, we evaluated the combination of dasatinib, lenalidomide, and temozolomide in children with relapsed or refractory primary CNS tumors.

Method to reinforce polylactic acid with cellulose nanofibers via a polyhydroxybutyrate carrier system.

The elastic moduli of PLA reinforced with 5 and 10wt.% CNF with the carrier, at a frequency (ω) of 0.07, were 67% and 415% higher, respectively, than that of neat PLA.

Accurately Achieving Target Busulfan Exposure in Children and Adolescents With Very Limited Sampling and the BestDose Software.

Background: Busulfan dose adjustment is routinely guided by plasma concentration monitoring using 4-9 blood samples per dose adjustment, but a pharmacometric Bayesian approach could reduce this sample burden.

Methods: The authors developed a nonparametric population model with Pmetrics. They used it to simulate optimal initial busulfan dosages, and in a blinded manner, they compared dosage adjustments using the model in the BestDose software to dosage adjustments calculated by noncompartmental estimation of area under the time-concentration curve at a national reference laboratory in a cohort of patients not included in model building.

Clinical and microbiologic outcomes of quinolone prophylaxis in children with acute myeloid leukemia.

Background: Intensifying treatment for pediatric acute myeloid leukemia (AML) has improved survival, with infections now being a leading cause of morbidity. Because quinolone prophylaxis is effective in adults with AML and in transplant populations, ciprofloxacin prophylaxis (CPx) was introduced as the standard for pediatric AML. We report here the impact of CPx in this population.

Testing of various membranes for use in a novel sediment porewater isolation chamber for infaunal invertebrate exposure to PCBs.

In benthic sediment bioassays, determining the relative contribution to exposure by contaminants in overlying water, porewater, and sediment particles is technically challenging. The purpose of the present study was to assess the potential for membranes to be utilized as a mechanism to allow freely dissolved hydrophobic organic contaminants into a pathway isolation exposure chamber (PIC) while excluding all sediment particles and dissolved organic carbon (DOC). This investigation was conducted in support of a larger effort to assess contaminant exposure pathways to benthos.

Efficacy and tolerability of intravenous pentamidine isethionate for Pneumocystis jiroveci prophylaxis in a pediatric oncology population.

Cancer therapy routinely requires Pneumocystis jiroveci prophylaxis. In those intolerant of trimethoprim/sulfamethoxazole, aerosolized pentamidine is convenient and effective. Intravenous pentamidine is often substituted in young children but its efficacy remains controversial.

Pediatric patients with intravascular devices: polymicrobial bloodstream infections and risk factors.

A retrospective study was conducted, including 61 patients with long-term intravascular devices (IVDs) admitted to the Childrens Hospital Los Angeles with diverse underlying diseases, different types of catheters, and culture-proven catheter-related bloodstream infections (BSIs). Within these patients, 125 catheter-related BSIs occurred, and the incidence of monomicrobial and polymicrobial BSIs was evaluated. Risk factors for polymicrobial BSIs were determined.

Voriconazole pharmacokinetics and pharmacodynamics in children.

Background: Voriconazole pharmacokinetic and pharmacodynamic data are lacking in children.

Methods: Records at the Childrens Hospital Los Angeles were reviewed for children with > or =1 serum voriconazole concentration measured from 1 May 2006 through 1 June 2007. Information on demographic characteristics, dosing histories, serum concentrations, toxicity and survival, and outcomes was obtained.

The effects of Campath 1H upon graft-versus-host disease, infection, relapse, and immune reconstitution in recipients of pediatric unrelated transplants.

Graft-versus-host disease (GVHD) is a cause of serious morbidity and mortality in >50% of recipients of unrelated hematopoietic stem cell transplantation (HSCT). We performed a trial using Campath 1 H pre- and post-HSCT in an attempt to decrease the incidence of GVHD without increasing the risk of infection or relapse. Patients were retrospectively compared to a population of patients who received antithymocyte globulin (ATG) pre- and post-HSCT.