The Changing Role of Allogeneic Stem Cell Transplantation in Adult B-ALL in the Era of CAR T Cell Therapy

Abstract

The treatment of B-cell acute lymphoblastic leukemia (B-ALL) in adults remains a significant therapeutic challenge. While advances in chemotherapy and targeted and immunotherapies have improved overall survival, relapsed or refractory (r/r) adult ALL is associated with poor outcomes. CD19-directed chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative option, achieving high remission rates even in heavily pretreated patients. However, relapse is common. Allogeneic hematopoietic stem cell transplantation (allo-HCT), a traditional cornerstone of remission consolidation, may improve long-term outcomes but carries risks of transplant-related mortality (TRM) and morbidity. Most evidence for HCT after CAR T therapy comes from retrospective analyses of subgroups from CAR T cell trials, with small sample sizes and inconsistent data on transplant procedures and outcomes. Despite these limitations, consolidative allo-HCT appears to prolong relapse-free survival (RFS). While overall survival (OS) benefits are in question, extended remission duration has been observed. Nonrelapse mortality (including TRM), ranging from 2.4 to 35%, underscores the need for careful patient selection. Emerging real-world data affirm these findings but highlight the importance of individualized decisions based on disease and treatment history. This review examines current evidence on the sequential use of CD19-directed CAR T-cell therapy and allo-HCT in adults with r/r B-ALL.

Keywords: CD19; acute lymphoblastic leukemia; allogeneic; chimeric antigen receptor T cells; consolidation; hematopoietic transplantation.