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Cytokine release syndrome

About: Cytokine release syndrome is a(n) research topic. Over the lifetime, 1288 publication(s) have been published within this topic receiving 56478 citation(s). The topic is also known as: CRS & CSS.

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Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30628-0
Puja Mehta1, Daniel F. McAuley2, Michael Brown3, Emilie Sanchez3  +3 moreInstitutions (5)
28 Mar 2020-The Lancet
Abstract: www.thelancet.com Published online March 13, 2020 https://doi.org/10.1016/S0140-6736(20)30628-0 1 Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/ However, in hyperinflammation, immunosuppression is likely to be beneficial. Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events. A multicentre, randomised con trolled trial of tocilizumab (IL-6 receptor blockade, licensed for cytokine release syndrome), has been approved in patients with COVID-19: consider cytokine storm syndromes and immunosuppression

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5,489 Citations


Open accessJournal ArticleDOI: 10.1016/S0140-6736(14)61403-3
07 Feb 2015-The Lancet
Abstract: Summary Background Chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown activity in case series of patients with acute and chronic lymphocytic leukaemia and B-cell lymphomas, but feasibility, toxicity, and response rates of consecutively enrolled patients treated with a consistent regimen and assessed on an intention-to-treat basis have not been reported. We aimed to define feasibility, toxicity, maximum tolerated dose, response rate, and biological correlates of response in children and young adults with refractory B-cell malignancies treated with CD19-CAR T cells. Methods This phase 1, dose-escalation trial consecutively enrolled children and young adults (aged 1–30 years) with relapsed or refractory acute lymphoblastic leukaemia or non-Hodgkin lymphoma. Autologous T cells were engineered via an 11-day manufacturing process to express a CD19-CAR incorporating an anti-CD19 single-chain variable fragment plus TCR zeta and CD28 signalling domains. All patients received fludarabine and cyclophosphamide before a single infusion of CD19-CAR T cells. Using a standard 3 + 3 design to establish the maximum tolerated dose, patients received either 1 × 10 6 CAR-transduced T cells per kg (dose 1), 3 × 10 6 CAR-transduced T cells per kg (dose 2), or the entire CAR T-cell product if sufficient numbers of cells to meet the assigned dose were not generated. After the dose-escalation phase, an expansion cohort was treated at the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT01593696. Findings Between July 2, 2012, and June 20, 2014, 21 patients (including eight who had previously undergone allogeneic haematopoietic stem-cell transplantation) were enrolled and infused with CD19-CAR T cells. 19 received the prescribed dose of CD19-CAR T cells, whereas the assigned dose concentration could not be generated for two patients (90% feasible). All patients enrolled were assessed for response. The maximum tolerated dose was defined as 1 × 10 6 CD19-CAR T cells per kg. All toxicities were fully reversible, with the most severe being grade 4 cytokine release syndrome that occurred in three (14%) of 21 patients (95% CI 3·0–36·3). The most common non-haematological grade 3 adverse events were fever (nine [43%] of 21 patients), hypokalaemia (nine [43%] of 21 patients), fever and neutropenia (eight [38%] of 21 patients), and cytokine release syndrome (three [14%) of 21 patients). Interpretation CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia. All toxicities were reversible and prolonged B-cell aplasia did not occur. Funding National Institutes of Health Intramural funds and St Baldrick's Foundation.

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Topics: T cell (57%), Chimeric Antigen Receptor T-Cell Therapy (53%), Cytokine release syndrome (53%) ...read more

1,964 Citations


Open accessJournal ArticleDOI: 10.1126/SCITRANSLMED.3008226
Marco L. Davila1, Isabelle Riviere, Xiuyan Wang1, Shirley Bartido1  +28 moreInstitutions (2)
Abstract: We report on 16 patients with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL) that we treated with autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. The overall complete response rate was 88%, which allowed us to transition most of these patients to a standard-of-care allogeneic hematopoietic stem cell transplant (allo-SCT). This therapy was as effective in high-risk patients with Philadelphia chromosome-positive (Ph(+)) disease as in those with relapsed disease after previous allo-SCT. Through systematic analysis of clinical data and serum cytokine levels over the first 21 days after T cell infusion, we have defined diagnostic criteria for a severe cytokine release syndrome (sCRS), with the goal of better identifying the subset of patients who will likely require therapeutic intervention with corticosteroids or interleukin-6 receptor blockade to curb the sCRS. Additionally, we found that serum C-reactive protein, a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS. Together, our data provide strong support for conducting a multicenter phase 2 study to further evaluate 19-28z CAR T cells in B-ALL and a road map for patient management at centers now contemplating the use of CAR T cell therapy.

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1,787 Citations


Open accessJournal ArticleDOI: 10.1182/BLOOD-2014-05-552729
10 Jul 2014-Blood
Abstract: As immune-based therapies for cancer become potent, more effective, and more widely available, optimal management of their unique toxicities becomes increasingly important. Cytokine release syndrome (CRS) is a potentially life-threatening toxicity that has been observed following administration of natural and bispecific antibodies and, more recently, following adoptive T-cell therapies for cancer. CRS is associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon γ, and uncontrolled studies demonstrate that immunosuppression using tocilizumab, an anti-IL-6 receptor antibody, with or without corticosteroids, can reverse the syndrome. However, because early and aggressive immunosuppression could limit the efficacy of the immunotherapy, current approaches seek to limit administration of immunosuppressive therapy to patients at risk for life-threatening consequences of the syndrome. This report presents a novel system to grade the severity of CRS in individual patients and a treatment algorithm for management of CRS based on severity. The goal of our approach is to maximize the chance for therapeutic benefit from the immunotherapy while minimizing the risk for life threatening complications of CRS.

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Topics: Cytokine release syndrome (55%), Tocilizumab (53%), Immunotherapy (52%) ...read more

1,537 Citations


Open accessJournal ArticleDOI: 10.1016/J.JINF.2020.03.037
Qing Ye1, Bili Wang1, Jianhua Mao1Institutions (1)
Abstract: Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.

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1,409 Citations


Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20221
2021405
2020319
2019154
2018106
201761

Top Attributes

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Topic's top 5 most impactful authors

Stephan A. Grupp

28 papers, 5.7K citations

Cameron J. Turtle

24 papers, 4.9K citations

Carl H. June

22 papers, 2.9K citations

Bruce L. Levine

15 papers, 1.6K citations

Simon F. Lacey

13 papers, 2.2K citations

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