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ACUTE LYMPHOBLASTIC LEUKEMIA

Preemptive donor-derived anti-CD19 CAR T-cell infusion showed a promising anti-leukemia effect against relapse in MRD-positive B-ALL after allogeneic hematopoietic stem cell transplantation

Leukemia volume 36, pages 267–270 (2022)Cite this article

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most effective methods to cure adult B-ALL patients [1, 2]. However, some patients still face the problem of recurrence post-HSCT, and the outcomes are poor. Positive minimal residual disease (MRD+) after transplantation is highly indicative of recurrence [3, 4]. Donor lymphocyte infusion (DLI) is a common preemptive intervention that can clear MRD and prevent relapse [5,6,7]. However, there are some limitations to DLI, such as severe GVHD and myelosuppression [6]. More importantly, some patients showed persistent MRD+ after preemptive interventions, and relapse was inevitable.

Chimeric antigen receptor (CAR) T-cell infusion is effective adoptive cell therapy. The successes of CAR T-cell therapy in patients with B-ALL or lymphomas revolutionized anti-leukemia therapy, providing a potential therapeutic option for patients who are refractory to standard chemotherapy [8, 9]. In addition, previous studies have reported that the treatment of relapsed B-ALL after transplantation with donor-derived CAR T-cells is safe with a high remission rate and acceptable relapse rate [6, 10,11,12,13,14]. For MRD+ B-ALL patients who showed no response to DLI after allo-HSCT, our pilot study observed that all of them were MRD negative after CAR T-cell therapy, and no severe side effects were observed [15], indicating that MRD+ B-ALL patients after allo-HSCT may benefit from CAR T-cell therapy. However, no prospective study has identified the efficacy and safety of CAR T-cell therapy as a preemptive treatment for MRD+ B-ALL patients after allo-HSCT. In addition, whether CAR T-therapy is superior to traditional DLI therapy in MRD+ patients after transplantation remains unclear.

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Fig. 1: Cytokines release and surviva after donor-derived CAR T-cell infusion in MRD+ patients after allo-HSCT.

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Acknowledgements

We are grateful to all the patients who participated in our exploratory clinical studies. We thank ImmunoChina Pharmaceuticals (Beijing, China) and Cellular Biomedicine Group Ltd. (Shanghai, China) for their help in organizing the clinical-grade expansion of the CAR T-cells. This work was supported by the National Key Research and Development Program of China (No. 2017YFA0104500), the Scientific Research Foundation for Capital Medicine Development (No. 2018-2-4084), the Innovative Research Groups of the National Natural Science Foundation of China (No. 81621001), the Beijing Municipal Science & Technology Commission (No. Z171100001017098), the Peking University Clinical Scientist Program (No. BMU2019LCKXJ003), the Clinical Medicine Plus X-Young Scholars Project of Peking University (No. PKU2020LCXQ015) supported by “the Fundamental Research Funds for the Central Universities”, and the Peking University People’s Hospital Research and Development Funds (No. RDX2019-14).

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  1. These authors contributed equally: Xiang-Yu Zhao, Zheng-Li Xu.

Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

    Xiang-Yu Zhao, Zheng-Li Xu, Xiao-Dong Mo, Yu-Hong Chen, Meng Lv, Yi-Fei Cheng, Huan Chen, Ying-Jun Chang, Lan-Ping Xu, Yu Wang, Xiao-Hui Zhang, Kai-Yan Liu & Xiao-Jun Huang

  2. Peking-Tsinghua Center for Life Sciences, Beijing, China

    Xiao-Jun Huang

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Contributions

Contribution: X-YZ and X-JH conceived and designed the research; X-YZ, Z-LX, Y-HC, ML, HC, Y-FC, YW, L-PX, X-HZ, K-YL, X-JH performed the experiments and collected and analyzed the data; X-YZ, X-DM, and X-JH wrote the manuscript; and all authors revised and approved the manuscript.

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Correspondence to Xiao-Jun Huang.

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Zhao, XY., Xu, ZL., Mo, XD. et al. Preemptive donor-derived anti-CD19 CAR T-cell infusion showed a promising anti-leukemia effect against relapse in MRD-positive B-ALL after allogeneic hematopoietic stem cell transplantation. Leukemia 36, 267–270 (2022). https://doi.org/10.1038/s41375-021-01351-w

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