Patient-derived xenograft model for NI and CRS. (A) Experimental schema: mice received 1 to 3 × 10⁶ blasts derived from the peripheral blood of patients with ALL. Mice were monitored for engraftment for ∼10 to 13 weeks via tail vein bleeding. When serum CD19⁺ cells were ≥10 per microliter, the mice received CART19 cells (2 to 5 × 10⁶ cells) and commenced antibody therapy for a total of 10 days, as indicated. Mice were weighed on a daily basis as a measure of their well-being. Mouse brain MRIs were performed 5 or 6 days post–CART19 cell injection, and tail vein bleeding for cytokine/chemokine and T cell analysis was performed 4 to 11 days post–CART19 cell injection; 2 independent experiments. (B) Combination of GM-CSF neutralization with CART19 cells is equally effective as isotype control antibodies combined with CART19 cells in controlling CD19⁺ burden of ALL cells; representative experiment, 3 mice per group, 11 days post–CART19 cell injection. Data are mean ± SEM. (C) Brain MRI with CART19 cell therapy exhibits T1 enhancement, suggestive of blood–brain barrier disruption and possible edema; 3 mice per group, 5 or 6 days post–CART19 cell injection, representative image. (D) High tumor burden ALL patient–derived xenografts (PDX) treated with CART19 cells show human CD3 cell infiltration of the brain compared with untreated PDX controls; 3 mice per group, representative image. *P < .05, Student t test.