How to Combine the Two Landmark Treatment Methods—Allogeneic Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Together to Cure High-Risk B Cell Acute Lymphoblastic Leukemia?

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.

HSCT with mismatched unrelated donors: Bone marrow versus peripheral blood stem cells sources in pediatric patients

“…At present, there are an increasing number of clinical studies in this field. As more studies confirm the results, the clearance of MRD will greatly expand the application of CAR‐T cell therapy 36–38 . Regarding CIK cells, a recent Stanford University publication on 44 patients showed that early administration (day +21–35) of a single dose of allogeneic CIK cells (1 × 10 8 ) did not cause significant immunological complications 39,40 …”

“…As more studies confirm the results, the clearance of MRD will greatly expand the application of CAR-T cell therapy. [36][37][38] Regarding CIK cells, a recent Stanford University publication on 44 patients showed that early administration (day +21-35) of a single dose of allogeneic CIK cells (1 × 10 8 ) did not cause significant immunological complications. 39,40 In conclusion, we were able to demonstrate how the combination of ATG-Cyclosporin-A and MTX together with the bone marrow as HSC source was associated with a high probability of survival after MMUD HSCT.…”

Bibliometric Analysis of Chimeric Antigen Receptor-Based Immunotherapy in Cancers From 2001 to 2021

“…Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is another hotly debated topic. The combination of allo-HSCT and CAR-T therapy seem to provide benefit for patients with advanced diseases, particularly high-risk B-cell acute lymphoblastic leukemia (B-ALL) ( 42 ). However, the ideal application sequence of the two landmark therapies, the optimal therapeutic window for post allo-HSCT CAR-T infusion, the value of CAR-T in treating peri-transplantation minimal residual disease (MRD), and the utility of CAR-base technology in treating graft-versus-host disease (GVHD), the most frequent complication after allo-HSCT, remain unclear ( 43 ).…”

CAR-T after Stem Cell Transplantation in B-Cell Lymphoproliferative Disorders: Are They Really Autologous or Allogenic Cell Therapies?

“…Even though the most common application is CAR-T after the failure of an allo-HSCT, some studies are already testing CAR-T before transplantation as a bridge towards allo-HSCT. This strategy might allow an effective way to induce remission, reducing tumor burden, and therefore improving the outcome of the subsequent allo-HSCT [ 49 , 69 , 70 ]; however, CAR-T therapy is only at the beginning of its application, and many problems and difficulties are still avoiding its widespread application; standardization of the T-cell source to manufacture CAR-T is an active area of research that in the next few years will undoubtedly benefit the efficacy of CAR-T therapy.…”