BACKGROUND: Reduced-intensity conditioning (RIC) regimens with low tolerable toxicities have been used for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the relapse rate by this treatment is high. Treatment of CD19 B-cell relapsed/refractory acute lymphoblastic leukemia (r/r ALL) with allogeneic chimeric antigen receptor-modified T (CAR-T) cells is safe and effective. Use of allogeneic CD19-CAR-T cells as a part of RIC regimens for treatment of r/r ALL patients with haploidentical HSCT has not been investigated yet. CASE PRESENTATION: A 12-year-old girl with CD19 r/r ALL underwent haploidentical HSCT. The patient received fludarabine, busulfan, and cyclophosphamide combined with haploidentical donor-derived CD19-CAR-T cells as the conditioning regimen. Granulocyte colony-stimulating factor-mobilized peripheral blood stem cells and granulocyte colony-stimulating factor-mobilized bone marrow were infused on days 1 and 2, respectively. Mycophenolate mofetil and tacrolimus were administered on day 1, antithymocyte globulin was administered on days +14 and +15, and a short course of methotrexate was administered to prevent graft-versus-host disease. The time of peak CAR-T cell proliferation was detected after the first infusion of CAR-T cells on day 7. The patient's engraftment and full-donor cell engraftment were established. The disease was in complete remission with minimal residual disease, which was undetectable by flow cytometry. No graft-versus-host disease or serious cytokine-release syndrome was found. CONCLUSIONS: Treatment of r/r ALL with RIC including CD19-CAR-T cells followed by allo-HSCT was safe and effective, which suggest that CAR-T cells can be used as a part of RIC regimens in the treatment of r/r ALL in haploidentical HSCT.
BACKGROUND: Reduced-intensity conditioning (RIC) regimens with low tolerable toxicities have been used for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the relapse rate by this treatment is high. Treatment of CD19 B-cell relapsed/refractory acute lymphoblastic leukemia (r/r ALL) with allogeneic chimeric antigen receptor-modified T (CAR-T) cells is safe and effective. Use of allogeneic CD19-CAR-T cells as a part of RIC regimens for treatment of r/r ALL patients with haploidentical HSCT has not been investigated yet. CASE PRESENTATION: A 12-year-old girl with CD19 r/r ALL underwent haploidentical HSCT. The patient received fludarabine, busulfan, and cyclophosphamide combined with haploidentical donor-derived CD19-CAR-T cells as the conditioning regimen. Granulocyte colony-stimulating factor-mobilized peripheral blood stem cells and granulocyte colony-stimulating factor-mobilized bone marrow were infused on days 1 and 2, respectively. Mycophenolate mofetil and tacrolimus were administered on day 1, antithymocyte globulin was administered on days +14 and +15, and a short course of methotrexate was administered to prevent graft-versus-host disease. The time of peak CAR-T cell proliferation was detected after the first infusion of CAR-T cells on day 7. The patient's engraftment and full-donor cell engraftment were established. The disease was in complete remission with minimal residual disease, which was undetectable by flow cytometry. No graft-versus-host disease or serious cytokine-release syndrome was found. CONCLUSIONS: Treatment of r/r ALL with RIC including CD19-CAR-T cells followed by allo-HSCT was safe and effective, which suggest that CAR-T cells can be used as a part of RIC regimens in the treatment of r/r ALL in haploidentical HSCT.
Authors: Sun Yao; Chen Jianlin; Liu Yarong; Li Botao; Wang Qinghan; Fang Hongliang; Zhang Lu; Ning Hongmei; Wang Pin; Chen Hu; Hu Liangding; Zhang Bin Journal: Front Oncol Date: 2019-12-03 Impact factor: 6.244