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Journal of critical care · Jun 2020
Case ReportsExtracorporeal cytokine removal in severe CAR-T cell associated cytokine release syndrome.
- Klaus Stahl, Schmidt Bernhard M W BMW Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany. Electronic address: schmidt.bernhardt@mh-hannover.de., Marius M Hoeper, Thomas Skripuletz, Nora Möhn, Gernot Beutel, Matthias Eder, Tobias Welte, Arnold Ganser, Christine S Falk, Christian Koenecke, and Sascha David.
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: stahl.klaus@mh-hannover.de.
- J Crit Care. 2020 Jun 1; 57: 124-129.
PurposeLife-threatening complications of CD-19 Chimeric antigen receptor - T (CAR-T) cells such as the cytokine release syndrome (CRS)) have been reported. Treatment is limited to IL-6 blockade and steroids although global removal of elevated soluble inflammatory factors might be more effective.MethodsClinical course of a CRS patient treated with extracorporeal cytokine adsorption (Cytosorb®). A panel of 48 cytokines, chemokines and endothelial markers has been analyzed longitudinally. Ex vivo stimulation of endothelial cells to visualize (immunocytochemistry) and quantify (ECIS, TER) endothelial barrier effects.ResultsFollowing CAR-T cell application a 65 years old male developed grade 4 CRS with refractory shock (3 vasopressors) and severe capillary leakage (+37 L/24 h resuscitation). Treatment included IL-6 blockade, methylprednisolone and additionally Cytosorb hemoperfusion. While multiple soluble inflammatory factors were elevated and most of them decreased by more than 50% following Cytosorb, markers of endothelial injury increased steadily (e.g. Angpt-2/Angpt-1) leading to profound endothelial activation and leakage in ex vivo assays.ConclusionThis is the first reported use of cytokine adsorption for CRS showing efficacy in absorption of various cytokines but not endothelial growth factors. A randomized controlled trial to evaluate additional Cytosorb treatment in CRS is currently recruiting at our institution (NCT04048434).Copyright © 2020. Published by Elsevier Inc.
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