Presented at: Oncology Nursing Society 40th Annual Congress; April 22-26, 2015; Orlando, FL. [theoncologynurse.com]

Neurotoxicity, presenting as headache, altered mental status, delirium, aphasia, hallucinations, or seizures, is now often considered an event separate from CRS, he said. [mdedge.com]

Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T-cells [published online February 26, 2019]. [cancertherapyadvisor.com]

Fc receptors present on the surface of antibody opsonised target cells bind with Fc region of antibody followed by signal transduction and massive release of cytokines. Drugs like rituximab and alemtuzumab act via this mechanism. [microbiologyjournal.org]

Case Presentation: A 43-year-old male with advanced gastric cancer was treated with nivolumab as a third-line chemotherapy. He had no history of allergies. [karger.com]

• Hypoxemia

  CRS causes various symptoms, such as fever, hypotension, hypoxemia, tachycardia, liver injury and neurological disorders. [karger.com]

  Perform tests before initiation of CAR-T-cell therapy if infection suspected Delay CAR-T cell therapy until infection has been controlled/ruled out Cardiovascular Tachycardia/hypotension Capillary leak Cardiac dysfunction Respiratory Tachypnea, hypoxemia [pepidconnect.com]

  Subsequent Events After an initial recovery, Patient 6 became hypotensive (blood pressure, 65/40 mm Hg), and 12 hours after infusion, he had metabolic acidosis and marked respiratory distress with hypoxemia that was refractory to treatment with supplemental [nejm.org]

• Renal Injury

  Electrolyte imbalances, azotemia, renal injury due to reduced renal perfusion [11,15] Nervous Headache, confusion, hallucination, dysphasia, tremor, seizure, facial nerve palsy, altered gait [8] Musculoskeletal Elevated creatine kinase, myalgias, weakness [microbiologyjournal.org]

• Lymphopenia

  In particular, the severe lymphopenia observed in these patients was unexpected; a temporary lymphocytosis had been observed in preclinical studies of TGN1412 in animals. 3,4,14 This unanticipated lymphopenia in humans may have reflected cell death or [nejm.org]

  Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. [scielo.cl]

  Table (1): Symptoms associated with CRS and sites of body affected Organ systems affected Symptoms Constitutional Fever, headache, anorexia, malaise, myalgias, rigors [11, 12] Integument Skin rashes [11] Blood Cytopenias (anaemia, leucopenia, lymphopenia [microbiologyjournal.org]

• Cytopenia

  Prolonged Cytopenias: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and KYMRIAH infusion. [hcp.novartis.com]

  HLH is a rare immune disorder characterized by cytopenias, prolonged fever, hyperferritinemia, hypertriglyceridemia, spleenomegaly, coagulopathy, decreased efficacy of natural killer cells and elevation in cytokine level 36. [microbiologyjournal.org]

It confirms that Actemra® does have treatment effect on such symptom. [creative-biolabs.com]

Actemra is the first approved treatment for CRS in this setting. In Japan, Actemra is also approved for the treatment of Castleman’s Disease and Takayasu Arteritis. [roche.com]

Improved therapeutic and preventive treatments require a better understanding of CRS physiopathology, which has so far remained elusive. [e-cancer.fr]

Children and young people may be able to travel to England for treatment. This treatment has not been approved in Scotland for adults with lymphoma. [about-cancer.cancerresearchuk.org]

CytoSorb ® has been used in more than 67,000 human treatments to date. [cytosorbents.com]

The ultimate goal is to avoid grade 4 CRS, he said, which involves grade 4 organ toxicity, requires mechanical ventilation, and yields a poor prognosis despite vigilant supportive care, tocilizumab, and corticosteroids. Dr. [mdedge.com]

T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J. Clin. Oncol. 36(22), 2267–2280 ( 2018 ). Crossref, Medline, CAS, Google Scholar 16. [futuremedicine.com]

Major efforts are ongoing to characterize the pathogenesis and etiology of CRS and CRES. Mouse models have been established to… CONTINUE READING [semanticscholar.org]

[…] levels to baseline CRES : biphasic manifestation of toxic encephalopathy Mechanism yet to be determined; 2 postulates Passive diffusion of cytokines into the brain (e.g., IL-6, IL-15) Migration of T-cells into the CNS (detection of CAR-T cells in CSF) Etiology [pepidconnect.com]

CRS and guide dosing for Phase I trials, and regulatory agencies expect to see results of such tests in investigational new drug applications. [4] [10] A modified chandler loop model can be used as a preclinical tool to assess infusion reactions. [1] Epidemiology [en.wikipedia.org]

T-cells into the CNS (detection of CAR-T cells in CSF) Etiology/Risk Factors CRS has classically been associated with Therapeutic mAb infusions Most notably anti-CD3 (OKT3) Anti-CD52 (alemtuzumab) 19 anti-CD20 (rituximab) CD28 super-agonist, TGN1412 Epidemiology [pepidconnect.com]

Macrophage activation syndrome in adults: recent advances in pathophysiology, diagnosis and treatment. [scielo.cl]

Neurotoxicity: temporal & pathophysiological relationship with CRS Neurotoxicity is a life-threatening complication associated with CAR T cells and BiTEs. [futuremedicine.com]

CAR-T-cell-related encephalopathy syndrome (CRES) Fulminant CRS may be life-threatening CRS can evolve into fulminant hemophagocytic lymphohistiocytosis (HLH) Also known as macrophage-activation syndrome (MAS) Management of CRS and CRES can be life saving Pathophysiology [pepidconnect.com]

Earlier seems to be better, although we do not yet know if prophylactic tocilizumab or corticosteroids can prevent CRS symptoms before they start.” For hypotensive patients on pressors, Dr. [mdedge.com]

Management Monitoring and aggressive supportive care should be considered in order to prevent irreversible end-organ damage. Consider ICU setting (1:1 nursing care). Consider involving expert consultative services. [mdcalc.com]

Recently, considerable developments have been achieved with regard to the prevention or control of this syndrome. In this review it is aimed to summarize the clinical approach to cytokine release syndrome and associated conditions. [journalofoncology.org]

It binds to the IL-6 receptor, preventing IL-6 from activating end-stage cells or endothelial cells, inflammatory cells, and a variety of things that can be upregulated in terms of inflammation by IL-6. [managingmyeloma.com]

Improved therapeutic and preventive treatments require a better understanding of CRS physiopathology, which has so far remained elusive. [e-cancer.fr]