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Brain. 2019 May 1;142(5):1334-1348. doi: 10.1093/brain/awz053.

Neurological toxicities associated with chimeric antigen receptor T-cell therapy.

Author information

1
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
3
Department of Neurosurgery; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
4
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
5
Division of Nuclear Medicine, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
6
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
7
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Chimeric antigen receptor T cell therapy has become an important tool in the treatment of relapsed and refractory malignancy; however, it is associated with significant neurological toxicity. We characterized the neurological toxicity associated with chimeric antigen receptor T-cell therapy in a consecutive series of 100 patients up to 2 months post transfusion, 28 of whom were obtained from chart review and the others by prospective observation. The underlying neoplasms were lymphoma (74%), myeloma (14%), leukaemia (10%), and sarcoma (2%). The median age of the cohort was 64.5 years old and 39% of patients were female. The most commonly occurring neurological symptoms were encephalopathy (57%), headache (42%), tremor (38%), aphasia (35%) and focal weakness (11%). Focal neurological deficits are frequently observed after chimeric antigen receptor T-cell therapy and are associated with regional EEG abnormalities, FDG-PET hypometabolism, and elevated velocities on transcranial Doppler ultrasound. In contrast, structural imaging was typically normal. As this form of treatment is more widely adopted, recognition of the frequently encountered symptoms will be of increasing importance for the neurologists and oncologists caring for this growing patient population.

KEYWORDS:

CAR T cells; immunotherapy; neurotoxicity

PMID:
30891590
DOI:
10.1093/brain/awz053

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