12 results on '"*CYTOKINE release syndrome"'
Search Results
2. Current development of chimeric antigen receptor T‐cell therapy for diffuse large B‐cell lymphoma and high‐grade B‐cell lymphoma.
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Yamauchi, Nobuhiko and Maruyama, Dai
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DIFFUSE large B-cell lymphomas , *CHIMERIC antigen receptors , *T cells , *LYMPHOMAS - Abstract
Chimeric antigen receptor (CAR) T‐cell therapy has become a commercially available treatment option for relapsed or refractory (r/r) diffuse large B‐cell lymphoma (DLBCL) with two or more lines of prior therapies, and recently for high‐risk r/r DLBCL with one prior line of therapy. The successful development of CAR T‐cell therapy for multiple relapsed DLBCL has led to a boom in subsequent trials that investigated its utility in patients with other r/r B‐cell lymphoma subtypes. However, CAR T‐cell therapy is a multistep process that includes leukapheresis and manipulation which take several weeks. Therefore, patients with rapidly progressing or bulky disease may not be able to complete the therapeutic regimen involving CAR T‐cell products. This raises the question of the generalizability of the results of pivotal studies to the entire population. In this review, we summarize the development of CAR‐T cell therapy for B‐cell lymphoma and discuss strategies to further improve the clinical outcomes of this treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Application of thromboelastography to predict the severity of bleeding after chimeric antigen receptor (CAR)‐T cell therapy in patients with hematological malignancy.
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Chen, Liu, Ding, Shuyi, Cheng, Yin, Zhou, Linghui, Yan, Jiali, Cheng, Qiong, Jin, Aiyun, Zhou, Xiaoyu, Huang, He, and Hu, Yongxian
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CHIMERIC antigen receptors , *HEMATOLOGIC malignancies , *CELLULAR therapy , *THROMBELASTOGRAPHY , *CYTOKINE release syndrome , *PROPOFOL infusion syndrome - Abstract
Objectives: We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)‐T cell therapy. Methods: A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non‐severe bleeding group. The thromboelastography data was collected on the day of CAR‐T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR‐T cell infusion. Results: The patients of the severe bleeding group had lower platelet (p <.007), maximum amplitude (p =.002), coagulation index (p =.005), and longer coagulation time (p =.019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0–10, opposite on Days 10–20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR‐T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84–0.95; p <.001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35–5.32; p =.006) were significantly associated with high bleeding severity. Conclusions: Thromboelastography was considered to be a good predictor of bleeding severity. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Long‐term survivorship care after CAR‐T cell therapy.
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Puckrin, Robert, Jamani, Kareem, and Jimenez‐Zepeda, Victor H.
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CELLULAR therapy , *IMMUNE reconstitution inflammatory syndrome , *CYTOKINE release syndrome , *LONG-term health care , *CHIMERIC antigen receptors , *PSYCHOLOGICAL distress - Abstract
While cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome are well‐recognized acute toxicities of chimeric antigen receptor (CAR) T cell therapy, these complications have become increasingly manageable by protocolized treatment algorithms incorporating the early administration of tocilizumab and corticosteroids. As CAR‐T cell therapy expands to new disease indications and the number of long‐term survivors steadily increases, there is growing recognition of the need to appropriately evaluate and manage the late effects of CAR‐T cell therapy, including late‐onset or persistent neurotoxicity, prolonged cytopenias, delayed immune reconstitution and infections, subsequent malignancies, organ dysfunction, psychological distress, and fertility implications. In this review, we provide a practical approach to the long‐term survivorship care of the CAR‐T cell recipient, with a focus on the optimal strategies to address the common and challenging late complications affecting this unique population. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Donor‐derived stem cell infusion for sustained pancytopenia after CD19 CAR‐T therapy for relapsed patients post allogeneic stem cell transplantation.
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Li, Yingying, Li, Yixue, Zhang, Mingming, Zhao, Houli, Zhu, Miaoyong, Huang, He, and Hu, Yongxian
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STEM cell transplantation , *HEMATOPOIETIC stem cell transplantation , *STEM cells , *CYTOKINE release syndrome , *CD19 antigen , *PANCYTOPENIA - Abstract
Objectives: To investigate the effectiveness of donor‐derived chimeric antigen receptor T (CAR‐T) cells in the treatment of relapsed cases after allogeneic hematopoietic stem cell transplantation (allo‐HSCT), and whether donor‐derived peripheral blood stem cells (PBSCs) have a therapeutic effect on pancytopenia after CAR‐T cell therapy. Methods: We analyzed data from five adults with B‐cell acute lymphoblastic leukemia (ALL) who had relapse after allo‐HSCT and received donor‐derived CAR‐T cell therapy and donor‐derived PBSCs to promote hematopoietic recovery. Results: All patients had negative minimal residual disease after CAR‐T therapy, grade 1–2 cytokine release syndrome, and developed grade 4 hematologic toxicity. During the pancytopenia stage after CAR‐T cell therapy, donor‐derived PBSCs were transfused without graft‐versus‐host disease (GVHD) prophylaxis. Four patients had grade I–II acute GVHD (aGVHD). After corticosteroid treatment, aGVHD resolved and hematopoiesis was restored. Although steroids in combination with etanercept and ruxolitinib relieved symptoms in one patient with grade IV aGVHD, complete hematopoietic recovery was not achieved, and the patient died due to severe infection. Conclusions: Donor‐derived CAR‐T cell therapy is safe and effective in patients with relapsed/refractory ALL after allo‐HSCT. Donor‐derived PBSCs infusion could achieve hematopoietic recovery with controllable aGVHD in patients with persistent pancytopenia. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Characteristics and recognition of early infections in patients treated with commercial anti‐CD19 CAR‐T cells.
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Beyar‐Katz, Ofrat, Kikozashvili, Nino, Bar On, Yael, Amit, Odelia, Perry, Chava, Avivi, Irit, Gold, Ronit, Herishanu, Yair, Benyamini, Noam, Duek, Adrian, Ben‐Ami, Ronen, Shasha, David, and Ram, Ron
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DIFFUSE large B-cell lymphomas , *INFECTION , *CYTOKINE release syndrome , *BACTERIAL diseases , *CHIMERIC antigen receptors , *OLDER patients - Abstract
The characteristics of infections following chimeric antigen receptor T (CAR‐T) cells targeting CD19 in real‐word population are obscure. We analyzed infections' characteristics in the first month among consecutive patients with diffuse large B‐cell lymphoma (DLBCL) (n = 60, median age, 69.3 years), treated with commercial CAR‐T cells. ECOG performance status (PS) was 2‐3 in most patients (58%). Infections were observed in 45% of patients (16, 27%, bacterial infections, and 14, 23%, viral infections). Bacterial infection included clinically documented infection in 7 (Pneumonia, n = 5; periodontal infection, n = 1; and cellulitis, n = 1) and microbiology documented infection (MDI) in 9 patients (Gram‐negative rod, n = 5; Gram‐positive cocci, n = 3, bacteremia; polymicrobial, n = 1). The most common viral infection was cytomegalovirus (CMV) reactivation (n = 10, 17%) leading to initiation of anti‐CMV treatment in 6 (60%) among these patients. None had CMV disease. In univariate analysis, immune effector cell‐associated neurotoxicity syndrome (ICANS) was associated with higher incidence of bacterial infection (OR=4.5, P =.018), while there was a trend for lower incidence of bacterial infections in patients with chemosensitive disease to bridging therapy (OR=0.375, P =.074). Age or PS was not associated with increased risk of bacterial infection. Increase in C‐reactive protein (CRP) prior to fever onset was associated with microbiologically documented infections. We conclude that infections are common in the first month following CAR‐T‐cell administration, however, were not increased in elderly patients or those presenting with poorer PS. Increase in CRP prior to fever onset could support infection over cytokine release syndrome. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Impact of hypoalbuminemia on the prognosis of relapsed/refractory B‐cell lymphoma treated with axicabtagene ciloleucel.
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Melody, Megan, Gandhi, Sangeetha, Rahman, Zaid Abdel, Lengerke‐Diaz, Paula, Gannon, Nicole, Rosenthal, Allison, Truong, Tuan, Novo, Mattia, Brandes, Eva, Lange, Gina, Estby, Breana, Johnston, Patrick, Ansell, Steve, Bennani, N. Nora, Paludo, Jonas, Bisneto, Jose Villasboas, Ayala, Ernesto, Tun, Han W., Murthy, Hemant S., and Roy, Vivek
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DIFFUSE large B-cell lymphomas , *PROGNOSIS , *CYTOKINE release syndrome , *SERUM albumin , *LYMPHOMAS - Abstract
Introduction: Hypoalbuminemia is a known adverse prognostic factor in lymphomas. Yet, it is unknown if axicabtagene ciloleucel (axi‐cel) overcomes the adverse prognostic impact of hypoalbuminemia in relapsed/refractory large B‐cell lymphoma. Methods: We conducted a retrospective analysis across three Mayo Clinic centers to assess the relationship of hypoalbuminemia (defined as a serum albumin (SA) levels ≤ 3.5 g/dL) on outcomes of patients treated with axi‐cel. Results: This analysis included 81 patients. Two patients had no available SA levels preceding axi‐cel infusion. Eighteen patients (22.8%) had hypoalbuminemia with a median SA of 3.3 g/dL. Patients with normal SA had a statistically higher ORR than those without hypoalbuminemia (P =.018). There was no difference in 1‐year PFS and OS between the group with hypoalbuminemia and the group with normal SA levels (48% vs 49%, P =.81) and (74% vs 73%, P =.97), respectively. There was no difference in the severity or median duration of cytokine release syndrome or neurotoxicity between the two groups. Conclusion: Notwithstanding the limitations related to the relatively small sample size, axi‐cel therapy appears to overcome the adverse effect of hypoalbuminemia on OS and PFS. Large multicenter clinical studies are certainly needed to validate these findings. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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8. Cytokine gene polymorphisms are associated with response to blinatumomab in B‐cell acute lymphoblastic leukemia.
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Jeyakumar, Nikeshan, Aldoss, Ibrahim, Yang, Dongyun, Mokhtari, Sally, Gendzekhadze, Ketevan, Khaled, Samer, O'Donnell, Margaret, Palmer, Joycelynne, Song, Joo Y., Marcucci, Guido, Stein, Anthony S., Forman, Stephen J., Pullarkat, Vinod A., Chen, Wei, Wu, Xiwei, and Nakamura, Ryotaro
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LYMPHOBLASTIC leukemia , *ACUTE leukemia , *GENETIC polymorphisms , *CYTOKINE release syndrome , *SINGLE nucleotide polymorphisms , *CD19 antigen - Abstract
Blinatumomab is a bispecific T cell‐engaging antibody approved for treatment of relapsed/refractory (r/r) ALL, with 40%‐50% complete response (CR)/CR with incomplete count recovery (CRi). Cytokine release syndrome (CRS) as a major adverse effect after blinatumomab therapy. Here, we evaluated the possible association between single‐nucleotide polymorphisms (SNPs) in cytokine genes, disease response, and CRS in r/r ALL patients who received blinatumomab between 2012 and 2017 at our center (n = 66), using patients' archived DNA samples. With a median duration of 9.5 months (range: 1‐37), 37 patients (56.1%) achieved CR/CRi, 54 (81.8%) experienced CRS (G1: n = 35, G2: n = 14, G3: n = 5), and 9 (13.6%) developed neurotoxicity. By multivariable analysis, after adjusting for high disease burden, one SNP on IL2 (rs2069762), odds ratio (OR) = 0.074 (95% CI: NE‐0.43, P =.01) and one SNP on IL17A (rs4711998), OR = 0.28 (95% CI: 0.078‐0.92, P =.034) were independently associated with CR/CRi. None of the analyzed SNPs were associated with CRS. To our knowledge, this is the first study demonstrating a possible association between treatment response to blinatumomab and SNPs. Our hypothesis‐generated data suggest a potential role for IL‐17 and IL‐2 in blinatumomab response and justify a larger confirmatory study, which may lead to personalized blinatumomab immunotherapy for B‐ALL. [ABSTRACT FROM AUTHOR]
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- 2021
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9. Ruxolitinib as adjunctive therapy for secondary hemophagocytic lymphohistiocytosis: A case series.
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Hansen, Sarah, Alduaij, Waleed, Biggs, Catherine M., Belga, Sara, Luecke, Kai, Merkeley, Hayley, and Chen, Luke Y. C.
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PULMONARY aspergillosis , *HEMOPHAGOCYTIC lymphohistiocytosis , *CYTOKINE release syndrome , *OLDER patients , *SYSTEMIC lupus erythematosus , *MACROPHAGE activation syndrome - Abstract
Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a cytokine storm syndrome associated with mortality rates of up to 88%. Standard therapy with high‐dose glucocorticoids and etoposide used in adults is extrapolated from pediatric trials, with significant toxicity in older patients and those with poor performance status. The JAK1/2 inhibitor ruxolitinib has recently gained attention as a treatment option for HLH due to its broad cytokine‐modulating abilities and safety profile. Herein we report our center's experience using ruxolitinib in the treatment of adult‐onset secondary HLH. Case series: We report four patients with profound secondary HLH provoked by diverse triggers, including invasive pulmonary aspergillosis on background systemic lupus erythematosus, disseminated tuberculosis, and T‐cell lymphoma treated with ruxolitinib as monotherapy or combination therapy in upfront and salvage settings. Results: All four patients had rapid, sustained improvement in clinical status, inflammatory markers, and hematological cell counts followed by durable remission. Three patients developed manageable infectious complications postruxolitinib. Conclusions: This series demonstrates the effective use of JAK inhibition with ruxolitinib to control pathological immune activation in critically ill patients with secondary HLH and otherwise limited therapeutic options. JAK inhibition is also an area of urgent investigation for the treatment of cytokine storm associated with COVID‐19. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Blinatumomab in pediatric patients with relapsed/refractory B‐cell precursor acute lymphoblastic leukemia.
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Queudeville, Manon, Schlegel, Patrick, Heinz, Amadeus T., Lenz, Teresa, Döring, Michaela, Holzer, Ursula, Hartmann, Ulrike, Kreyenberg, Hermann, Stackelberg, Arend, Schrappe, Martin, Zugmaier, Gerhard, Feuchtinger, Tobias, Lang, Peter, Handgretinger, Rupert, and Ebinger, Martin
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CHILD patients , *LYMPHOBLASTIC leukemia , *ACUTE leukemia , *HEMATOPOIETIC stem cell transplantation , *CYTOKINE release syndrome - Abstract
Objective: Pediatric patients with relapsed or refractory acute lymphoblastic leukemia have a poor prognosis. We here assess the response rates, adverse events, and long‐term follow‐up of pediatric patients with relapsed/refractory acute lymphoblastic leukemia receiving blinatumomab. Methods: Retrospective analysis of a single‐center experience with blinatumomab in 38 patients over a period of 10 years. Results: The median age at onset of therapy was 10 years (1‐21 years). Seventy‐one percent of patients had undergone at least one hematopoietic stem cell transplantation (HSCT) prior to treatment with blinatumomab. We observed a response to blinatumomab in 13/38 patients (34%). The predominant side effect was febrile reactions, nearly half of the patients developed a cytokine release syndrome. Eight events of neurotoxicity were registered over the 78 cycles (15%). To date, nine patients (24%) are alive and in complete molecular remission. All survivors underwent haploidentical HSCT after treatment with blinatumomab. Conclusions: Despite heavy pretreatment of most of our patients, severe adverse events were rare and response rates encouraging. Blinatumomab is a valuable bridging salvage therapy for relapsed or refractory patients to a second or even third HSCT. [ABSTRACT FROM AUTHOR]
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- 2021
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11. Favorable COVID‐19 course despite significant comorbidities in a ruxolitinib‐treated patient with primary myelofibrosis.
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Koschmieder, Steffen, Jost, Edgar, Cornelissen, Christian, Müller, Tobias, Schulze‐Hagen, Maximilian, Bickenbach, Johannes, Marx, Gernot, Kleines, Michael, Marx, Nikolaus, Brümmendorf, Tim H., and Dreher, Michael
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COVID-19 , *COMORBIDITY , *CYTOKINE release syndrome , *MYELOFIBROSIS , *ADULT respiratory distress syndrome , *CHRONIC kidney failure - Abstract
COVID‐19 carries a high risk of severe disease course, particularly in patients with comorbidities. Therapy of severe COVID‐19 infection has relied on supportive intensive care measures. More specific approaches including drugs that limit the detrimental "cytokine storm", such as Janus‐activated kinase (JAK) inhibitors, are being discussed. Here, we report a compelling case of a 55‐yo patient with proven COVID‐19 pneumonia, who was taking the JAK1/2 inhibitor ruxolitinib in‐label for co‐existing primary myelofibrosis for 15 months prior to coronavirus infection. The patient had significant comorbidities, including chronic kidney disease, arterial hypertension, and obesity, and our previous cohort suggested that he was thus at high risk for acute respiratory distress syndrome (ARDS) and death from COVID‐19. Since abrupt discontinuation of ruxolitinib may cause fatal cytokine storm and ARDS, ruxolitinib treatment was continued and was well tolerated, and the patient´s condition remained stable, without the need for mechanical ventilation or vasopressors. The patient became negative for SARS‐CoV‐2 and was discharged home after 15 days. In conclusion, our report provides clinical evidence that ruxolitinib treatment is feasible and can be beneficial in patients with COVID‐19 pneumonia, preventing cytokine storm and ARDS. [ABSTRACT FROM AUTHOR]
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- 2020
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12. Severe cytokine release syndrome after the first dose of Brentuximab Vedotin in a patient with relapsed systemic anaplastic large cell lymphoma (s ALCL): a case report and review of literature.
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Alig, Stefan K., Dreyling, Martin, Seppi, Bettina, Aulinger, Benedikt, Witkowski, Lukas, and Rieger, Christina T.
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CYTOKINES , *SYNDROMES , *ANTIBODY-drug conjugates , *LYMPHOMAS , *LYMPHATIC diseases , *T-cell lymphoma , *CELL membranes - Abstract
Brentuximab Vedotin is an antibody - drug conjugate targeting CD30. We report a case of severe cytokine release syndrome ( CRS) after administration of the first dose of Brentuximab Vedotin in a 64-yr-old patient with relapsed systemic anaplastic large cell lymphoma (s ALCL). To our knowledge, this is the first case of CRS to Brentuximab Vedotin described in the literature. However, CRS to Brentuximab Vedotin might be underestimated, as the drug has not been tested in large phase III trials yet. [ABSTRACT FROM AUTHOR]
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- 2015
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