Cell Context Is the Third Axis of Synergy for the Combination of ATR Inhibition and Cisplatin in Ewing Sarcoma.

Purpose: The importance of cellular context to the synergy of DNA damage response (DDR)-targeted agents is important for tumors with mutations in DDR pathways, but less well-established for tumors driven by oncogenic transcription factors. In this study, we exploit the widespread transcriptional dysregulation of the EWS-FLI1 transcription factor to identify an effective DDR-targeted combination therapy for Ewing sarcoma.

Experimental Design: We used matrix drug screening to evaluate synergy between a DNA-PK inhibitor (M9831) or an ATR inhibitor (berzosertib) and chemotherapy.

CD22 CAR T-cell associated hematologic toxicities, endothelial activation and relationship to neurotoxicity.

Background: Hematologic toxicities, including coagulopathy, endothelial activation, and cytopenias, with CD19-targeted chimeric antigen receptor (CAR) T-cell therapies correlate with cytokine release syndrome (CRS) and neurotoxicity severity, but little is known about the extended toxicity profiles of CAR T-cells targeting alternative antigens. This report characterizes hematologic toxicities seen following CD22 CAR T-cells and their relationship to CRS and neurotoxicity.

Methods: We retrospectively characterized hematologic toxicities associated with CRS seen on a phase 1 study of anti-CD22 CAR T-cells for children and young adults with relapsed/refractory CD22+ hematologic malignancies.

Clinical trials for chimeric antigen receptor T-cell therapy: lessons learned and future directions.

Purpose Of Review: The purpose of this review is to summarize the status and utilization of chimeric antigen receptor T-cell (CAR-T) therapy based on the most recent clinical trials in patients with leukemia and lymphoma. Additionally, this review will highlight limitations in current strategies, discuss efforts in toxicity mitigation, and outline future directions for investigation.

Recent Findings: CD19 targeted CAR-T-cell therapy (CD19-CAR) is highly effective in patients with relapsed/refractory (r/r) B-cell hematologic malignancies.

Neurotoxicity following CD19/CD28ζ CAR T-cells in children and young adults with B-cell malignancies.

Background: Neurotoxicity is an established toxicity of CD19 CAR T-cell therapy; however, there is little information on neurotoxicity in children, adolescents, and young adults (CAYA) receiving CD19/CD28ζ CAR T-cells for B-cell malignancies.

Methods: We analyzed neurotoxicity of CD19/CD28ζ CAR T-cells in CAYA treated on a phase I study (NCT01593696). Assessments included daily inpatient monitoring, caregiver-based neuro-symptom checklist (NSC), exploratory neurocognitive assessments, clinically-indicated imaging, CSF analysis, and systematic cytokine profiling, outcomes of which were associated with cytokine release syndrome (CRS) and treatment response postinfusion.

Influence of a Pediatric Fruit and Vegetable Prescription Program on Child Dietary Patterns and Food Security.

Limited access to fresh foods is a barrier to adequate consumption of fruits and vegetables among youth, particularly in low-income communities. The current study sought to examine preliminary effectiveness of a fruit and vegetable prescription program (FVPP), which provided one USD 15 prescription to pediatric patients during office visits. The central hypothesis was that exposure to this FVPP is associated with improvements in dietary patterns and food security.

Preadmission Diet and Zip Code Influences the Pediatric Critical Care Clinical Course for Infants with Severe Respiratory Illness ( = 187).

We examined preadmission diet and zip code in infants with severe respiratory illness in the pediatric critical care unit. Patients aged 0 to 5 months admitted to the Helen DeVos Children's Hospital from January 2011 to May 2017 (  = 187), as exclusively formula, exclusively breastfed or mixed diet were included. Formula-fed infants (  = 88; 47%) clustered to zip codes with lower median incomes (<0.

F-FLT Positron Emission Tomography (PET) is a Pharmacodynamic Marker for EWS-FLI1 Activity and Ewing Sarcoma.

Ewing sarcoma is a bone and soft-tissue tumor that depends on the activity of the EWS-FLI1 transcription factor for cell survival. Although a number of compounds have been shown to inhibit EWS-FLI1 in vitro, a clinical EWS-FLI1-directed therapy has not been achieved. One problem plaguing drug development efforts is the lack of a suitable, non-invasive, pharmacodynamic marker of EWS-FLI1 activity.