Multifocal Necrotizing Leukoencephalopathy With Preferential Microglia Toxicity in a Patient Treated With Chimeric Antigen Receptor T-Cells and Review of the Literature

Abstract

Abstract Neurotoxic side effects of traditional systemic chemotherapy are abundantly described. The introduction of newly developed biologic therapeutics and cellular immune effector therapies has expanded the spectrum of neurotoxicity. Multifocal necrotizing leukoencephalopathy (MNL) is a pathologic condition of unknown etiology that has been observed in patients after prolonged critical illness. We observed a case of MNL in a patient treated with extensive multimodal therapy including chimeric antigen receptor T cells. A month before death, MRI demonstrated signs of inflammation and developing edema in brainstem structures. At autopsy the abnormal MRI regions showed a wave-like loss of microglia with hemorrhagic MNL in regions closest to the brain surface. These findings reiterate the susceptibility of white matter to antineoplastic therapy and suggest new mechanisms of neurotoxicity when traditional chemotherapy is combined with biologic or cellular effector therapy.