Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has made tremendous progress in the last few decades and is increasingly being used worldwide. The success of haploidentical HSCT has made it possible to have “a donor for everyone”. Patients who received transplantation in remission may have a favorable outcome, while those who were transplanted in advanced stages of disease have a poor prognosis. Although chimeric antigen receptor T (CAR-T) cell therapy is currently a milestone in the immunotherapy of relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL) and has demonstrated high remission rates in patients previously treated in multiple lines, the relatively high relapse rate remains a barrier to CAR-T cell therapy becoming an excellent cure option. Therefore, combining these two approaches (allo-HSCT and CAR-T cell therapy) is an attractive area of research to further improve the prognosis of R/R B-ALL. In this review, we will discuss the current clinical practices of combining allo-HSCT with CAR-T cell therapy based on available data, including CAR-T cells as a bridge to allo-HSCT for R/R B-ALL and CAR-T cell infusion for post-transplant relapse. We will further explore not only other possible ways to combine the two approaches, including CAR-T cell therapy to clear minimal residual disease peri-transplantation and incorporation of CAR technology to treat graft-versus-host disease, but also the potential of CAR-T cells as a part of allo-HSCT.
Highlights
Allogeneic hematopoietic stem cell transplantation has achieved great progress in the past few decades
Advances in graft-versus-host disease (GVHD) prophylaxis and supportive care have significantly improved the outcomes of allo-HSCT
There was no significant difference in event-free survival (EFS) and overall survival (OS) between minimal residual disease (MRD)-negative patients who underwent allo-HSCT and those who did not
Summary
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has achieved great progress in the past few decades. The relapse rate of B-ALL after CAR-T cell therapy was 20–70% when the follow-up period was long enough [22]. For pediatric and young adult patients with R/R B-ALL, a phase 1/2a study involved 30 patients treated with CD19 CAR-T cell therapy. The EFS and OS rates at 12 months were 50 and 76%, and the median duration of remission was still not reached after a median follow-up of 13.1 months In both studies, the persistence of CAR-T cells and the duration of B cell aplasia were long. Leukemia-free survival (LFS, 76.9 vs 11.6%, P
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