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CD19-targeted chimeric antigen receptor-modified T cells induce remission in patients with relapsed acute B lymphoblastic leukemia after umbilical cord blood transplantation
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  • Qianwen Xu,
  • Hui Xu,
  • Lei Xue,
  • Min Wang,
  • Guifang Pan,
  • Xuhan Zhang,
  • Kaidi Song,
  • Wen Yao,
  • Xiang Wan,
  • Juan Tong,
  • Huilan Liu,
  • Hanying Xu,
  • Xin Liu,
  • Xiao-yu Zhu,
  • Zi-min Sun,
  • Lin Yang,
  • Xing-bing Wang
Qianwen Xu
Anhui Medical University
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Hui Xu
The First Affiliated Hospital of USTC
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Lei Xue
The First Affiliated Hospital of USTC
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Min Wang
PersonGen-Anke Cellular Therapeutics Co., Ltd.
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Guifang Pan
PersonGen-Anke Cellular Therapeutics Co., Ltd.
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Xuhan Zhang
The First Affiliated Hospital of USTC
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Kaidi Song
The First Affiliated Hospital of USTC
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Wen Yao
The First Affiliated Hospital of USTC
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Xiang Wan
The First Affiliated Hospital of USTC
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Juan Tong
The First Affiliated Hospital of USTC
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Huilan Liu
The First Affiliated Hospital of USTC
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Hanying Xu
PersonGen-Anke Cellular Therapeutics Co., Ltd.
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Xin Liu
The First Affiliated Hospital of USTC
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Xiao-yu Zhu
The First Affiliated Hospital of USTC
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Zi-min Sun
The First Affiliated Hospital of USTC
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Lin Yang
PersonGen-Anke Cellular Therapeutics Co., Ltd.
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Xing-bing Wang
Anhui Medical University
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Abstract

Background Few therapies are available for treating patients with B acute lymphoblastic leukemia (B-ALL) who relapse after umbilical cord blood transplant (UCBT). Chimeric antigen receptor (CAR)-modified T cell therapy targeting CD19 is novel and effective for treating refractory/relapsed (R/R) hematological malignancies. Method We report the response rate, toxicity, and survival of CD19-targeted CAR modified T cells administered to 10 patients with B-ALL who relapsed after UCBT from April 2018 to September 2019. Patients ≥14 years of age were subsequently recruited in the clinical trial (NCT02851589) conducted at the First Affiliated Hospital of USTC, Hefei, China. Results Patients (n = 11) were infused with peripheral blood T cells transduced with CD19-directed CAR lentiviral vectors (0.42 × 106 –3.91 × 106 cells/kg body weight). Among 10 patients who were successfully infused, 9 achieved minimal residual disease-negative complete remission (MRD-neg CR). As of July 30, 2020, 6 of 10 patients experienced a relapse (median follow-up for CR was 13.2 months, range 5.8–31.7 months). The 6-month rates of progression-free survival (PFS) and overall survival (OS) were 44.4% and 77.8%, respectively. Toxicities were reversible, including severe cytokine release syndrome (CRS) (≥ grade 3) and neurotoxicity in 10% (1/10) and 10% (1/10) of patients, respectively, and no patient experienced graft-versus-host disease (GVHD). Conclusion CD19-targeted CAR-modified T cell therapy may therefore serve as a safe and effective approach for treating patients with relapsed B-ALL after UCBT. A multicenter clinical trial including more subjects is required to confirm safety and efficacy.

Peer review status:Published

06 May 2021Published in Chinese Medical Journal volume Publish Ahead of Print. 10.1097/CM9.0000000000001491