Klaus Stahl1, Bernhard M W Schmidt2, Marius M Hoeper3, Thomas Skripuletz4, Nora Möhn5, Gernot Beutel6, Matthias Eder7, Tobias Welte8, Arnold Ganser9, Christine S Falk10, Christian Koenecke11, Sascha David12. 1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: stahl.klaus@mh-hannover.de. 2. Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany. Electronic address: schmidt.bernhardt@mh-hannover.de. 3. Department of Respiratory Medicine and German Centre of Lung Research (DZL), Hannover Medical School, Hannover, Germany. Electronic address: hoeper.marius@mh-hannover.de. 4. Department of Neurology, Hannover Medical School, Hannover, Germany. Electronic address: skripuletz.thomas@mh-hannover.de. 5. Department of Neurology, Hannover Medical School, Hannover, Germany. Electronic address: moehn.nora@mh-hannover.de. 6. Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany. Electronic address: beutel.gernot@mh-hannover.de. 7. Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany. Electronic address: eder.matthias@mh-hannover.de. 8. Department of Respiratory Medicine and German Centre of Lung Research (DZL), Hannover Medical School, Hannover, Germany. Electronic address: welte.tobias@mh-hannover.de. 9. Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany. Electronic address: ganser.arnold@mh-hannover.de. 10. Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany. Electronic address: falk.christine@mh-hannover.de. 11. Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany. Electronic address: koenecke.christian@mh-hannover.de. 12. Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany. Electronic address: david.sascha@mh-hannover.de.
Abstract
PURPOSE: Life-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. METHODS: Clinical 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. RESULTS: Following 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. CONCLUSION: This 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).
PURPOSE: Life-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. METHODS: Clinical course of a CRSpatient 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. RESULTS: Following 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. CONCLUSION: This 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).
Authors: Nora Möhn; Viktoria Bonda; Lea Grote-Levi; Victoria Panagiota; Tabea Fröhlich; Christian Schultze-Florey; Mike P Wattjes; Gernot Beutel; Matthias Eder; Sascha David; Sonja Körner; Günter Höglinger; Martin Stangel; Arnold Ganser; Christian Koenecke; Thomas Skripuletz Journal: Neurol Res Pract Date: 2022-01-10
Authors: Christina Scharf; Ines Schroeder; Michael Paal; Martin Winkels; Michael Irlbeck; Michael Zoller; Uwe Liebchen Journal: Ann Intensive Care Date: 2021-07-22 Impact factor: 6.925