Unity brings strength: Combination of CAR-T cell therapy and HSCT

Abstract

With the rapid revolution of therapies, hemopoietic stem cell transplantation (HSCT) has become a widely promoted treatment for hematological malignancies. High-dose chemotherapy (HDCT) followed by autologous blood cell (ABC) transplantation is a standard procedure for patients with primary relapse B-cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), and allogeneic HSCT is one of the few treatments for patients with acute leukemia. However, refractory and recurrent disease has a negative impact on disease-free survival (DFS) for patients after HSCT. Furthermore, complications such as GVHD and infection significantly impair the quality of life and life expectancy of patients who receive allogeneic HSCT. The promising efficacy of chimeric antigen receptor T (CAR-T) cell therapy for relapsed or refractory B-cell acute lymphoblast leukemia (ALL) has offered hope for patients with R/R hematological malignancies. However, the long-term survival of patients after CAR-T cell therapy is also threatened by recurrent disease, and relapse occurs in half of patients who achieve remission. In addition, the rapid proliferation of CAR-T cells will cause damage to the balance of the immune system, leading to cytokine release syndrome (CRS) and CAR-T cell-related encephalopathy syndrome (CRES). Although therapeutic regimens such as IL-6 pathway blockers have obvious impacts on the side effects related to CAR-T cell therapy, there are still reports of patient deaths in past clinical trials. Based on the characteristics of HSCT and CAR-T cell therapy, it is unclear whether there is a better combination of cutting-edge immune cell therapy and traditional transplantation to improve the prognosis of patients. This review focuses on the possible ways to take full advantage of each therapy in the treatment of hematological malignancies.