[Management of cytokine release syndrome in adult and pediatric patients undergoing CAR-T cell therapy for hematological malignancies: Recommendation of the French Society of Bone Marrow and cellular Therapy (SFGM-TC)].

The cytokine release syndrome (CRS) is the most common complication after adoptive immunotherapies such as chimeric antigen receptor T cells (CAR-T). The incidence varies from 30 to 100% depending on the CAR-T construct, cell doses and the underlying disease. Severe cases may involve 10 to 30% of patients. The triggering event is the activation of the CAR-T, after meeting with their target. The T cell activation leads to the release of effector cytokines, such as IFNγ, TNFα and IL2, that are responsible for the activating of monocyte/macrophage system, resulting in the production of pro-inflammatory cytokines, (including IL6, IFN-γ, IL10, MCP1) and associated with a significant elevation of CRP and ferritin. The CRS usually appears between 1 and 14days after the infusion of the cells and can last from 1 to 10days. Rare fatal cases have been reported in the literature. The first symptom is often a fever, sometimes very high, which must alert and reinforce the surveillance. In moderate forms, one can find fatigue, headache, rash, arthralgia and myalgia. T cell-related encephalopathy (CRES) syndrome may occur concomitantly. In case of aggravation, a vasoplegic shock associating capillary leakage and respiratory distress can occur. Close clinical monitoring is essential right from the injection to quickly detect the first symptoms. The treatment of severe forms, in addition to symptomatic management involves monoclonal antibodies targeting the IL6 or IL6 receptor, and sometimes steroids. Close cooperation with intensive care units is essential since 20 to 50% of patients require intensive care unit transfer.

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