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Superiority of preemptive donor lymphocyte infusion based on minimal residual disease in acute leukemia patients after allogeneic hematopoietic stem cell transplantation

Authors

  • Yamin Tan,

    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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    • YT and KD contributed equally to this work
  • Kaili Du,

    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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    • YT and KD contributed equally to this work
  • Yi Luo,

    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Jimin Shi,

    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Ling Cao,

    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Yanlong Zheng,

    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Gaofeng Zheng,

    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Yanmin Zhao,

    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Xiujing Ye,

    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • Zhen Cai,

    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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  • He Huang

    Corresponding author
    1. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
    • Address reprint requests to: He Huang, MD, PhD, Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University, School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, China; e-mail: hehuang.zju@gmail.com.

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  • This project was supported by grants from the National High Technology Research and Development Program of China (2012AA020905), the Major Technology Program (Key Social Development) of the Science Technology Department of Zhejiang Province (2012C13021-1), Natural Science Foundation of Zhejiang Province, China (No. Y2110127), and the Science and Technology Planning Project of Zhejiang Province (No. 2010KYA075).

Abstract

Background

Donor lymphocyte infusion (DLI) was used as salvage therapy in leukemia relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but existing results on DLI administration to acute leukemia patients were disappointing. Although increasing minimal residual disease (MRD) after HSCT had been proven to be highly indicative of posttransplant relapse, preemptive DLI (pDLI) based on MRD has not been well evaluated.

Study Design and Methods

We retrospectively analyzed 70 acute leukemia patients after allo-HSCT in our center between January 2005 and December 2010. Sixteen patients received pDLIs based on increasing MRD results (pDLI group), and 11 relapsed patients received therapeutic DLIs with or without chemotherapy (tDLI group). Donor lymphocytes were collected from the original donors without stimulation and infused without further manipulation. The median mononuclear cell doses and CD3+ cell doses were 1.49 × 108 and 5.51 × 107/kg. Forty-three patients who did not receive pDLI therapy after detecting increasing MRD (no pDLI group) were also included as a comparison.

Results

The response rate was 100% in the pDLI group, whereas it was 63.6% in the tDLI group (p = 0.019). Survival outcomes were superior in the pDLI group compared with the tDLI group (χ2 = 14.624, p = 0.000); estimated overall survival (OS) at 1 year was 93.8% with pDLI and 27.3% with tDLI. The incidence of overall acute graft-versus-host disease (aGVHD) and Grade III to IV aGVHD was higher in the pDLI group but with no significance. Patients in the “no pDLI” group showed an inferior prognosis with 1-year OS at 65.1% (95% confidence interval, 50.8%-79.4%).

Conclusion

Our results demonstrated the efficacy and safety of pDLI and suggested that pDLI based on MRD monitoring was superior in acute leukemia patients with potential progression compared with salvage DLI administrated in overt relapse.

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