Dataset Information

EEG Correlates of Delirium in Children and Young Adults With CD19-Directed CAR T Cell Treatment-Related Neurotoxicity.

ABSTRACT:

Introduction

EEG patterns in chimeric antigen receptor T cell treatment-associated neurotoxicity (immune effector cell-associated neurotoxicity syndrome) have not yet been systematically studied. We tested the hypothesis that EEG background abnormalities in immune effector cell-associated neurotoxicity syndrome correlate with clinical signs of neurotoxicity. In addition, we describe ictal and interictal EEG patterns to better understand the natural history of immune effector cell-associated neurotoxicity syndrome-associated seizures.

Methods

EEGs were obtained in 19 of 100 subjects in a prospective cohort study of children and young adults undergoing CD19-directed chimeric antigen receptor T cell therapy. We classified the EEG background on a severity scale of 0 to 5 during 30-minute epochs. EEG grades were compared with neurotoxicity scored by Common Terminology Criteria for Adverse Events and Cornell Assessment of Pediatric Delirium scores. Descriptive analysis was conducted for ictal and interictal EEG abnormalities.

Results

EEG background abnormality scores correlated well with Common Terminology Criteria for Adverse Events neurotoxicity scores (P = 0.0022) and Cornell Assessment of Pediatric Delirium scores (P = 0.0085). EEG was better able to differentiate the severity of coma patterns compared with the clinical scores. The EEG captured electroclinical seizures in 4 of 19 subjects, 3 of whom had additional electrographic-only seizures. Seizures most often arose from posterior head regions. Interictal epileptiform discharges were focal, multifocal, or lateralized periodic discharges. No seizures or interictal epileptiform abnormalities were seen in subjects without previous clinical seizures.

Conclusions

Continuous EEG monitoring is high yield for seizure detection in high-risk chimeric antigen receptor T cell patients, and electrographic-only seizures are common. Increasing severity of EEG background abnormalities correlates with increasing neurotoxicity grade.

SUBMITTER: Gust J

PROVIDER: S-EPMC7292745 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

EEG Correlates of Delirium in Children and Young Adults With CD19-Directed CAR T Cell Treatment-Related Neurotoxicity.

Gust Juliane J Annesley Colleen E CE Gardner Rebecca A RA Bozarth Xiuhua X

Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society 20210301 2

<h4>Introduction</h4>EEG patterns in chimeric antigen receptor T cell treatment-associated neurotoxicity (immune effector cell-associated neurotoxicity syndrome) have not yet been systematically studied. We tested the hypothesis that EEG background abnormalities in immune effector cell-associated neurotoxicity syndrome correlate with clinical signs of neurotoxicity. In addition, we describe ictal and interictal EEG patterns to better understand the natural history of immune effector cell-associa ...[more]

PMID: 31851018

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Project description:Chimeric antigen receptor (CAR) T-cell-associated cytokine release syndrome (CRS) may present with tachycardia, hemodynamic instability and reduced cardiac function. Pediatric CAR studies examining cardiac toxicity are limited. We report on cardiac toxicity observed in children and young adults with hematologic malignancies enrolled in a CD19-28ζ CAR T-cell phase I trial (NCT01593696). All patients had a formal baseline echocardiogram. Real-time studies included echocardiograms on intensive care unit (ICU) transfer, and serial troponin and pro-B-type natriuretic peptide (pro-BNP) in the select patients. From July 2012 to March 2016, 52 patients, with a median age of 13.4 years (range 4.2-30.3) were treated. CRS developed in 37/52 (71%), which was grade 3-4 CRS in nine patients (17%). The median prior anthracycline exposure was 205 mg/m2 (range 70-620 mg/m2) in doxorubicin equivalents. The median baseline left ventricle ejection fraction (LVEF) and baseline LV global longitudinal strain (GLS) were 60% (range 50%-70%) and 16.8% (range 14.1%-23.5%, n=37) respectively. The majority, 78% (29/37), of patients had a reduced GLS <19% at baseline, and 6% (3/52) of patients had baseline LVEF <53%. ICU transfers occurred in 21 patients, with nine requiring vasoactive hemodynamic support and three necessitating >1 vasopressor. Six (12%) patients developed cardiac dysfunction (defined by >10% absolute decrease in LVEF or new-onset grade 2 or higher LV dysfunction, per CTCAE v4), among whom 4 had grade 3-4 CRS. Troponin elevations were seen in 4 of 13 patients, all of whom had low LVEF. Pro-BNP was elevated from baseline in 6/7 patients at the onset of CRS, with higher levels correlating with more severe CRS. Cardiac dysfunction fully resolved in all but two patients by day 28 post-CAR. Cardiac toxicity related to CD19-28ζ CAR T-cell-associated CRS was generally reversible by day 28 postinfusion. Implementation of more frequent monitoring with formal echocardiograms incorporating systemic analysis of changes in GLS, and cardiac biomarkers (troponin and proBNP) may help to earlier identify those patients at highest risk of severe cardiac systolic dysfunction, facilitating earlier interventions for CRS to potentially mitigate acute cardiac toxicity.

Dataset Information

EEG Correlates of Delirium in Children and Young Adults With CD19-Directed CAR T Cell Treatment-Related Neurotoxicity.

Introduction

Methods

Results

Conclusions

Publications

EEG Correlates of Delirium in Children and Young Adults With CD19-Directed CAR T Cell Treatment-Related Neurotoxicity.

Similar Datasets

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