供者CD19 CAR-T细胞治疗急性B淋巴细胞白血病移植后复发九例临床观察

OBJECTIVE: To investigate the long term efficacy and side effects of a donor-derived CD19 chimeric antigen receptor（CAR）T-cell（HI19α-4-1BB-ζ CAR-T）therapy in the treatment of patients with relapsed B-cell acute lymphoblastic leukemia（B-ALL）after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. METHODS: A total of 9 subjects with relapsed B-ALL post allo-HSCT received donor-derived CD19 CAR-T therapy from July 2017 to May 2020. All subjects were infused with donor CD3-positive T cells after lymphodepletion chemotherapy, and a median dose of CAR-T cells was 1.79（range, 0.86–3.53）×10(6)/kg. RESULTS: ①All subjects achieved complete remission and MRD-negative at 28–42 d post CAR-T cells infusion. ②Cytokine releasing syndrome（CRS）occurrd in all subjects and was grade 3 in 2, grade 2 in 4, grade 1 in 3 cases respectively. Four subjects developed immune effector cell-associated neurotoxicity syndrome（ICANS）, which was grade 2 in 1, grade 1 in 3. One subject developed grade IV acute graft-versus-host disease（GVHD）, and side effects were all controllable. ③Four subjects relapsed at a median period of 8.6（4.6–19.3）months, 2 subjects died of disease progression after receiving chemotherapy and another one also died of disease progression 14 months after a second transplant, only 1 subject achieved complete remission after CD22 CAR-T cell therapy. Until last follow-up date, 6 subjects were leukemia-free and achieved complete donor chimerism. The estimated 1-year and 2-year leukemiafree survival（LFS）rate was 63.5％ and 50.8％, with a median LFS of 18.1 months. ④After a median follow-up of 25.1（range, 6.9–36.7）months, the estimated 2-year and 2.5-year OS rate were 87.5％ and 52.5％, respectively. CONCLUSION: The donor-derived CD19 CAR-T cell therapy obtain a high remission rate in relapsed B-ALL patients post allo-HSCT with tolerable side effects, half subjects survived more than 2 years without disease recurrence, though long-term efficacy requires further observation.