While gene mutation, pre-treatment with blinatumomab, and RNA splice variants [60,61,62] can explain most of the cases of CD19-negative relapse, down-regulation of the target antigen can take place with other CAR T-cell therapies of B-ALL as anti-CD22 CAR T-cell therapy [63]. This evidence concerns the gene CD19 and precursor B-cell acute lymphoblastic leukemia.