Research Article: Viable CAR T-cells remain detectable in cerebrospinal fluid in patients with grade ?3 ICANS despite corticosteroid therapy
Abstract:
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a severe complication of CAR T-cell therapy. Although CAR T-cells have been detected in cerebrospinal fluid (CSF), their viability remains unknown.
We retrospectively analyzed all patients with grade ?3 ICANS after commercial CAR T-cell therapy (February 2022 – September 2025) who underwent lumbar puncture (n=13). CSF was analyzed by flow cytometry including 7-AAD staining for CAR T-cell viability. Viable CAR T-cells were defined as CAR + CD3 + 7-AAD ? lymphocytes. A systematic literature review identified published cases with CSF CAR T-cell detection.
Among 133 CAR T-cell recipients, 28 developed grade ?3 ICANS and 13 underwent lumbar puncture (total 22 samples). Viability testing was feasible in 11 samples; all contained viable CAR T-cells (median 75%, range 27–99%), which remained detectable up to day +98 despite corticosteroid therapy. Median CSF CAR T-cell count was 4.3/µL (IQR 1.7–18.1). Protein and albumin were elevated in most patients, indicating blood–CSF barrier disruption. A literature review identified 17 published cases reporting CSF findings after CAR T-cell therapy.
To our knowledge, this is the first study demonstrating that CAR T-cells in the CSF are viable and remain detectable despite corticosteroid therapy. These findings demonstrate the presence of viable CAR T cells in the CSF of patients with ICANS and warrant prospective functional studies.
Introduction:
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a severe complication of CAR T-cell therapy. Although CAR T-cells have been detected in cerebrospinal fluid (CSF), their viability remains unknown.
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