Rapid identification of cytokine release syndrome after haploidentical PBSC transplantation and successful therapy with tocilizumab

Cho, C; Perales, Miguel-Ángel

doi:10.1038/bmt.2016.229

Cited by 18 publications

(9 citation statements)

References 10 publications

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“…Cumulative incidence (CI) of neutrophil engraftment at day +30 was 96% (95% CI, 92-100) achieved in a median of 17 days (range [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] and CI of platelet engraftment at day +100 was 94% (95% CI, 90-98) in a median of 29 days (range 15-226). CI of achievement of complete donor chimerism at day +100 was 93% (95% CI, 89.8-100).…”

Section: Resultsmentioning

confidence: 99%

“…Only one patient reached grade 3 CRS and required treatment with tocilizumab. Emerging clinical experience has shown that tocilizumab is an effective treatment for severe CRS, not only after CAR-T cell therapy but also after haplo-HSCT, 3,[17][18][19] , based on the blockade of IL-6 receptor. Although experience is scarce compared to the emerging CAR-T cell therapy induced CRS, criteria for IL-6 blockade might be similar in the HSCT setting.…”

Section: Discussionmentioning

confidence: 99%

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Cytokine release syndrome after allogeneic stem cell transplantation with posttransplant cyclophosphamide

Solán

Landete

Bailén

et al. 2020

Hematological Oncology

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Cytokine release syndrome (CRS) is a systemic inflammatory response with aberrant immune activation and immune hyperstimulation, that leads to increased cytokine levels and inflammation. CRS has been described after antibody and cellular-based therapies. The use of posttransplant cyclophosphamide (PTCy) as graft-vs-host disease (GVHD) prophylaxis in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has led to the extension of allogeneic HSCT to patients without HLA-identical donors. Furthermore, PTCy has also been introduced in matched and unrelated donor HSCT. However, description of incidence and clinical impact of CRS on outcomes in these patients is scarce. We retrospectively analyzed 107 consecutive haplo-HSCT and 39 HLA-identical HSCT with PTCy from 2010 to 2017 in our institution. We used published CRS criteria to identify 76% and 14% of patients who developed CRS after haplo-HSCT and HLA-identical HSCT, respectively. Most patients presented CRS grades 1 and 2. Only one patient from the whole series presented grade 3 CRS and required tocilizumab therapy. The use of peripheral blood stem cells (PBSC), as well as total nucleated cells infused were associated with an increased risk of CRS. Patients who presented CRS developed grade II-IV acute GVHD more frequently than those who did not (60% vs 28.6% respectively, P = .012). The development of CRS was not significantly associated with nonrelapse mortality or overall survival. CRS is a frequent complication after PBSC haploidentical T-repleted HSCT, but significantly less frequent after HLA-identical HSCT. Most cases are mild. Prompt identification allows adequate management of severe forms. K E Y W O R D S cyclophosphamide, cytokine release syndrome, haploidentical stem cell transplantation, hematopoietic stem cell transplantation 1 | INTRODUCTION Cytokine release syndrome (CRS) is a systemic inflammatory response that occurs as a result of high-level immune activation. With the extended use of inmune-based therapies CRS has been increasingly recognized. 1 However, the pathophysiology of CRS is still incompletely understood. CRS is triggered by the massive release of IFN-γ by activated Tcells and / or tumor cells after the administration of antibody-based therapies, nonprotein-based cancer drugs such as oxaliplatin and lenalidomide and, recently, the new T-cell engaging immunotherapies including bispecific antibody constructs and chimeric antigen receptor (CAR) T cells. IFN-γ causes activation of different immune cells especially macrophages. Activated macrophages produce a cascade Jose Luis Díez-Martín and Mi Kwon contributed equally to this study.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cytokine release syndrome after allogeneic stem cell transplantation with posttransplant cyclophosphamide

Solán

Landete

Bailén

et al. 2020

Hematological Oncology

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“…similar infusion reactions including antibody-based therapies (157)(158)(159)(160)(161)(162)(163)(164) and cancer therapeutics (165,166). Other reported stimuli for the development of CRS include haploidentical donor stem cell transplantation, graft-vs.-host disease (167,168), and respiratory viral infections including influenza (11,169). Most recently, new classes of immunotherapeutic agents are used in a variety of hematologic malignancies including bispecific antibody constructs and chimeric antigen receptor (CAR) T cell therapies.…”

Section: The Nlrp3 Inflammasome In Cytokine Release Syndromesmentioning

confidence: 99%

Targeting the NLRP3 Inflammasome in Severe COVID-19

2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the genus Betacoronavirus within the family Coronaviridae. It is an enveloped single-stranded positive-sense RNA virus. Since December of 2019, a global expansion of the infection has occurred with widespread dissemination of coronavirus disease 2019 (COVID-19). COVID-19 often manifests as only mild cold-like symptomatology, but severe disease with complications occurs in 15% of cases. Respiratory failure occurs in severe disease that can be accompanied by a systemic inflammatory reaction characterized by inflammatory cytokine release. In severe cases, fatality is caused by the rapid development of severe lung injury characteristic of acute respiratory distress syndrome (ARDS). Although ARDS is a complication of SARS-CoV-2 infection, it is not viral replication or infection that causes tissue injury; rather, it is the result of dysregulated hyperinflammation in response to viral infection. This pathology is characterized by intense, rapid stimulation of the innate immune response that triggers activation of the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway and release of its products including the proinflammatory cytokines IL-6 and IL-1β. Here we review the literature that describes the pathogenesis of severe COVID-19 and NLRP3 activation and describe an important role in targeting this pathway for the treatment of severe COVID-19.

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“…CRS has also been observed following administration of non-protein-based cancer drugs such as oxaliplatin [ 11 ] and lenalidomide [ 12 ]. Furthermore, CRS was reported in the setting of haploidentical donor stem cell transplantation, and graft-versus-host disease [ 13 , 14 ]. Cytokine storm due to massive T cell stimulation is also a proposed pathomechanism of severe viral infections such as influenza [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Cytokine release syndrome

Shimabukuro‐Vornhagen

Gödel

Subklewe

et al. 2018

j. immunotherapy cancer

1,258

1,163

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During the last decade the field of cancer immunotherapy has witnessed impressive progress. Highly effective immunotherapies such as immune checkpoint inhibition, and T-cell engaging therapies like bispecific T-cell engaging (BiTE) single-chain antibody constructs and chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in clinical trials and some of these agents have already received regulatory approval. However, along with growing experience in the clinical application of these potent immunotherapeutic agents comes the increasing awareness of their inherent and potentially fatal adverse effects, most notably the cytokine release syndrome (CRS). This review provides a comprehensive overview of the mechanisms underlying CRS pathophysiology, risk factors, clinical presentation, differential diagnoses, and prognostic factors. In addition, based on the current evidence we give practical guidance to the management of the cytokine release syndrome.

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Rapid identification of cytokine release syndrome after haploidentical PBSC transplantation and successful therapy with tocilizumab

Cited by 18 publications

References 10 publications

Cytokine release syndrome after allogeneic stem cell transplantation with posttransplant cyclophosphamide

Cytokine release syndrome after allogeneic stem cell transplantation with posttransplant cyclophosphamide

Targeting the NLRP3 Inflammasome in Severe COVID-19

Cytokine release syndrome

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