Cytokine Release Syndrome in the Immunotherapy of Hematological Malignancies: The Biology behind and Possible Clinical Consequences

Abstract

Cytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction associated with (i) chimeric antigen receptor (CAR)-T cell therapy, (ii) therapeutic antibodies, and (iii) haploidentical allogeneic stem cell transplantation (haplo-allo-HSCT). Severe CRS can be life-threatening in some cases and requires prompt management of those toxicities and is still a great challenge for physicians. The pathophysiology of CRS is still not fully understood, which also applies to the identifications of predictive biomarkers that can forecast these features in advance. However, a broad range of cytokines are involved in the dynamics of CRS. Treatment approaches include both broad spectrum of immunosuppressant, such as corticosteroids, as well as more specific inhibition of cytokine release. In the present manuscript we will try to review an update regarding pathophysiology, etiology, diagnostics, and therapeutic options for this serious complication.

Pretransplant Systemic Lipidomic Profiles in Allogeneic Stem Cell Transplant Recipients

“…We know that inflammation [ 13 ] and fluid overload [ 12 ] seem to have a prognostic impact for various allotransplanted patient subsets, and GVHD is also a general problem in allotransplant recipients [ 77 ]. Despite this, the immunobiology of various allotransplant recipients differ, e.g., GVHD is less important in umbilical cord transplantation [ 78 ] and the cytokine release syndrome is seen especially in haploidentical transplantation [ 79 ]. Finally, our analyses of posttransplant complications and survival should be interpreted with great care because differences between metabolic/lipidomic patient subsets can (at least partly) be caused by differences in conditioning therapy; this is true especially for the patient subsets identified in Figure 1 .…”

Recovery-Model: a model for CAR T-cell-related thrombocytopenia in relapsed/refractory Multiple myeloma

“…After CAR-T infusion, the tumor cells and CAR-T cells released cytokines such as TNF-α and IFN-γ. Then immunocompetent cells and stromal cells (e.g., endothelial cells) were activated and released proin ammatory cytokines, resulting the positive feedback loop of CRS [15]. There was a hypothesis that the high levels of circulating cytokines such as IFN, tumor TNF, and IL-6 could lead to hematotoxicity through in ammatory damage to the bone marrow [16].…”

“…Moreover, a variety of in ammatory factors such as IL-6 and IFN-γ had also been shown to be associated with the proliferation and development of hematopoietic stem cells [17][18][19]. Increased levels of ferritin indicated macrophage activation or hemophagocytic lymphohistiocytosis (HLH) which was a hyperin ammatory syndrome that shared common features with CRS [15]. Thus, those myelosuppressive in ammation-related factors might contribute to thrombocytopenia.…”

Biological effects of COVID-19 on lung cancer: Can we drive our decisions

“…One of the most important aspects related to COVID-19 is the cytokine storm, during which various inflammatory cytokines are developed, and the consequent cytokine release syndrome (CRS), which represents an acute attack of excessive cytokines from the immune system triggered by inflammatory responses and the immunity ( 96 , 97 ). The CRS is characterized by high fever, erythema, edema, extreme fatigue, and nausea, which may also be associated with sepsis and multiple organ failure ( 98 ). The first approach by the cytokines and chemokines represents an important step against the viral infection; in particular, macrophages function as sentinels in the lungs, and SARS-CoV2 can infect these to induce this cascade as an early pathogenic mechanism ( 99 , 100 ).…”