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CAR19/22 T cell cocktail therapy for B-ALL relapsed after allogeneic hematopoietic stem cell transplantation

  • Author Footnotes
    # N. Yan and N. Wang contributed equally to this work.
    Nan Yan
    Footnotes
    # N. Yan and N. Wang contributed equally to this work.
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
    Search for articles by this author
  • Author Footnotes
    # N. Yan and N. Wang contributed equally to this work.
    Na Wang
    Footnotes
    # N. Yan and N. Wang contributed equally to this work.
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Gaoxiang Wang
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Liang Huang
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Chunrui Li
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Di Wang
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Jue Wang
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Lifang Huang
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Fankai Meng
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
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  • Jia Wei
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Liting Chen
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Xia Mao
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Jianfeng Zhou
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
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  • Yicheng Zhang
    Correspondence
    Corresponding author: Dr. Yicheng Zhang and Dr. Yang Cao, Huazhong University of Science and Technology, Department of Hematology, Tongji Hospital, Tongji Medical College, 1095 Jiefang Avenue, Wuhan, Hubei, China
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Yang Cao
    Correspondence
    Corresponding author: Dr. Yicheng Zhang and Dr. Yang Cao, Huazhong University of Science and Technology, Department of Hematology, Tongji Hospital, Tongji Medical College, 1095 Jiefang Avenue, Wuhan, Hubei, China
    Affiliations
    Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China
    Search for articles by this author
  • Author Footnotes
    # N. Yan and N. Wang contributed equally to this work.

      ABSTRACT

      B cell acute lymphocytic leukemia (B-ALL) patients who have relapsed after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, and there is currently no standard approach available. Chimeric antigen receptor (CAR)-T cells induce high rates of initial response and long-term remission among patients with B-cell malignancies, especially B-ALL. Meanwhile, sequential infusion of CAR19/22 T cells has been proven to be effective at preventing tumor immune escape. In the present study, we retrospectively analyzed 23 B-ALL patients who relapsed after allogeneic (allo)-HSCT and underwent sequential infusion of CAR19/22 T cells, including nine donor-derived and 14 recipient-derived, in our center from July 2016 to July 2020, to evaluate the safety and efficacy of the cocktail of two single-specific CAR-T cells in B-ALL patients relapsed after transplantation. Except for one patient refusing evaluation, the remaining 22 patients achieved minimal residual disease (MRD)-negative complete remission within 30 days after CAR-T infusion. Most toxicities were slight and reversible. The estimated 12-month progression-free survival (PFS) rate was 59.2% (95% confidence interval [CI], 35.9% to 76.5%), and the estimated 12-month overall survival (OS) rate was 67.4% (95% CI, 43.2% to 83.1%). Only two patients had CD19-negative recurrence. In addition, early recurrence after transplantation, graft-versus-host disease (GVHD) and severe infection after CAR-T infusion were poor prognostic factors. Our results indicate that sequential infusion of CAR19/22 T cells is safe and effective for relapsed ALL patients after HSCT. This trial was registered at www.chictr.org.cn as #ChiCTR-OPN-16008526.

      Keywords

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