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  1. Article ; Online: Toxicities associated with adoptive cellular therapies.

    Hansen, Doris K / Dam, Marian / Faramand, Rawan G

    Best practice & research. Clinical haematology

    2021  Volume 34, Issue 3, Page(s) 101287

    Abstract: Chimeric antigen receptor (CAR) T cell therapy is an effective strategy for the treatment of relapsed/refractory hematologic malignancies leading to the Food and Drug Administration (FDA) approval of five CAR T cell products. Despite encouraging efficacy, ...

    Abstract Chimeric antigen receptor (CAR) T cell therapy is an effective strategy for the treatment of relapsed/refractory hematologic malignancies leading to the Food and Drug Administration (FDA) approval of five CAR T cell products. Despite encouraging efficacy, the widespread utilization of CAR T cell therapy is limited by unique immune mediated toxicities, primarily cytokine release syndrome (CRS) and neurologic toxicity. Data regarding late effects and long-term toxicities of CAR T cell therapy is evolving and includes prolonged cytopenias, hypogammaglobulinemia, infections and secondary malignancies. In this review, we will describe the clinical presentation, diagnosis, mechanisms and management of short- and long-term toxicities of CAR T cell therapy.
    MeSH term(s) Disease Progression ; Hematologic Neoplasms/therapy ; Humans ; Immunotherapy, Adoptive ; Neoplasm Recurrence, Local ; T-Lymphocytes
    Language English
    Publishing date 2021-07-24
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2048027-1
    ISSN 1532-1924 ; 1521-6926
    ISSN (online) 1532-1924
    ISSN 1521-6926
    DOI 10.1016/j.beha.2021.101287
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Se 1029: Show issues Location:
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  2. Article ; Online: Baseline Serum Inflammatory Proteins Predict Poor CAR T Outcomes in Diffuse Large B-cell Lymphoma.

    Faramand, Rawan G / Lee, Sae Bom / Jain, Michael D / Cao, Biwei / Wang, Xuefeng / Rejeski, Kai / Subklewe, Marion / Fahrmann, Johannes F / Saini, Neeraj Y / Hanash, Samir M / Kang, Yun Pyo / Chang, Darwin / Rodriguez, Paolo C / Dean, Erin A / Nishihori, Taiga / Shah, Bijal D / Lazaryan, Aleksandr / Chavez, Julio / Khimani, Farhad /
    Pinilla-Ibarz, Javier A / Dam, Marian / Reid, Kayla M / Corallo, Salvatore A / Menges, Meghan / Hidalgo Vargas, Melanie / Mandula, Jay K / Holliday, Brian A / Bachmeier, Christina A / Speth, Kelly / Song, Qinghua / Mattie, Mike / Locke, Frederick L / Davila, Marco L

    Blood cancer discovery

    2024  Volume 5, Issue 2, Page(s) 106–113

    Abstract: A subset of patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 chimeric antigen receptor (CAR) T-cell therapy have poor clinical outcomes. We report serum proteins associated with severe immune-mediated toxicities and inferior clinical ...

    Abstract A subset of patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 chimeric antigen receptor (CAR) T-cell therapy have poor clinical outcomes. We report serum proteins associated with severe immune-mediated toxicities and inferior clinical responses in 146 patients with DLBCL treated with axicabtagene ciloleucel. We develop a simple stratification based on pre-lymphodepletion C reactive protein (CRP) and ferritin to classify patients into low-, intermediate-, and high-risk groups. We observe that patients in the high-risk category were more likely to develop grade ≥3 toxicities and had inferior overall and progression-free survival. We sought to validate our findings with two independent international cohorts demonstrating that patients classified as low-risk have excellent efficacy and safety outcomes. Based on routine and readily available laboratory tests that can be obtained prior to lymphodepleting chemotherapy, this simple risk stratification can inform patient selection for CAR T-cell therapy.
    Significance: CAR T-cell therapy has changed the treatment paradigm for patients with relapsed/refractory hematologic malignancies. Despite encouraging efficacy, a subset of patients have poor clinical outcomes. We show that a simple clinically applicable model using pre-lymphodepletion CRP and ferritin can identify patients at high risk of poor outcomes. This article is featured in Selected Articles from This Issue, p. 80.
    MeSH term(s) Humans ; Receptors, Chimeric Antigen/therapeutic use ; Lymphoma, Large B-Cell, Diffuse/therapy ; Adaptor Proteins, Signal Transducing ; Antigens, CD19/therapeutic use ; Blood Proteins ; C-Reactive Protein ; Ferritins ; Hematologic Neoplasms
    Chemical Substances Receptors, Chimeric Antigen ; Adaptor Proteins, Signal Transducing ; Antigens, CD19 ; Blood Proteins ; C-Reactive Protein (9007-41-4) ; Ferritins (9007-73-2)
    Language English
    Publishing date 2024-01-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3028898-8
    ISSN 2643-3249 ; 2643-3230
    ISSN (online) 2643-3249
    ISSN 2643-3230
    DOI 10.1158/2643-3230.BCD-23-0056
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel.

    Faramand, Rawan / Jain, Michael / Staedtke, Verena / Kotani, Hiroshi / Bai, Renyuan / Reid, Kayla / Lee, Sae Bom / Spitler, Kristen / Wang, Xuefeng / Cao, Biwei / Pinilla, Javier / Lazaryan, Aleksander / Khimani, Farhad / Shah, Bijal / Chavez, Julio C / Nishihori, Taiga / Mishra, Asmita / Mullinax, John / Gonzalez, Ricardo /
    Hussaini, Mohammad / Dam, Marian / Brandjes, Brigett D / Bachmeier, Christina A / Anasetti, Claudio / Locke, Frederick L / Davila, Marco L

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2020  Volume 26, Issue 18, Page(s) 4823–4831

    Abstract: Purpose: One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity ...

    Abstract Purpose: One of the challenges of adoptive T-cell therapy is the development of immune-mediated toxicities including cytokine release syndrome (CRS) and neurotoxicity (NT). We aimed to identify factors that place patients at high risk of severe toxicity or treatment-related death in a cohort of 75 patients with large B-cell lymphoma treated with a standard of care CD19 targeted CAR T-cell product (axicabtagene ciloleucel).
    Experimental design: Serum cytokine and catecholamine levels were measured prior to lymphodepleting chemotherapy, on the day of CAR T infusion and daily thereafter while patients remained hospitalized. Tumor biopsies were taken within 1 month prior to CAR T infusion for evaluation of gene expression.
    Results: We identified an association between pretreatment levels of IL6 and life-threatening CRS and NT. Because the risk of toxicity was related to pretreatment factors, we hypothesized that the tumor microenvironment (TME) may influence CAR T-cell toxicity. In pretreatment patient tumor biopsies, gene expression of myeloid markers was associated with higher toxicity.
    Conclusions: These results suggest that a proinflammatory state and an unfavorable TME preemptively put patients at risk for toxicity after CAR T-cell therapy. Tailoring toxicity management strategies to patient risk may reduce morbidity and mortality.
    MeSH term(s) Adult ; Aged ; Biological Products/adverse effects ; Biopsy ; Cytokine Release Syndrome/chemically induced ; Cytokine Release Syndrome/epidemiology ; Cytokine Release Syndrome/immunology ; Female ; Humans ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Lymphoma, Large B-Cell, Diffuse/immunology ; Lymphoma, Large B-Cell, Diffuse/therapy ; Male ; Middle Aged ; Receptors, Chimeric Antigen/immunology ; Risk Factors ; Tumor Microenvironment/immunology ; Young Adult
    Chemical Substances Biological Products ; Receptors, Chimeric Antigen ; axicabtagene ciloleucel (U2I8T43Y7R)
    Language English
    Publishing date 2020-07-15
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-20-1434
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4223: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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