Consolidative Hematopoietic Stem Cell Transplantation After CD19 CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: A Systematic Review and Meta-analysis

Background: This study aims to systematically evaluate and compare the efficacy and safety of consolidative hematopoietic stem-cell transplantation (HSCT) after CD19 chimeric antigen receptor T (CAR-T) therapy with non-HSCT in the treatment of acute lymphoblastic leukemia (ALL). Methods: The PubMed, Embase, Cochrane Library and Web of Science databases were searched for clinical trials. Pooled hazard ratios (HRs) for overall survival (OS), relapse rate, and leukemia-free survival (LFS) as well as the overall incidence rates for transplant-related mortality (TRM), acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD) and infections were calculated using Stata software. Results: We screened 3441 studies and identified 24 eligible studies with 770 patients. Our results revealed that among patients who achieved CR after CD19 CAR-T therapy, consolidative HSCT was beneficial with respect to OS (HR=0.34, 95% CI, 0.17-0.68, P=0.003), relapse rate (HR=0.16, 95% CI, 0.10-0.25, P<0.001) and LFS (HR=0.15, 95% CI, 0.08-0.28, P<0.001). For patients who achieved MRD-negative (neg) CR after CD19 CAR-T therapy, consolidative HSCT was beneficial with respect to OS (0.42, 95% CI, 0.28-0.64, P<0.001), relapse rate (0.15, 95% CI, 0.09-0.26, P<0.001), and LFS (0.22, 95% CI, 0.15-0.33, P<0.001). Regarding safety, we calculated the pooled incidence rates for TRM (10%, 95% CI, 0.04-0.17), aGVHD (49%, 95% CI, 0.30-0.69), cGVHD (38%, 95% CI, 0.22-0.54), and infections (41%, 95% CI, 0.07-0.81). Conclusions: Compared to non-HSCT treatment, the use consolidative HSCT after CD19 CAR-T therapy for R/R B-ALL patients can prolong OS and LFS and reduce the risk of relapse. The incidence rates for adverse events are acceptable.