Chimeric antigens receptor T cell therapy as a bridge to haematopoietic stem cell transplantation for refractory/...

Although chimeric antigen receptor T cells (CAR-T) targeted at CD19 or CD22 have achieved high complete remission (CR) in refractory/relapsed B-cell acute lymphoblastic leukaemia (B-ALL), it is uncertain if allogeneic haematopoietic stem cell transplantation (allo-HSCT) should be performed after CAR-T therapy to accomplish a sustainable remission. Fifty-two cases with relapsed/refractory B-ALL who underwent allo-HSCT after CR by CD19 or CD22 CAR-T were enrolled. The median time from CAR-T infusion to allo-HSCT was 50 (34-98) days. Myeloablative reduced-intensity conditioning (RIC) with total body irradiation/fludarabine-based or busulfan/fludarabine-based regimens was used. Incidences of grade II-IV acute graft-versus-host disease (aGVHD) and severe aGVHD were 23·1% and 5·8% respectively. Of 48 evaluable cases, 16 developed chronic GVHD (cGVHD) and in three of them the pattern was extensive. With a median follow-up of 334 (41-479) days, one-year overall survival and event-free survival (EFS) were 87·7% and 73·0%. One-year relapse rate and transplant-related mortality (TRM) were 24·7% and 2·2% respectively. With quick bridge to allo-HSCT after CAR-T therapy, high EFS for refractory/relapsed B-ALL has been achieved in this relatively large cohort. Our myeloablative RIC regimens have resulted in low incidences of aGVHD, cGVHD, viral reactivation and very low TRM even majority of transplants from haploidentical donors. Long-term follow-up is warranted.