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Letermovir for Cytomegalovirus infection in pediatric patients undergoing allogenic hematopoietic stem cell transplantation: a real-life study by the Infectious Diseases Working Group of Italian Association of Pediatric Hematology-Oncology (AIEOP)

Bone Marrow Transplantation volume 59, pages 505–512 (2024)Cite this article

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Abstract

Letermovir prophylaxis revolutionized the approach to Cytomegalovirus infection in adult hematopoietic stem cell transplant (HCT), while data in pediatric setting are still lacking. We retrospectively analyzed 87 HCT children transplanted in 11 AIEOP centers receiving letermovir as off-label indication between January 2020 and November 2022. Letermovir was used as primary, secondary prophylaxis or CMV treatment in 39, 26 and 22 cases, respectively; no discontinuation due to toxicity was reported. Median duration was 100 days (14-256) for primary and 96 days (8-271) for secondary prophylaxis, respectively. None of the patients experienced CMV-clinically significant reactivation during Letermovir primary prophylaxis; one patient developed breakthrough infection during secondary prophylaxis, and 10 and 1 patient experienced asymptomatic CMV-reactivation and CMV-primary infection after drug discontinuation, respectively. Median duration of letermovir in CMV treatment was 40 days (7-134), with 4/22 patients suffering CMV-pneumonia, with an overall response rate of 86.4%. With a median follow-up of 10.7 months (8.2-11.8), estimated 1-year overall survival was 86%; no CMV-related deaths were reported in prophylaxis groups. This is the largest report on Letermovir use in pediatric HCT; real-life data confirm an excellent toxicity profile, with high efficacy as CMV prophylaxis; results in CMV-infection treatment should be investigated in larger, prospective trials.

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Fig. 1: Overall survival and cumulative incidence of breakthrough infections.

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The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all members of the Infectious Diseases Working Group (IDWG) of the Associazione Italiana di Oncologia e Ematologia Pediatrica (AIEOP) and their collaborators for their contribution to this report.

Funding

The authors declare no sources of funding.

Author information

Author notes

  1. These authors contributed equally: Federica Galaverna, Francesco Baccelli.

Authors and Affiliations

  1. Department of Pediatric Oncology, Hematology, Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy

    Federica Galaverna, Francesco Quagliarella, Daria Pagliara & Franco Locatelli

  2. Department of Medical and surgical sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy

    Francesco Baccelli, Daniele Zama & Riccardo Masetti

  3. Pediatric Emergency Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

    Daniele Zama

  4. Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy

    Gloria Tridello, Alice Giacomazzi & Simone Cesaro

  5. Pediatric Hematology and Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

    Riccardo Masetti

  6. Pediatric Oncohematology and Bone marrow transplant Unit, ASST Spedali Civili, Brescia, Italy

    Elena Soncini

  7. Pediatric Hematology Oncology, Azienda Ospedaliera Brotzu, Cagliari, Italy

    Rossella Mura

  8. Pediatric Immunohematology Unit and bone marrow transplant Unit, IRCCS Ospedale San Raffaele, Milano, Italy

    Federica Barzaghi

  9. Department of Pediatrics, Fondazione MBBM - Ospedale San Gerardo, Monza, Italy

    Antonella Colombini & Giulia Prunotto

  10. Unità Operativa di Trapianto di Cellule Staminali Ematopoietiche e Terapie Cellulari, AORN Santobono-Pausilipon, Napoli, Italy

    Maria Rosaria D’Amico

  11. Pediatric Hematology, Oncology and Stem Cell Transplant Division, Department of Women’s and Children’s Health, University Hospital of Padova, Padova, Italy

    Elisabetta Calore & Alessandra Biffi

  12. Pediatric Oncology Hematology, Ospedale Santa Maria della Misericordia, Perugia, Italy

    Katia Perruccio

  13. Department of Pediatrics, Azienda Unità Sanitaria Locale di Rimini, Rimini, Italy

    Pietro Gasperini

  14. Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milano, Italy

    Chiara Oltolini

  15. Catholic University of the Sacred Heart, Roma, Italy

    Franco Locatelli

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  1. Federica Galaverna
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Contributions

GF and BF contributed to design the study, collected data and wrote the paper; ZD collected data and revised the manuscript; MR, SE, MR, BF, CA, PG, DMR, CE, BA, PK, GP, OC, QF, and GA collected data; PD and LF supervised the project and revised the manuscript; CS conceived the study, collected the data, wrote, read, and supervised the manuscript.

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Correspondence to Federica Galaverna.

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Galaverna, F., Baccelli, F., Zama, D. et al. Letermovir for Cytomegalovirus infection in pediatric patients undergoing allogenic hematopoietic stem cell transplantation: a real-life study by the Infectious Diseases Working Group of Italian Association of Pediatric Hematology-Oncology (AIEOP). Bone Marrow Transplant 59, 505–512 (2024). https://doi.org/10.1038/s41409-024-02209-2

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