Background: Anti-CD19 Chimeric Antigen Receptor T-Cell Immunotherapy (19CAR-T) has achieved impressive clinical achievements in both adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedullary relapse are rarely issued even disqualified in some clinical trials. Here, we examined the efficacy of 19CAR-T in patients with both bone marrow and extramedullary involvement.

Methods: CAR-T cells were generated by a lentiviral vector transfection into primary human T lymphocytes to express anti-CD19 and anti-CD22 single chain antibody fragments (scFvs) with the cytoplasmic domains of 4-1BB and CD3ζ. Patients diagnosed as r/r B-ALL with extramedullary origination were infused with anti-CD19 CAR-T cells. The clinical responses were evaluated by bone marrow aspiration, imaging, and flow cytometry examination.

Results: A total of 8 patients received 19CAR-T infusion and all of them acquired complete remission (CR), in which only 1 patient was bridged to hematopoietic stem cell transplantation (HSCT). Even though there were 3 patients relapsed after infusion, they received 19/22CAR-T infusion sequentially and acquired the second remission. To date, 5 patients are continuous CR, and all patients are still alive. The mean follow-up time was 21.9 months while the 24-month estimated event-free survival (EFS) is 51.4%.

Conclusions: Anti-CD19 CAR-T therapy can lead to clinical remission for extramedullary relapsed pediatric B-ALL patients. However, the problem of CD19+ relapses after CAR-T remained to be solved. For patients relapsing after CAR-T, the second CAR-T therapy suggests creating another opportunity of remission for subsequent HSCT.