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Human cytomegalovirus-specific T-cell responses and immune-guided strategies as predictors of clinically significant infection in hematopoietic stem cell transplant recipients after letermovir prophylaxis

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Fig. 1: HCMV-specific T-cell response measured at the end of prophylaxis in Controllers (CTR) and Non-controllers (Non-CTR).

Data availability

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

References

  1. Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377:2433–44. https://doi.org/10.1056/NEJMoa1706640.

    Article  CAS  PubMed  Google Scholar 

  2. Li CR, Greenberg PD, Gilbert MJ, Goodrich JM, Riddell SR. Recovery of HLA-restricted cytomegalovirus (CMV)-specific T-cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis. Blood. 1994;83:1971–9.

    Article  CAS  PubMed  Google Scholar 

  3. Hakki M, Riddell SR, Storek J, Carter RA, Stevens-Ayers T, Sudour P, et al. Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation. Blood. 2003;102:3060–7. https://doi.org/10.1182/blood-2002-11-3472.

    Article  CAS  PubMed  Google Scholar 

  4. Gabanti E, Borsani O, Caldera D, Colombo AA, Ferretti VV, Alessandrino EP, et al. Early T cell reconstitution and cytokine profile may help to guide a personalized management of human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. J Clin Virol. 2021;135:104734. https://doi.org/10.1016/j.jtct.2022.01.008.

    Article  CAS  PubMed  Google Scholar 

  5. Zavaglio F, Vitello D, Bergami F, Arena F, Borsani O, Colombo AA, et al. Human Cytomegalovirus (HCMV) - specific T-cell response after letermovir prophylaxis is predictive for subsequent HCMV reactivation in haematopoietic stem cell transplant recipients. J Clin Virol. 2023;165:105519. https://doi.org/10.1016/j.jcv.2023.105519.

    Article  CAS  PubMed  Google Scholar 

  6. Wagner-Drouet E, Teschner D, Wolschke C, Janson D, Schäfer-Eckart K, Gärtner J, et al. Standardized monitoring of cytomegalovirus-specific immunity can improve risk stratification of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation. Haematologica. 2021;106:363–74. https://doi.org/10.3324/haematol.2019.229252.

    Article  CAS  PubMed  Google Scholar 

  7. Lee H, Park KH, Ryu JH, Choi AR, Yu JH, Lim J, et al. Cytomegalovirus (CMV) immune monitoring with ELISPOT and QuantiFERON-CMV assay in seropositive kidney transplant recipients. PLoS One. 2017;12:e0189488. https://doi.org/10.1371/journal.pone.0189488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ruan Y, Guo W, Liang S, Xu Z, Niu T. Diagnostic performance of cytomegalovirus (CMV) immune monitoring with ELISPOT and QuantiFERON-CMV assay in kidney transplantation: a PRISMA-compliant article. Medicine. 2019;98:e15228. https://doi.org/10.1097/MD.0000000000015228.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gabanti E, Bruno F, Scaramuzzi L, Mangione F, Zelini P, Gerna G, et al. Predictive value of human cytomegalovirus (HCMV) T-cell response in the control of HCMV infection by seropositive solid-organ transplant recipients according to different assays and stimuli. N Microbiol. 2016;39:247–25.

    CAS  Google Scholar 

  10. Gabanti E, Lilleri D, Ripamonti F, Bruno F, Zelini P, Furione M, et al. Reconstitution of human cytomegalovirus-specific CD4+ T cells is critical for control of virus reactivation in hematopoietic stem cell transplant recipients but does not prevent organ infection. Biol Blood Marrow Transplant. 2005;21:2192–202. https://doi.org/10.1016/j.bbmt.2015.08.002.

    Article  CAS  Google Scholar 

  11. Vyas A, Raval AD, Kamat S, LaPlante K, Tang Y, Chemaly RF. Real-world outcomes associated with letermovir use for cytomegalovirus primary prophylaxis in allogeneic hematopoietic cell transplant recipients: a systematic review and meta-analysis of observational studies. Open Forum Infect Dis. 2022;10:ofac687. https://doi.org/10.1093/ofid/ofac687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Russo D, Schmitt M, Pilorge S, Stelljes M, Kawakita T, Teal VL, et al. Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2024;11:e127–e135. https://doi.org/10.1016/S2352-3026(23)00344-7.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank the nurses of the Haematology Division for obtaining the patient samples and Daniela Sartori for manuscript editing.

Funding

Ministero della Salute, Ricerca Corrente (grant no. 08075023) and Ricerca Finalizzata (grant no. RF-2019-12370797).

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Authors and Affiliations

Authors

Contributions

FB and IC supervised the team, obtained funding and had leadership responsibility for the research activity planning and execution. DL and DM provided substantial contributions to the conception and design of the study, acquisition, analysis and interpretation of data, and revised the manuscript critically for important intellectual content. FZ, GG and EI contributed to the acquisition, analysis and validation of data. MM, VZ, GV, AB, ID and NP enrolled patients, collected and managed the data. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Irene Cassaniti.

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Competing interests

The authors declare no competing interests.

Ethics approval

All participants provided written informed consent. The study was approved by the local Ethics Committee (Comitato Etico Area Pavia) and the Institutional Review Board (Proc. 2022-3.11/451).

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Mele, D., Malagola, M., Zavaglio, F. et al. Human cytomegalovirus-specific T-cell responses and immune-guided strategies as predictors of clinically significant infection in hematopoietic stem cell transplant recipients after letermovir prophylaxis. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-025-02788-8

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