Patient-reported outcomes and neurotoxicity markers in patients treated with bispecific LV20.19 CAR T cell therapy.

Background: With the rising number of chimeric antigen receptor (CAR) T cell treated patients, it is increasingly important to understand the treatment's impact on patient-reported outcomes (PROs) and, ideally, identify biomarkers of central nervous system (CNS) adverse effects. Methods: The purpose of this exploratory study was to assess short-term PROs and serum kynurenine metabolites for associated neurotoxicity among patients treated in an anti-CD20, anti-CD19 (LV20.19) CAR T cell phase I clinical trial (NCT03019055). Fifteen CAR T treated patients from the parent trial provided serum samples and self-report surveys 15 days before and 14, 28, and 90 days after treatment. Results: Blood kynurenine concentrations increased over time in patients with evidence of neurotoxicity (p = 0.004) and were increased in self-reported depression (r = 0.52, p = 0.002). Depression improved after CAR T infusion (p = 0.035). Elevated 3-hydroxyanthranilic acid (3HAA) concentrations prior to cell infusion were also predictive of neurotoxicity onset (p = 0.031), suggesting it is a biomarker of neurotoxicity following CAR T cell therapy. Conclusions: Elevated levels of kynurenine pathway metabolites among CAR T cell recipients are associated with depressed mood and neurotoxicity. Findings from this exploratory study are preliminary and warrant validation in a larger cohort.

This study examined the impact of chimeric antigen receptor (CAR) T cell therapy­a therapy that gets immune cells to fight cancer by changing them in the lab to find and destroy cancer cells­on blood markers associated with depression, anxiety, pain, fatigue, and poor sleep. Fifteen CAR T cell patients provided blood samples and completed surveys before and three timepoints after treatment. We found that the amount of kynurenine, a normal blood constituent, and related molecules was higher in patients who experienced significant CAR T cell side effects on the brain and in patients reporting more depression. These results identify the excessive elevation of blood constituents related to the mood that may also be associated with depression and brain dysfunction following CAR T. These blood constituents could potentially be used as markers and targeted with interventions to prevent brain dysfunction.

Multicenter Analysis of Transport Destinations for Pediatric Prehospital Patients.

BACKGROUND: Although all emergency departments (EDs) should be ready to treat children, some may have illnesses or injuries that require higher-level pediatric resources that are not available at all hospitals. There are no national guidelines for emergency medical services (EMS) providers about when to directly transport children to hospitals with higher-level pediatric resources, with the exception of severe trauma. Variability exists in EMS protocols about when children warrant transport to hospitals with higher-level pediatric care. OBJECTIVE: The objective was to determine how frequently pediatric patients are transported by EMS to hospitals with higher-level pediatric resources and to evaluate distribution patterns based on illness and injury severity. METHODS: We conducted a retrospective analysis of all pediatric (age 0-18 years) transports in three large EMS systems between November 2014 and November 2016. Each community had a hospital with higher-level pediatric resources that was within a 30-minute transport time from any location. Patients were included if they were transported by ground ambulance and the request originated in the 9-1-1 system. We assessed the frequency of transports to a hospital with higher-level pediatric resources. Data were stratified by chief complaint of illness or injury and severity. Potential risk for severe injury was defined as meeting the physiologic step of the field triage guidelines and potential risk for severe illness was defined as having an abnormal vital sign after adjusting for patient age. RESULTS: A total of 41,345 pediatric patients were transported by a participating EMS agency to an ED and had complete destination data. A total of 55% of all EMS-transported pediatric patients were transported to a hospital with higher-level pediatric resources. There was variation by site (range = 45%-71%) in the percentage of children who went to a hospital with higher-level pediatric resources. Patients over 15 years of age went to general EDs (57%) more often than younger patients. When stratified by severity, 60% of those with potentially severe illness and 74% of those with potentially severe trauma were transported to a hospital with higher-level pediatric resources. CONCLUSIONS: EMS providers commonly transport children to hospitals with higher-level pediatric resources. However, more than one-quarter of children with potentially severe injuries and illnesses are transported to general EDs.