The possible reasons were that: (1) the activation of CAR-T cells was driven by recognition and binding to CD19 on malignant B cells; therefore, heavier disease burden might lead to higher level of CD19-expressing B cells, which possibly promoted activation of CAR-T cells as well as increased secretion of cytokines, thereby raising the risk of severe CRS in R/R B-ALL patients. The gene discussed is CD19; the disease is acute lymphoblastic leukemia.