To overcome the treatment failure caused by immunogenicity of scFv from murine CD19 CAR in patients with prior mCD19 CAR-T exposure, we applied humanized CD19 CAR-T cells to treat r/r B-ALL patients who relapsed after or had no response to mCD19 CAR-T but still showed high levels of CD19 expression. This evidence concerns the gene CD19 and acute lymphoblastic leukemia.