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Treatment of Epstein–Barr virus associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation with intrathecal donor lymphocyte infusion

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective measure for the treatment of hematological disease. With the progress and widespread use of allo-HSCT, Epstein–Barr virus (EBV) related central nervous system (CNS) diseases have gotten more and more attention because of its poor prognosis and overall survival. Since currently there is no standard treatment for patients with EBV-associated CNS diseases and reported therapies are heterogeneous with mixed results, we attempted to develop a novel therapeutic method. We applied a regimen of intrathecal donor lymphocyte infusion (IDLI) in three patients with EBV-associated CNS diseases after allo-HSCT in addition to immunosuppressants reduction and combined antiviral therapy. All of three patients were responsive to this therapy: all clinical symptoms and EBV load in CSF were resolved 10, 17, and 12 days after initial IDLI, respectively, and magnetic resonance imaging (MRI) showed that lesions of case 1 and 2 disappeared 15 and 19 days after initial IDLI, respectively. Even more appealing, there were no acute or chronic adverse reactions during the infusion and up to 23 months of follow-up. In conclusion, IDLI seems to be an effective and safe method for EBV-associated CNS diseases in allo-HSCT recipients. We recommend this treatment modality for further investigation.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China(Grant N0.81470827). The authors thank for every faculty member of Department of Hematology of the Affiliated Cancer Hospital of Zhengzhou University who had participant in the study.

Author contributions

Jian Zhou, Yongping Song, Yanli Zhang, Quande Lin, Baijun Fang and Juanjuan Zhao designed the research. Juanjuan Zhao, Yingling Zu, Lijie Han, Ruirui Gui, Fengkuan Yu, acquired the clinical data. Juanjuan Zhao, Zhen Li, and Huifang Zhao analyzed data and wrote the manuscript. Jian Zhou and Yongping Song supervised the study.

Funding

This study was funded by National Nature Science Foundation of China (grant number 81470827).

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Correspondence to Jian Zhou or Yongping Song.

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The authors declare that they have no conflict of interest.

Clinical responsibilities and informed consent

We conducted thoroughly comprehensive communication with three patients and their families to get them informed of the possible efficacy and adverse reactions of this procedure. Informed consent was obtained from individual participants (Cases 1 and 3) or their guardians (Case 2). The patients and/or their families take full responsibilities for any problem resulting from this procedure.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Zhao, J., Zu, Y., Han, L. et al. Treatment of Epstein–Barr virus associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation with intrathecal donor lymphocyte infusion. Bone Marrow Transplant 54, 821–827 (2019). https://doi.org/10.1038/s41409-018-0409-9

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