Risk factors for severe CRS include patient-related factors (B-ALL diagnosis, high tumor burden, baseline thrombocytopenia, and endothelial activation), tumor-related factors (B-ALL diagnosis), and treatment-related factors (high number of infused CAR-T cells, high peak of CAR-T cell expansion, CD28 co-stimulatory, high-intensity lymphodepletion regimens) (Jin et al., 2018; Ganatra et al., 2019b; Zheng et al., 2020; Schubert et al., 2021). The gene discussed is CD28; the disease is acute lymphoblastic leukemia.