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Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation
Yifei Cheng, Yuhong Chen, Chenhua Yan, Yu Wang, Xiangyu Zhao, Yao Chen, Wei Han, Lanping Xu, Xiaohui Zhang, Kaiyan Liu, Shasha Wang, Lungji Chang, Lei Xiao, Xiaojun Huang
Engineering ›› 2019, Vol. 5 ›› Issue (1) : 150-155.
PDF(352 KB)
PDF(352 KB)
Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation
Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with B-ALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT); furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.
Donor-derived CD19-targeted T cell infusion / Hematopoietic stem cell transplantation / B cell acute lymphoblastic leukemia / Minimal residual disease
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This work was supported by the Scientific Research Foundation for Capital Medicine Development (2018-2-4084).
Yifei Cheng and Yuhong Chen analyzed the material and wrote the paper. Shasha Wang collected the data. Xiangyu Zhao, Chenhua Yan, Yu Wang, Yao Chen, Wei Han, Lanping Xu, and Xiaohui Zhang performed the research. Lungji Chang and Lei Xiao contributed to cell production. Kaiyan Liu designed the research. Xiaojun Huang designed the research and edited the manuscript.
The present protocol was evaluated and allowed by the Peking University People’s Hospital review board. All enrolled patients gave informed consent in accordance with the Declaration of Helsinki.
Yifei Cheng, Yuhong Chen, Chenhua Yan, Yu Wang, Xiangyu Zhao, Yao Chen, Wei Han, Lanping Xu, Xiaohui Zhang, Kaiyan Liu, Shasha Wang, Lungji Chang, Lei Xiao, and Xiaojun Huang declare that they have no conflict of interest or financial conflicts to disclose.
| aGVHD | acute graft-versus-host disease |
|---|---|
| allo-HSCT | allogeneic hematopoietic stem cell transplantation |
| ALT | elevated alanine transaminase |
| B-ALL | B cell acute lymphoblastic leukemia |
| Bu | busulfan |
| CAR | chimeric antigen receptor |
| CART19 | CD19-directed chimeric antigen receptor-modified T cell |
| CD | cluster of differentiation |
| CIR | cumulative incidence of relapse |
| CR | complete remission |
| CRS | cytokine release syndrome |
| CsA | cyclosporine A |
| Cy | cyclophosphamide |
| DLI | donor lymphoblastic infusion |
| EFS | event-free survival |
| FACS | fluorescence-activated cell-sorting |
| GVHD | graft-versus-host disease |
| GVL | graft-versus-leukemia |
| haplo-HSCT | haploidentical hematopoietic stem cell transplantation |
| HLA | human leukocyte antigen |
| HSCT | hematopoietic stem cell transplantation |
| LFS | leukemia-free survival |
| MRD | minimal residual disease |
| MTX | methotrexate |
| OS | overall survival |
| PBMC | peripheral blood mononuclear cell |
| qPCR | quantitative real-time polymerase chain reaction |
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