Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 77, Issue 10, Pages 877-882Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnen/nly064
Keywords
Blood-brain barrier (BBB); Chimeric antigen receptor (CAR) T cells; Cerebral edema; Chimeric antigen receptor T cells; Cytokine release syndrome (CRS); Neurotoxicity
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Chimeric antigen receptor (CAR) T cells are a new and powerful class of cancer immunotherapeutics that have shown potential for the treatment of hematopoietic malignancies. The tremendous promise of this approach is tempered by safety concerns, including potentially fatal neurotoxicity, sometimes but not universally associated with cytokine release syndrome. We describe the postmortem examination of a brain from a 21-year-old patient with relapsed pre-B cell acute lymphoblastic leukemia (ALL) who died from fulminant cerebral edema following CAR T-cell infusion. We found a range of changes that included activation of microglia, expansion of perivascular spaces by proteinaceous exudate, and clasmatodendrosis-a beading of glial fibrillary acidic protein consistent with astrocyte injury. Notably, within the brain parenchyma, we identified only infrequent T cells and did not identify ALL cells or CAR T cells. The overall findings are nonspecific but raise the possibility of astrocyte and blood-brain barrier dysfunction as a potential etiology of fatal CAR T-cell neurotoxicity in this patient.
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