In a large single institutional study reporting on patients with B cell malignancies receiving autologous 2nd generation 4-1BB-containing CD19-directed CAR T cells, risk factors for the development of CRS included the CAR T cell dose, use of fludarabine-containing lymphodepleting conditioning therapy, bone marrow involvement of disease (particularly with B-ALL), and the degree of CAR T cell expansion following cellular infusion [204]. This evidence concerns the gene CD19 and acute lymphoblastic leukemia.