Novel thermoplastic microvalves based on an elastomeric cyclic olefin copolymer.

Microfluidic systems combine multiple processing steps and components to perform complex assays in an autonomous fashion. To enable the integration of several bio-analytical processing steps into a single system, valving is used as a component that directs fluids and controls introduction of sample and reagents. While elastomer polydimethylsiloxane has been the material of choice for valving, it does not scale well to accommodate disposable integrated systems where inexpensive and fast production is needed.

Tailored approach to participant recruitment and retention to maximize health equity in pediatric cancer research.

Background: Lack of diversity in participants throughout the research process limits the generalizability of findings and may contribute to health disparities. There are unique challenges to recruitment of families to pediatric cancer research studies, especially for those from disadvantaged backgrounds. Thus, there is a need to evaluate the most effective recruitment and retention strategies to optimize equitable recruitment of diverse participants.

Caregiver perceptions of child heath behaviors and weight during treatment for acute lymphoblastic leukemia.

Background: Changes in health behaviors and weight are common during the early phases of pediatric acute lymphoblastic leukemia treatment, and may negatively impact treatment tolerability. Given that ALL is most prevalent in children, caregivers play an essential role in shaping health behaviors during treatment. This study presents a qualitative analysis of semi-structured interviews with caregivers of youth in the early phases of ALL treatment.

Family Rules and Routines During the Early Phases of Pediatric Cancer Treatment: Associations With Child Emotional and Behavioral Health.

Objective: Consistent family rules and routines promote positive adaptation to stress and may be protective to child emotional and behavioral functioning. Few studies have quantified family engagement in these behaviors during pediatric cancer treatment or examined associations with child emotional and behavioral health.

Methods: In this cross-sectional observational study, 86 primary caregivers of youth ages 2-14 years (M = 7.

Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma.

Tisagenlecleucel is indicated for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; we examined the effects of humoral and cellular immune responses to tisagenlecleucel on clinical outcomes using 2 validated assays. Data were pooled from the ELIANA (registered at www.

Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia.

Background: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse.

Methods: A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel.

Results of a phase 2, multicenter, single-arm, open-label study of lenalidomide in pediatric patients with relapsed or refractory acute myeloid leukemia.

Background: Outcomes after relapse remain poor in pediatric patients with acute myeloid leukemia (AML), and new therapeutic approaches are needed. Lenalidomide has demonstrated activity in adults with lower risk myelodysplastic syndromes and older adults with relapsed or refractory (R/R) AML.

Methods: In this phase 2 study (NCT02538965), pediatric patients with R/R AML who received two or more prior therapies were treated with lenalidomide (starting dose 2 mg/kg/day on days 1-21 of each 28-day cycle) for a maximum of 12 cycles.

Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection.

Background: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in the course during clinical trials due to concern for potential negative effect on efficacy and persistence.

Chlorhexidine gluconate bathing in children with cancer or those undergoing hematopoietic stem cell transplantation: A double-blinded randomized controlled trial from the Children's Oncology Group.

Background: To the authors' knowledge, information regarding whether daily bathing with chlorhexidine gluconate (CHG) reduces central line-associated bloodstream infection (CLABSI) in pediatric oncology patients and those undergoing hematopoietic stem cell transplantation (HCT) is limited.

Methods: In the current multicenter, randomized, double-blind, placebo-controlled trial, patients aged ≥2 months and <22 years with cancer or those undergoing allogeneic HCT were randomized 1:1 to once-daily bathing with 2% CHG-impregnated cloths or control cloths for 90 days. The primary outcome was CLABSI.

Application of 2016 WHO classification in the diagnosis of paediatric high-grade -negative mature B-cell lymphoma with Burkitt-like morphological features.

Aims: Historically, there has been no consensus on the diagnostic classification of high-grade B-cell lymphoma (HGBCL) with morphological features of Burkitt lymphoma (BL) but no gene rearrangement (-negative). The 2016 WHO classification of tumours of haematopoietic and lymphoid tissues has shed some light on this field with the modification of the grey-zone lymphoma with features intermediate between BL and diffuse large B-cell lymphoma, and the creation of several new entities. The aim of this study was to investigate how the revised WHO classification affects our practice in diagnosing these lymphomas in children.

Treatment of children with relapsed and refractory acute lymphoblastic leukemia with mitoxantrone, vincristine, pegaspargase, dexamethasone, and bortezomib.

Background: The treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) in children is challenging and new treatment options are needed. Bortezomib is a proteasome inhibitor with activity in pediatric acute lymphoblastic leukemia. Adding bortezomib to standard reinduction chemotherapy in relapsed and refractory pediatric ALL has produced very good response rates in prior studies.

Desensitization to pegaspargase in children with acute lymphoblastic leukemia and lymphoblastic lymphoma.

Hypersensitivity to pegaspargase is associated with inferior survival in pediatric patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. In the past year, drug-supply shortages have led to the lack of an available alternative to pegaspargase. Rather than omit asparaginase from the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma patients with hypersensitivity to pegaspargase, we continued pegaspargase treatments for nine pediatric patients, utilizing a rapid desensitization protocol.

Tisagenlecleucel Model-Based Cellular Kinetic Analysis of Chimeric Antigen Receptor-T Cells.

Tisagenlecleucel is a chimeric antigen receptor-T cell therapy that facilitates the killing of CD19 B cells. A model was developed for the kinetics of tisagenlecleucel and the impact of therapies for treating cytokine release syndrome (tocilizumab and corticosteroids) on expansion. Data from two phase II studies in pediatric and young adult relapsed/refractory B cell acute lymphoblastic leukemia were pooled to evaluate this model and evaluate extrinsic and intrinsic factors that may impact the extent of tisagenlecleucel expansion.

Feasibility of Outpatient High-Dose Methotrexate Infusions in Pediatric Patients With B-Lineage Acute Lymphoblastic Leukemia.

High-dose methotrexate (MTX) given in four hospitalizations during interim maintenance for high-risk pediatric B-lineage acute lymphocytic leukemia significantly improves survival but increases resource utilization. Children remain hospitalized for intravenous hydration and blood or urine monitoring until MTX clearance parameters are reached. Improved supportive care, extended infusion center hours, and pediatric home health expertise afford alternatives to prolonged hospital admissions, potentially offering quality, cost-effective approaches that positively impact the delivery of care.

Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia.

Purpose: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

Patients And Methods: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

Results: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders ( = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( = 8; 74% and 104% higher geometric mean Cmax and AUC0-28d, respectively) with persistence measurable beyond 2 years in responding patients.

Pharmacokinetics of two 6-mercaptopurine liquid formulations in children with acute lymphoblastic leukemia.

Background: A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation.

Methods: Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts.

Early Discharge of Neutropenic Pediatric Oncology Patients Admitted With Fever.

Background: Fever and neutropenia (FN) is a common complication of pediatric oncology therapy and accounts for a large number of hospital admissions. Standard therapy for FN includes hospital admission and empiric antibiotics. Strict adherence to this practice leads to prolonged hospitalizations that may be unnecessary for patients at low risk of having an underlying significant infection.

Characteristics of Children With Cancer Discharged or Admitted From the Emergency Department.

Background: Emergency department (ED) utilization by children with cancer is poorly understood. Among children with cancer, we explored reasons for ED visits and factors associated with admission within U.S.

Relative defects in mucosal immunity predict acute graft-versus-host disease.

Impairment of gut mucosal immunity by the transplant process could facilitate translocation of commensal bacteria and thereby augment the graft-versus-host response. To begin to assess the influence of gut mucosal immunity on the development of acute graft-versus-host disease (GVHD), we conducted a prospective study in 24 pediatric allogeneic hematopoietic cell transplant recipients, assessing 4 fecal markers of mucosal immunity: calprotectin, soluble CD8 (sCD8), soluble intracellular adhesion molecule 1, and β-defensin-2. Stool samples were collected prospectively on transplant days 0, +5, +10, and +15 and analyzed by ELISA.

Comparison of hypersensitivity reactions to PEG-asparaginase in children after intravenous and intramuscular administration.

Introduction: Polyethylene-glycolated (PEG)-asparaginase (PEG-ASP) is a crucial component of pediatric acute lymphoblastic leukemia therapy. Although hypersensitivity reactions to PEG-ASP occur less frequently than with other formulations, they are not uncommon and have an adverse impact on patient outcomes. Intravenous (IV) administration of PEG-ASP reduces patient pain and anxiety and is being used with increasing frequency in children.

Pediatric relapsed or refractory leukemia: new pharmacotherapeutic developments and future directions.

Over the past 50 years, numerous advances in treatment have produced dramatic increases in the cure rates of pediatric leukemias. Despite this progress, the majority of children with relapsed leukemia are not expected to survive. With current chemotherapy regimens, approximately 15 % of children with acute lymphoblastic leukemia and 45 % of children with acute myeloid leukemia will have refractory disease or experience a relapse.

Late effects of childhood leukemia therapy.

As survival rates for children treated for childhood cancers become significantly better, the focus is increasingly on determining the late effects of treatments and the best ways to monitor for them and prevent their occurrence. This review focuses on recent literature discussing the late effects of treatment in patients treated for acute myeloid leukemia and acute lymphoblastic leukemia during childhood. The late effects of therapy for childhood leukemia include secondary malignancy, cardiotoxicity, obesity, endocrine abnormalities, reproductive changes, neurocognitive deficits, and psychosocial effects.