Frontiers in Oncology (Apr 2021)

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

  • Xinjie Xu,
  • Xinjie Xu,
  • Xinjie Xu,
  • Sifei Chen,
  • Sifei Chen,
  • Zijing Zhao,
  • Zijing Zhao,
  • Xinyi Xiao,
  • Xinyi Xiao,
  • Shengkang Huang,
  • Shengkang Huang,
  • Zhaochang Huo,
  • Yuhua Li,
  • Sanfang Tu

DOI
https://doi.org/10.3389/fonc.2021.651944
Journal volume & issue
Vol. 11

Abstract

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BackgroundThis 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).MethodsThe 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.ResultsWe 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).ConclusionsCompared 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.

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