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Donor-derived CAR-T therapy improves the survival of relapsed B-ALL after allogeneic transplantation compared with donor lymphocyte infusion

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Abstract

Chimeric antigen receptor (CAR)-T cell therapy revolutionized treatment for various hematologic malignances. However, limited studies were reported to compare the efficacy and safety of CAR-T and donor lymphocyte infusion (DLI) for patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after hematopoietic stem cell transplantation (HSCT) comprehensively. We conducted a single-center, retrospective comparative study that consisted of 12 patients who were treated with DLI (control group) and 12 patients treated with donor-derived CD19 CAR-T cells (experimental group, 6 patients also received CD22 or CD123 CAR-T cells sequentially) with 3 overlaps. The event-free survival (EFS) of patients in experimental group was superior to that of the control group: 516 days versus 98 days (p = 0.0415). Compared with 7 of 12 patients treated with DLI suffered grades III–IV acute graft versus host disease (aGVHD), one grade III aGVHD developed in patients treated with CAR-T therapy. No significant difference in the incidence of infection was identified between these two groups. Most patients in the experimental group had only mild cytokine release syndrome and none developed neurotoxicity. The univariate analysis of patients in the experiment group revealed that earlier CAR-T therapy for post-transplantation relapse was associated with better EFS. There was no significant difference in EFS between patients treated with dual-target CAR-T with those with single CD19 CAR-T. In this study, our data supported that donor-derived CAR-T therapy is a safe and potentially effective treatment for relapsed B-ALL after HSCT and may be superior to DLI.

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Data availability

The data that support the findings of this study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank all members of the study team, the patients and their families.

Funding

This work was supported by the Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR110105014); the National Natural Science Foundation of China (U2001224); the Science and Technology Program of Guangzhou, China (202201011041); Medical Scientific Research Foundation of Guangdong Province, China (A2021052).

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Author notes

  1. Zhao Liang and Hong Xu have equally contributed to this work.

Authors and Affiliations

  1. Department of Hematology, Zhujiang Hospital, Southern Medical University, No. 253, Industrial Avenue, Guangzhou, Guangdong, China

    Zhao Liang, Hong Xu, Xuan Zhou, JiLong Yang, Sanfang Tu, Yanjie He, Lijuan Zhou & Yuhua Li

  2. Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China

    Yuhua Li

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  1. Zhao Liang
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Contributions

HX collected data, performed analysis and wrote the manuscript. ZL designed the study and revised the manuscript. SFT and YJH took part in the registration of clinical research. ZL, XZ and JLY contributed to patient management. LJZ contributed to data collection. YHL conceived the project, designed the study and revised the manuscript.

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Correspondence to Yuhua Li.

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The authors declare that they have no competing interests.

Ethics approval and consent to participate

The study protocol was approved by the Ethics Committee of Zhujiang Hospital, Southern Medical University (No.2016-XYNK-002, No.2017-XYNK-001).

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Liang, Z., Xu, H., Zhou, X. et al. Donor-derived CAR-T therapy improves the survival of relapsed B-ALL after allogeneic transplantation compared with donor lymphocyte infusion. Human Cell 36, 1716–1728 (2023). https://doi.org/10.1007/s13577-023-00934-2

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