Quadriparesis and paraparesis following chimeric antigen receptor T-cell (CART) therapy in children and adolescents.
Caroline DiorioLaura Hernandez-MiyaresDiego A EspinozaBrenda BanwellAmit Bar-OrAmanda DiNofiaAllison Barz LeahyZachary MartinezRegina M MyersSarah E HopkinsSusan R RheingoldDavid Trent TeacheyAngela ViaeneLisa WrayShannon L MaudeStephan A GruppJennifer McGuirePublished in: Blood (2024)
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common but potentially severe adverse event associated with chimeric antigen receptor T-cell (CART) therapy characterized by the development of acute neurologic symptoms following CART infusion. ICANS encompasses a wide clinical spectrum typified by mild to severe encephalopathy, seizures and/or cerebral edema. As more patients have been treated with CART new ICANS phenomenology has emerged. We present the clinical course of five children who developed acute onset of quadriparesis or paraparesis associated with abnormal brain and/or spine neuroimaging after infusion of CD19 or CD22-directed CART, adverse events not previously reported in children. Orthogonal data from autopsy studies, cerebrospinal fluid (CSF) flow cytometry and CSF proteomics/cytokine profiling demonstrated chronic white matter destruction, but a notable lack of inflammatory pathologic changes and cell populations. Instead, children with quadriparesis or paraparesis post-CART therapy had lower levels of pro-inflammatory cytokines such as interferon gamma (IFN), CCL17, CCL23, and CXCL10 than those who did not develop quadriparesis or paraparesis. Taken together, these findings imply a non-inflammatory source of this newly described ICANS phenomenon in children. The pathophysiology of some neurologic symptoms following CART may therefore have a more complex etiology than exclusive T-cell activation and excessive cytokine production.
Keyphrases
- young adults
- white matter
- drug induced
- cerebrospinal fluid
- liver injury
- single cell
- flow cytometry
- cell therapy
- liver failure
- end stage renal disease
- newly diagnosed
- early onset
- low dose
- emergency department
- multiple sclerosis
- chronic kidney disease
- squamous cell carcinoma
- mass spectrometry
- prognostic factors
- intensive care unit
- neoadjuvant chemotherapy
- physical activity
- bone marrow
- resting state
- radiation therapy
- lymph node
- mesenchymal stem cells
- machine learning
- peritoneal dialysis
- extracorporeal membrane oxygenation
- locally advanced
- data analysis
- nk cells
- acute respiratory distress syndrome
- aortic dissection