Multiple CAR-T cell therapy for acute B-cell lymphoblastic leukemia after hematopoietic stem cell transplantation: A case report

Abstract

B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. The cure rate has reached 90% after conventional chemotherapy and hematopoietic stem cell transplantation (HSCT), but the prognosis of patients with relapsed and refractory (R/R) leukemia is still poor after conventional treatment. Since FDA approved CD19 CAR-T cell (Kymriah) for the treatment of R/R B-ALL, increasing studies have been conducted on CAR-T cells for R/R ALL. Herein, we report the treatment of a patient with ALL who relapsed after allogeneic HSCT, had a complete remission (CR) to murine scFv CD19 CAR-T but relapsed 15 months later. Partial response was achieved after humanized CD19 CAR-T treatment, and the patient finally achieved disease-free survival after sequential CD22 CAR-T treatment. By comparing the treatment results of different CAR-T cells in the same patient, this case suggests that multiple CAR-T therapies are effective and safe in intramedullary and extramedullary recurrence in the same patient, and the expansion of CAR-T cells and the release of inflammatory cytokines are positively correlated with their efficacy. However, further clinical studies with large sample sizes are still needed for further clarification.

Conditional CAR T cells with specificity to oncofetal glycosaminoglycans in solid tumors

“…CARs are genetically engineered synthetic antigen receptors that are able to activate upon antigen recognition, independent of MHC presentation (24,25). CAR T cell therapy has achieved unprecedented success in treating patients with hematopoietic malignancies, such as acute B-cell lymphoblastic leukaemia and B-cell lymphomas (23,(26)(27)(28). However, only a few studies have shown promise for CAR T cell therapy in solid tumors, such as GD2-CAR T cells for relapsed and refractory Neuroblastoma tumors (29), as well as B7H3-, GD2-and IL13RA2-CAR T cells for human Glioma (30)(31)(32).…”