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Adenovirus infections after allogeneic hematopoietic cell transplantation in children and adults: a study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Bone Marrow Transplantation volume 59, pages 1402–1412 (2024)Cite this article

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Abstract

The objective of the study was the analysis of clinical types, outcomes, and risk factors associated with the outcome of adenovirus (ADV) infection, in children and adults after allo-HCT. A total number of 2529 patients (43.9% children; 56.1% adults) transplanted between 2000 and 2022 reported to the EBMT database with diagnosis of ADV infection were analyzed. ADV infection manifested mainly as viremia (62.6%) or gastrointestinal infection (17.9%). The risk of 1-year mortality was higher in adults (p = 0.0001), and in patients with ADV infection developing before day +100 (p < 0.0001). The 100-day overall survival after diagnosis of ADV infections was 79.2% in children and 71.9% in adults (p < 0.0001). Factors contributing to increased risk of death by day +100 in multivariate analysis, in children: CMV seropositivity of donor and/or recipient (p = 0.02), and Lansky/Karnofsky score <90 (p < 0.0001), while in adults: type of ADV infection (viremia or pneumonia vs gastrointestinal infection) (p = 0.0004), second or higher HCT (p = 0.0003), and shorter time from allo-HCT to ADV infection (p = 0.003). In conclusion, we have shown that in patients infected with ADV, short-term survival is better in children than adults. Factors directly related to ADV infection (time, clinical type) contribute to mortality in adults, while pre-transplant factors (CMV serostatus, Lansky/Karnofsky score) contribute to mortality in children.

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Fig. 1: Survival probability.

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Data availability

Data represent the results of registry-based study of patients with documented ADV infection. No personal data are included. With the retrospective registry-based design of the study, no ethical review board approval was necessary. The data set remains the property of EBMT. It can be available upon reasonable request to the corresponding author.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, University Hospital, Collegium Medicum UMK, Bydgoszcz, Poland

    Jan Styczynski

  2. Department of Medical Statistics & Bioinformatics, EBMT Data Office, Leiden, The Netherlands

    Gloria Tridello, Nina Knelange & Lotus Wendel

  3. Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska Comprehensive Cancer Center, Departments of Medicine Huddinge and Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet Stockholm, Stockholm, Sweden

    Per Ljungman & Stephan Mielke

  4. Division of Infectious Diseases, Department of Health Sciences (DISSAL), University of Genova, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Malgorzata Mikulska

  5. Department of Hematology, Poznan University of Medical Sciences, Poznan, Poland

    Lidia Gil

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

    Simone Cesaro

  7. Faculty of Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel

    Diana Averbuch

  8. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    Peter von dem Borne

  9. Department of Hematology, BMT, Hopital St. Louis, Paris, France

    Aliénor Xhaard

  10. Unité d’Immunologie et d’Hématologie, Hôpital Necker, Paris, France

    Benedicte Neven

  11. Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK

    John A. Snowden

  12. Pediatric Hematology and Immunology Department, Hôpital Robert Debre, Paris, France

    Jean-Hugues Dalle

  13. Department of Hematology, Hopital d’Enfants, Vandoeuvre_Nancy, France

    Marie Thérèse Rubio

  14. Department of Hematology, Addenbrookes Hospital, Cambridge, UK

    Charles Crawley

  15. Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium

    Johan Maertens

  16. Department of Hematology, University Medical Centre, Utrecht, The Netherlands

    Jurgen Kuball

  17. Department D’Hematologie, CHU Nantes, Nantes, France

    Patrice Chevallier

  18. Département Hématologie Oncologie Pédiatrique, Hopital d’Enfants de la Timone, CHU, Marseille, France

    Gérard Michel

  19. Oncology Unit, The Children’s Hospital at Westmead, Sydney, Australia

    Melissa Gabriel

  20. University Hospital Birmingham NHS Trust, Birmingham, UK

    David Burns

  21. Department of Pediatric Hematology, Bone Marrow Unit, Central Manchester NHS Trust, Manchester, UK

    Robert F. Wynn

  22. Institut d’Hematologie et d’Oncologie Pediatrique, Lyon, France

    Cecile Renard

  23. Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands

    Nicole Blijlevens

  24. Onco-Hématologie Pédiatrique, CHU Bordeaux Groupe Hospitalier Pellegrin-Enfants, Bordeaux, France

    Charlotte Jubert

  25. Department of Hematology, Section for Stem Cell Transplantation, Oslo University Hospital, Rikshospitalet, Clinic for Cancer Medicine, Oslo, Norway

    Tobias Gedde-Dahl

  26. Northern Centre for Bone Marrow Transplantation, Newcastle, UK

    Matthew Collin

  27. Centre Hospitalier Lyon Sud, Lyon, France

    Helene Labussiere-Wallet

  28. Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, 50-556, Wroclaw, Poland

    Krzysztof Kalwak

  29. Erasmus MC Cancer Institute, Rotterdam, The Netherlands

    Annoek E. C. Broers

  30. CHU de Lille, Université de Lille, Lille, France

    Ibrahim Yakoub-Agha

  31. TD7 (Stem Cell Transplant Unit), Turku University Hospital, Turku, Finland

    Maija Itäla-Remes

  32. Hospital de la Princesa, Madrid, Spain

    Rafael de la Camara

Authors
  1. Jan Styczynski
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  2. Gloria Tridello
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  3. Nina Knelange
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  4. Lotus Wendel
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  5. Per Ljungman
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  6. Malgorzata Mikulska
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  11. Aliénor Xhaard
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  12. Stephan Mielke
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  13. Benedicte Neven
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  14. John A. Snowden
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  15. Jean-Hugues Dalle
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  16. Marie Thérèse Rubio
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  17. Charles Crawley
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  18. Johan Maertens
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  19. Jurgen Kuball
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  20. Patrice Chevallier
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  21. Gérard Michel
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  22. Melissa Gabriel
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  23. David Burns
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  24. Robert F. Wynn
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  25. Cecile Renard
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  26. Nicole Blijlevens
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  27. Charlotte Jubert
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  28. Tobias Gedde-Dahl
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  29. Matthew Collin
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  30. Helene Labussiere-Wallet
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  31. Krzysztof Kalwak
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  32. Annoek E. C. Broers
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  33. Ibrahim Yakoub-Agha
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  34. Maija Itäla-Remes
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  35. Rafael de la Camara
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Contributions

JS, MM – design of the study; NK, LW, GT – preparing database; GT – statistical analysis, tables, and figures; JS – writing manuscript; JS, MM, DA, SC, LG, PL, RdlC – analysis and critical revision of the paper; all authors – providing clinical data, revision, and final approval of the paper.

Corresponding author

Correspondence to Jan Styczynski.

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Competing interests

MM reports lecture fees and board meeting fees from Allovir, bioMérieux, Gilead, Janssen, Moderna, Mundipharma, Pfizer, all outside the submitted work. JAS declares consultancy for Medac, Jazz, Vertex, and Kiadis Pharma in previous 24 months. All other authors declared no conflict of interest.

Ethics approval and consent to participate

The study was conducted in accordance with the EBMT Guidelines for Retrospective Studies and the principles of the Declaration of Helsinki. EBMT centres commit to obtain informed consent with the local regulations applicable at the time of transplantation in order to report pseudoanonymised data to the EBMT.

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Styczynski, J., Tridello, G., Knelange, N. et al. Adenovirus infections after allogeneic hematopoietic cell transplantation in children and adults: a study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant 59, 1402–1412 (2024). https://doi.org/10.1038/s41409-024-02361-9

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