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Prophylactic versus Preemptive modified donor lymphocyte infusion for high-risk acute leukemia after allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study

Bone Marrow Transplantation volume 59, pages 85–92 (2024)Cite this article

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Abstract

Donor lymphocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely used in preventing post-transplant relapse. We conducted this study to compare the superiority of prophylactic modified DLI (pro-DLI) and preemptive modified DLI (pre-DLI) in patients with high-risk relapse features acute leukemia. Pro-DLI was performed in 95 patients, whereas the pre-DLI cohort included 176 patients. In the pre-DLI cohort, 42 patients relapsed without chance for pre-DLI while 95 patients remained CR without detectable minimal residual disease (MRD). Thirty-nine patients in the pre-DLI cohort became minimal MRD positive/mixed chimerism and received pre-DLI. Pro-DLI cohort had higher 3-year progression-free-survival (PFS) (63.4%vs.53.0%, P = 0.026) and overall survival (OS) (65.2% vs. 57.0%, P = 0.14) compared to the pre-DLI cohort. The 3-year cumulative incidence of relapse (CIR) was 25.3% in the pro-DLI cohort which was significantly lower than 36.7% in the pre-DLI cohort (P = 0.02). The cumulative incidence of grade III-IV aGVHD, cGVHD and non-relapse mortality were comparable between cohorts. Multivariable analysis demonstrated strong protective effect of pro-DLI on OS (hazard ratio (HR) = 0.63, P = 0.04), PFS (HR = 0.54, P = 0.005) and CIR (HR = 0.50, P = 0.005). In high-risk patients with acute leukemia, early scheduled pro-DLI rather than pre-DLI after detectable MRD would reduce post-transplant relapse and improve long-term survival.

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Fig. 1: Flow diagram showing patient selection.
Fig. 2: Cumulative incidence of GVHD.
Fig. 3: Cumulative incidence of relapse, NRM, and probability of surivial.

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All data supporting this article are provided in the manuscript (Tables 1 and 2; Figs. 1,2 and 3).

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Acknowledgements

This work was supported by grants from The National Natural Science Foundation of China [grant numbers 81970158, 82170205, 82000180] and Pediatric Leukemia Diagnostic and Therapeutic Technology Research Center of Zhejiang Province [JBZX-201904].

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Author notes

  1. These authors contributed equally: Luxin Yang, Xiaoyu Lai, Ting Yang.

  2. These authors jointly supervised this work: He Huang, Yi Luo.

Authors and Affiliations

  1. Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Luxin Yang, Xiaoyu Lai, Lizhen Liu, Jimin Shi, Yanmin Zhao, Yibo Wu, Jian Yu, Yongxian Hu, Yamin Tan, Yishan Ye, Zhen Cai, He Huang & Yi Luo

  2. Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou, 311121, China

    Luxin Yang, Xiaoyu Lai, Lizhen Liu, Jimin Shi, Yanmin Zhao, Yibo Wu, Jian Yu, Haowen Xiao, Yongxian Hu, Yamin Tan, Yishan Ye, Zhen Cai, He Huang & Yi Luo

  3. Institute of Hematology, Zhejiang University, Hangzhou, China

    Luxin Yang, Xiaoyu Lai, Lizhen Liu, Jimin Shi, Yanmin Zhao, Yibo Wu, Jian Yu, Haowen Xiao, Yongxian Hu, Yamin Tan, Yishan Ye, Zhen Cai, He Huang & Yi Luo

  4. Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, China

    Luxin Yang, Xiaoyu Lai, Lizhen Liu, Jimin Shi, Yanmin Zhao, Yibo Wu, Jian Yu, Yongxian Hu, Yamin Tan, Yishan Ye, Zhen Cai, He Huang & Yi Luo

  5. Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, China

    Ting Yang & Jinhua Ren

  6. Department of Hematology, The First Afliated Hospital of Fujian Medical University, Fuzhou, 350005, China

    Ting Yang

  7. The affiliated people’s hospital of Ningbo University, Ningbo, China

    Ying Lu & Junjie Cao

  8. The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Yi Chen

  9. Department of Hematology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Haowen Xiao

  10. Ningbo City First Hospital, Ningbo, China

    Guifang Ouyang

  11. Children’s Hospital Zhejiang University, School of Medicine, Hangzhou, China

    Weiqun Xu

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  1. Luxin Yang
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Contributions

L.Y. and Y.L. designed the research; L.Y., X.Y., T.Y., Y.L., L.L., J.S., C.Y., and H.X. enrolled and treated patients. L.Y., X.Y., and T.Y. analyzed the data and wrote the manuscript; and all authors provided patient data and gave final approval for the manuscript. The authors declare no competing financial interests.

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Correspondence to He Huang or Yi Luo.

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Yang, L., Lai, X., Yang, T. et al. Prophylactic versus Preemptive modified donor lymphocyte infusion for high-risk acute leukemia after allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study. Bone Marrow Transplant 59, 85–92 (2024). https://doi.org/10.1038/s41409-023-02137-7

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