Clinical analysis of donor-derived CD19 chimeric antigen receptor T lymphocytes for the treatment of recu-rrent acute B-cell leukemia after allogeneic hematopoietic stem cell transplantation

Abstract

Objective To discuss the cure effect and side effects of donor anti-CD19 chimeric antigen receptor T lymphocytes(CD19 CAR-T)for treating recurrent acute B-cell leukemia after allogeneic hematopoietic stem-cell transplantation(Allo-HSCT), and to analyze the influencing factors for this therapy. Methods The clinical data of 5 acute B-cell leukemia patients were analyzed retrospectively who relapsed after Allo-HSCT and received donor CD19 CAR-T therapy at Beijing Children′s Hospital from July 2015 to October 2017.Disease status before infusion, conditioning regimen, reinfusion cell dose, and side-effect of CAR-T infusion, changes in the related immunological indicators, and follow-up treatment results were investigated. Results One patient had no effect, other patients got remission or minimal residual disease(MRD) negative within 4 weeks after CAR-T infusion, and the middle time was 14 days.Peripheral CAR-T peak happened 2 weeks after CAR-T infusion.By the last follow, 2 patients died of leukemia, 3 patients were alive, and 1 case of them lived with tumor after CD19 negative relapse, others lived with disease-free condition.Cytokine release syndrome(CRS) was the most common side effect, happening in 1 to 2 weeks after infusion, 1 patient had neurologic toxicities, and 2 patients had suspicious graft-versus-host disease. Conclusions Donor CD19 CAR-T therapy has a good short-term effect for relapsed B-cell leukemia patients after Allo-HSCT, but long-term effect requires further observation; CRS is the most common side-effect.Off-target and cell exhaustion are the main reasons for defeat. Key words: Donor chimeric antigen receptor T cell; CD19; Relapse acute leukemia; Allogeneic hematopoietic stem cell transplantation