title: Systemic inflammatory response syndrome after administration of unmodified T lymphocytes.
abstract: Systemic inflammatory response syndrome (SIRS) is a rare systemic inflammatory response associated with fever, tachycardia, profound hypotension, and respiratory distress, which has been reported in cancer patients receiving T cells genetically modified with chimeric antigen receptors to retarget their specificity to tumor-associated antigens. The syndrome usually occurs following significant in vivo expansion of the infused cells and has been associated with tumor destruction/lysis. Analysis of patient plasma has shown elevated cytokine levels, and resolution of symptoms has been reported after administration of steroids and/or antibodies (such as anti-tumor necrosis factor and anti-interleukin (IL)-6 receptor antibodies) that interfere with cytokine responses.To date, SIRS has not been reported in subjects receiving genetically unmodified T cells with native receptors directed against tumor antigens, in which greater physiological control of T-cell activation and expansion may occur. Here, however, we report a patient with bulky refractory Epstein-Barr virus (EBV)-associated lymphoma, who developed this syndrome 2 weeks after receiving T cells directed against EBV antigens through their native receptors. She was treated with steroids and etanercept, with rapid resolution of symptoms. SIRS may therefore occur even when T cells recognize antigens physiologically through their "wild-type" native receptors and should be acknowledged as a potential complication of this therapy.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Papadopoulou
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Krance
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Allen
authors.affiliation: Department of Nuclear Medicine, Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lee
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Brenner
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Leen
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Texas Children's Hospital, Houston, Texas, USA. Electronic address: hheslop@bcm.edu.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D000068800:Etanercept; D004854:Herpesvirus 4, Human / Q000276:immunology; D006689:Hodgkin Disease / Q000276:immunology* / Q000628:therapy / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007167:Immunotherapy / Q000009:adverse effects; D011241:Prednisone / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept; D011241:Prednisone