{"doi":"10.1093/neuonc/noac034","title":"Neurotoxicity following CD19/CD28ζ CAR T-cells in children and young adults with B-cell malignancies","abstract":"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. Patients with active CNS leukemia were included. RESULTS: Amongst 52 patients treated, 13 patients had active CNS leukemia at infusion. Neurotoxicity was seen in 11/52 (21.2%) patients, with an incidence of 29.7% (11/37) in patients with CRS. Neurotoxicity was associated with the presence and severity of CRS. Those with neurotoxicity had higher levels of peak serum IL-6, IFNγ, and IL-15. Additionally, CNS leukemia was effectively eradicated in most patients with CRS. Pilot neurocognitive testing demonstrated stable-to-improved neurocognitive test scores in most patients, albeit limited by small patient numbers. The NSC enabled caregiver input into the patient experience. CONCLUSIONS: This is the first systematic analysis of neurotoxicity utilizing a CD19/CD28ζ CAR construct in CAYA, including in those with active CNS involvement. The experience demonstrates that the neurotoxicity profile was acceptable and reversible, with evidence of anti-leukemia response and CNS trafficking of CAR T-cells. Additionally, neurocognitive testing, while exploratory, provides an opportunity for future studies to employ systematic evaluations into neurotoxicity assessments and validation is needed in future studies.","journal":"Neuro-Oncology","year":2022,"id":243737,"datarank":0.9848655256817853,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.46038939146181324,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.46038939146181324,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":24,"citers_with_citation_signal":17,"citers_with_endowment":17,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9405,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01593696"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":109189,"name":"Staci Martin","orcid":"0000-0002-9342-4173","position":1,"is_corresponding":false},{"id":283310,"name":"Bonnie Yates","orcid":null,"position":2,"is_corresponding":false},{"id":109180,"name":"Pamela L. Wolters","orcid":"0000-0001-9319-6281","position":3,"is_corresponding":false},{"id":876257,"name":"Claire M. Kaplan","orcid":"0000-0003-2753-8225","position":4,"is_corresponding":false},{"id":876258,"name":"Hannah Smith","orcid":"0000-0002-7966-2538","position":5,"is_corresponding":false},{"id":876823,"name":"Christopher R Sesi","orcid":null,"position":6,"is_corresponding":false},{"id":876824,"name":"Jennifer Jess","orcid":null,"position":7,"is_corresponding":false},{"id":448365,"name":"Mary Anne Toledo‐Tamula","orcid":null,"position":8,"is_corresponding":false},{"id":447406,"name":"Kari Struemph","orcid":"0000-0003-4148-7911","position":9,"is_corresponding":false},{"id":283313,"name":"Cindy Delbrook","orcid":null,"position":10,"is_corresponding":false},{"id":876259,"name":"Omar Khan","orcid":"0000-0003-2879-8790","position":11,"is_corresponding":false},{"id":225351,"name":"Crystal L. Mackall","orcid":"0000-0003-0359-9023","position":12,"is_corresponding":false},{"id":283314,"name":"Daniel W Lee","orcid":null,"position":13,"is_corresponding":false},{"id":280941,"name":"Nirali N. Shah","orcid":"0000-0002-8474-9080","position":14,"is_corresponding":false},{"id":280937,"name":"Haneen Shalabi","orcid":"0000-0001-8692-8034","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T00:23:20.901576Z","pmid":"35148417","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}