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Increased Epstein-Barr virus reactivation but similar incidence of post-transplant lymphoproliferative disorders due to pre-emptive rituximab therapy following allogeneic hematopoietic stem cell transplantation in the letermovir era for cytomegalovirus prophylaxis

Bone Marrow Transplantation volume 60, pages 721–724 (2025)Cite this article

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The Epstein-Barr virus (EBV) infects about 85% of the global population [1]. In immunocompetent individuals, EBV remains symptom-free, controlled by EBV-specific T cells [2]. However, after allogeneic hematopoietic stem cell transplantation (allo-HSCT), EBV may be reactivated due to immune suppression, potentially progressing to severe conditions like EBV-associated post-transplant lymphoproliferative disorders (EBV-PTLD) [3]. Despite advancements in earlier diagnosis and treatment, the mortality rate of EBV-PTLD remains high [4].

Risk factors for EBV reactivation and EBV-PTLD include reduced-intensity conditioning, human leukocyte antigen (HLA)-mismatched or unrelated donors, cord blood transplantation, graft-versus-host disease (GVHD), splenectomy, T-cell depletion, anti-thymocyte globulins (ATG), age, delayed T cell reconstitution and others [3, 5, 6]. These factors overlap with those for cytomegalovirus (CMV) reactivation. Recently, the use of letermovir (LTV) has significantly reduced CMV reactivation [7]. Although LTV lacks intrinsic activity against EBV, it may affect immune reconstitution by reducing CMV antigenic stimulation. Several studies have reported higher rates of EBV reactivation in patients receiving LTV prophylaxis after haploidentical HSCT or umbilical cord blood transplantation [8,9,10]. This study analyzed the incidence of EBV-related complications within 200 days post-transplant, comparing individuals who received prophylactic LTV with those who did not.

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Fig. 1: Comparison of EBV Reactivation and Related Outcomes Between LTV and Non-LTV Groups.

Data availability

The data supporting the results of this study can be obtained by reaching out to the corresponding author.

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Funding

Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-017; 2023-I2M-2-007, 2021-I2M-1-060), National Natural Sciences Foundation of China (82470208), National Key R&D Program of China (2024YFC2510500), Beijing Xisike Clinical Oncology Research Foundation (Y-SYBLD2022RWR-0017).

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Author notes

  1. These authors contributed equally: Sisi Zhen, Li Liu, Xiaoyu Zhang.

Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Hematopoietic Stem Cell Transplantation Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, PR China

    Sisi Zhen, Li Liu, Xiaoyu Zhang, Jieru Wang, Jiali Sun, Chen Liang, Wenbin Cao, Jialin Wei, Weihua Zhai, Xin Chen, Qiaoling Ma, Rongli Zhang, Donglin Yang, Yi He, Aiming Pang, Mingzhe Han, Erlie Jiang & Sizhou Feng

  2. Tianjin Institutes of Health Science, Tianjin, PR China

    Sisi Zhen, Li Liu, Xiaoyu Zhang, Jieru Wang, Jiali Sun, Chen Liang, Wenbin Cao, Jialin Wei, Weihua Zhai, Xin Chen, Qiaoling Ma, Rongli Zhang, Donglin Yang, Yi He, Aiming Pang, Mingzhe Han, Erlie Jiang & Sizhou Feng

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Contributions

SF and EJ were responsible for the design of the study. SZ, LL, and XZ carried out the data analysis and prepared the initial manuscript draft. JW, CL, WC, JW, WZ, XC, QM, RZ, DY, YH, AP, and M.H collected the data. JW. and JS provided some guidance on data analysis. SF and JS provided the funding acquisition. SF and EJ supplied resources, supervision, review and editing. Every author examined the manuscript and consented to the final version.

Corresponding authors

Correspondence to Erlie Jiang or Sizhou Feng.

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Ethics approval and consent to participate

This study was approved by the Institutional Review Board and Ethics Committee of the Institute of Hematology and Blood Diseases Hospital. The ethics committee approved the waiver of informed consent owing to the retrospective nature of the review. All human data of patients’ records were confirmed for collection in accordance with the relevant guidelines and regulations.

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The authors declare no competing interests.

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Zhen, S., Liu, L., Zhang, X. et al. Increased Epstein-Barr virus reactivation but similar incidence of post-transplant lymphoproliferative disorders due to pre-emptive rituximab therapy following allogeneic hematopoietic stem cell transplantation in the letermovir era for cytomegalovirus prophylaxis. Bone Marrow Transplant 60, 721–724 (2025). https://doi.org/10.1038/s41409-025-02542-0

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