Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Relapse/Refractory B-ALL Patients After Chimeric Antigen Receptor T Cell Therapy: A Systematic Review and Meta-analysis

Abstract

Background: Allogeneic hematopoietic stem cell transplantation(allo-HSCT) consolidation therapy after chimeric antigen receptor(CAR) T cell therapy has emerged as an alternative in patients with B-ALL in the past decade. However, the efficiency remains unclear. In this study, we aimed to systematically analysis the effect of allo-HSCT for Relapse/Refractory(R/R) B-ALL patients after CAR-T cell therapy on survival and relapse rate(RR). Methods: We searched potential documents up to Jan.31st, 2021 in PUBMED, EMBASE, Cochrane Library and Springer and analyzed them by Cochrane Collaboration RevMan 5.3 software. Results: Allo-HSCT was efficient in improving short(6-month) and long(1-year and 2-year) term overall survival(OS) and leukemia-free survival(LFS). Transplantation could also reduce RR of R/R B-ALL regardless of patients’ characteristics and time of allo-HSCT. Besides, CAR-T cell products with 4-1BB domain bridging allo-HSCT were associated with a better survival. Subgroup analysis indicated allo-HSCT was more likely to exert a noticeable influence on survival of junior individuals(≤40) and Asian groups. A suitable period between allo-HSCT and CAR-T cell therapy(≤70 days) would make a difference. Interestingly, some features of patients, such as a HSCT history or BCR-ABL1 rearrangement (Philadelphia chromosome, Ph) may have an effect on the efficacy of allo-HSCT. Conclusion: Allo-HSCT consolidation therapy after CAR-T cell therapy induced a promising short-and-long term survival of R/R B-ALL patients. Senior patients, prior HSCT history and BCR-ABL1 rearrangement (Ph) might be poor prognostic factors. Further studies are needed to explore the optimal time for allo-HSCT.