CD19/CD22 dual-targeting Chimeric antigen receptor T cell therapy bridging to allogeneic hematopoietic stem cell transplantation for B-cell acute lymphoblastic leukemia delays platelet recovery and increases risks of cytomegalovirus and Epstein-Barr Virus viremia after transplantation

Abstract Integration of chimeric antigen receptor T (CAR-T) cell therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an emerging technology for B-cell acute lymphoblastic leukemia (B-ALL) treatment with unknown impact on HSCT-related complications. We performed a retrospective cohort study of patients receiving CD19/CD22 dual-targeting or CD19 single-targeting CAR-T therapy before HSCT (CD19/CD22 dual-targeting CAR-T group and CD19 single targeting CAR-T group, respectively), and patients did not receive CAR-T therapy before transplantation (non-CAR-T group). Cumulative incidence of platelet engraftment on day 28 was lower in the CD19/CD22 dual-targeting CAR-T group compared to other groups (p=0.028) and it was proved to be an independent risk factor for delayed platelet recovery on day 28 (OR: 2.65; p=0.001). The CD19/CD22 dual-targeting CAR-T bridging to HSCT independently increases risk of early CMV-viremia (HR, 2.96; p=0.001). Both CAR-T groups had higher incidence of 100-day Epstein-Barr virus (EBV)-viremia, compared with the non-CAR-T group (p=0.043 and p=0.001, respectively). Patients receiving CAR-T cell therapy had a higher risk for early EBV-viremia (HR, 6.77; p=0.030). Relapse and survival did not differ between the 3 groups (p>0.05). Integrating CD19/CD22 dual-targeting CAR-T therapy and HSCT delays platelet engraftment and increases the risks of early CMV- and EBV-viremia.