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

Background This study aimed 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 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 3,441 studies and identified 19 eligible studies with 690 patients. Among the patients who achieved complete remission (CR) after CD19 CAR-T therapy, consolidative HSCT was beneficial for OS (HR = 0.34, 95% CI, 0.17-0.68, P = 0.003), the 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 for OS (0.57, 95% CI, 0.33-0.99, P = 0.045), the relapse rate (0.14, 95% CI, 0.06-0.31, P < 0.001), and LFS (0.21, 95% CI, 0.12-0.35, P < 0.001). Regarding safety, we calculated pooled incidence rates for TRM (8%, 95% CI, 0.02-0.15), aGVHD (44%, 95% CI, 0.23-0.67), cGVHD (36%, 95% CI, 0.17-0.56), and infections (39%, 95% CI, 0.03-0.83). Conclusions Compared with non-HSCT treatment, 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. More high-quality randomized controlled trials are required to avoid bias and further determine the efficacy of HSCT.

Automated summary

This study systematically evaluated and compared the efficacy and safety of consolidative HSCT after CD19 CAR-T therapy with non-HSCT in the treatment of ALL. The results showed that consolidative HSCT after CD19 CAR-T therapy could prolong OS and LFS and reduce the risk of relapse, with acceptable incidence rates for adverse events. More high-quality randomized controlled trials are needed to further determine the efficacy of HSCT.