Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT

Bone Marrow Transplantation volume 58, pages 881–892 (2023)Cite this article

Subjects

Abstract

We previously analyzed trends in incidence and factors associated with lethal complications in ALL/AML/CML patients (causes of deaths; COD-1 study). The objective of this study was the analysis of incidence and specific causes of death after HCT, with focus on infectious deaths in two time periods, 1980–2001 (cohort-1) and 2002–2015 (cohort-2). All patients with HCT for lymphoma, plasma cell disorders, chronic leukemia (except CML), myelodysplastic/myeloproliferative disorders, registered in the EBMT-ProMISe-database were included (n = 232,618) (COD-2 study). Results were compared to those in the ALL/AML/CML COD-1 study. Mortality from bacterial, viral, fungal, and parasitic infections decreased in very early, early and intermediate phases. In the late phase, mortality from bacterial infections increased, while mortality from fungal, viral, or unknown infectious etiology did not change. This pattern was similar for allo- and auto-HCT in COD-1 and COD-2 studies, with a distinct and constant lower incidence of all types of infections at all phases, after auto-HCT. In conclusion, infections were the main cause of death before day +100, followed by relapse. Mortality from infectious deaths significantly decreased, except late phase. Post-transplant mortality has significantly decreased in all phases, from all causes after auto-HCT; it has decreased in all phases after allo-HCT except late phase.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Cumulative incidences of mortality after HCT over four post-transplant phases and from cohort 1 to cohort 2.
Fig. 2: Changes over time of deaths after HCT by post-transplant period (1 = cohort 1980-2001; 2 = cohort 2002-2015).

Similar content being viewed by others

References

  1. Styczynski J, Tridello G, Koster L, Iacobelli S, van Biezen A, van der Werf S. et al. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transpl. 2020;55:126–36. https://doi.org/10.1038/s41409-019-0624-z.

    Article  Google Scholar 

  2. Holmqvist AS, Chen Y, Wu J, Battles K, Francisco L, Hageman L. et al. Late Mortality after Allogeneic Bone Marrow Transplantation in Childhood for Bone Marrow Failure Syndromes and Severe Aplastic Anemia. Biol Blood Marrow Transpl. 2019;25:749–55. https://doi.org/10.1016/j.bbmt.2018.12.063.

    Article  Google Scholar 

  3. Norkin M, Shaw BE, Brazauskas R, Tecca HR, Leather HL, Gea-Banacloche J. et al. Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2019;25:362–8. https://doi.org/10.1016/j.bbmt.2018.09.031.

    Article  Google Scholar 

  4. Gratwohl A, Brand R, Frassoni F, Rocha V, Niederwieser D, Reusser P. et al. Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time. Bone Marrow Transpl. 2005;36:757–69. https://doi.org/10.1038/sj.bmt.1705140.

    Article  CAS  Google Scholar 

  5. Hahn T, Sucheston-Campbell LE, Preus L, Zhu X, Hansen JA, Martin PJ. et al. Establishment of Definitions and Review Process for Consistent Adjudication of Cause-specific Mortality after Allogeneic Unrelated-donor Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2015;21:1679–86. https://doi.org/10.1016/j.bbmt.2015.05.019.

    Article  Google Scholar 

  6. Copelan E, Casper JT, Carter SL, van Burik JA, Hurd D, Mendizabal AM. et al. A scheme for defining cause of death and its application in the T cell depletion trial. Biol Blood Marrow Transpl. 2007;13:1469–76. https://doi.org/10.1016/j.bbmt.2007.08.047.

    Article  Google Scholar 

  7. Gratwohl A, Sureda A, Cornelissen J, Apperley J, Dreger P, Duarte R. et al. Alloreactivity: the Janus-face of hematopoietic stem cell transplantation. Leukemia. 2017;31:1752–9. https://doi.org/10.1038/leu.2017.79.

    Article  CAS  PubMed  Google Scholar 

  8. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.

    Article  CAS  PubMed  Google Scholar 

  9. Gratwohl A, Sureda A, Baldomero H, Gratwohl M, Dreger P, Kröger N, et al. Economics and Outcome After Hematopoietic StemCell Transplantation: A Retrospective Cohort Study. EBioMedicine. 2015;2:2101–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Iacobelli S. Suggestions on the use of statistical methodologies in studies of the European Group for Blood and Marrow Transplantation. Bone Marrow Transpl. 2013;48:S1–37. https://doi.org/10.1038/bmt.2012.282.

    Article  Google Scholar 

  11. Klein JP, Moeschberger ML. Survival analysis: techniques for censored and truncated data. New York: Springer-Verlag; 2003.

  12. Gratwohl A, Pasquini MC, Aljurf M, Atsuta Y, Baldomero H, Foeken L. et al. One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol. 2015;2:e91–100. https://doi.org/10.1016/S2352-3026(15)00028-9.

    Article  PubMed  Google Scholar 

  13. Niederwieser D, Baldomero H, Bazuaye N, Bupp C, Chaudhri N, Corbacioglu S. et al. One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors. Haematologica. 2022;107:1045–53. https://doi.org/10.3324/haematol.2021.279189.

    Article  PubMed  Google Scholar 

  14. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M. et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N. Engl J Med. 2010;363:2091–101. https://doi.org/10.1056/NEJMoa1004383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Meyers JD, Bowden RA, Counts GW. Infectious complications of marrow transplant: risk factors for infection. Prog Clin Biol Res. 1989;309:357–66.

    CAS  PubMed  Google Scholar 

  16. Styczynski J, Piekarska A, Zaucha-Prażmo A, Zaucha JM, Zając-Spychała O, Wróbel T. et al. Antimicrobial prophylaxis in adults and children undergoing hematopoietic cell transplantation: 2021 Polish recommendations. Acta Haematol Pol. 2021;52:528–42. https://doi.org/10.5603/AHP.a2021.0097.

    Article  Google Scholar 

  17. Gratwohl A, Brand R, McGrath E, van Biezen A, Sureda A, Ljungman P. et al. Use of the quality management system “JACIE” and outcome after hematopoietic stem cell transplantation. Haematologica. 2014;99:908–15. https://doi.org/10.3324/haematol.2013.096461.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 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 

Download references

Acknowledgements

The authors acknowledge the cooperation of the participating teams and their staff. They acknowledge the excellent work of the EBMT and IDWP Leiden Study Unit.

Author information

Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Torun, Bydgoszcz, Poland

    Jan Styczynski

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

    Gloria Tridello & Simone Cesaro

  3. EBMT Leiden Study Unit, Leiden, The Netherlands

    Gloria Tridello, Linda Koster, Nina Knelange, Lotus Wendel, Anja van Biezen & Steffie van der Werf

  4. Division of Infectious Diseases, University of Genoa (DISSAL) and Ospedale Policlinico San Martino, Genoa, Italy

    Malgorzata Mikulska

  5. Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland

    Lidia Gil

  6. Hôpital Henri Mondor, Assistance Publique-Hopitaux de Paris (AP-HP) and Paris-Est-Créteil University, Creteil, France

    Catherine Cordonnier

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

    Per Ljungman

  8. Faculty of Medicine, Hebrew University of Jerusalem, Pediatric Infectious Diseases, Hadassah Medical Center, Jerusalem, Israel

    Diana Averbuch

  9. EBMT Activity Survey Office, Hematology, Department of Medicine, University Hospital, Basel, Switzerland

    Helen Baldomero

  10. Institut Paoli Calmettes Comprehensive Cancer Center and Inserm CBT-1409, Centre d’Investigations Cliniques en Biothérapies, Marseille, France

    Christian Chabannon

  11. Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany

    Selim Corbacioglu

  12. Laboratory of Hematology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

    Harry Dolstra

  13. Klinik für Hämatologie und Stammzelltransplantation, HELIOS Klinikum Berlin-Buch, Berlin, Germany

    Bertram Glass

  14. Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy

    Raffaella Greco

  15. Department of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany

    Nicolaus Kröger

  16. BMT Unit, Department of Hematology, Hospital St. Louis, Paris, France

    Régis Peffault de Latour

  17. Department of Hematology, Hospital Saint Antoine, Sorbonne University, INSERM UMRs938, Paris, France

    Mohamad Mohty

  18. Pediatric Immune-Hematology Unit, Necker Children Hospital, Assistance Publique Hôpitaux de Paris, Paris, France

    Benedicte Neven

  19. School of Medicine, University of Zagreb, University Hospital Center Zagreb, Zagreb, Croatia

    Zinaida Peric

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

    John A. Snowden

  21. Clinical Hematology Department, Institut Català d’Oncologia-Hospitalet, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), University of Barcelona, Barcelona, Spain

    Anna Sureda

  22. CHU de Lille, Université de Lille, INSERM U1286, Infinite, Lille, France

    Ibrahim Yakoub-Agha

  23. Hematology Department, Hospital de la Princesa, Madrid, Spain

    Rafael de la Camara

Authors
  1. Jan Styczynski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gloria Tridello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Linda Koster
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nina Knelange
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lotus Wendel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anja van Biezen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Steffie van der Werf
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Malgorzata Mikulska
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lidia Gil
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Catherine Cordonnier
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Per Ljungman
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Diana Averbuch
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Simone Cesaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Helen Baldomero
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Christian Chabannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Selim Corbacioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Harry Dolstra
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Bertram Glass
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Raffaella Greco
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Nicolaus Kröger
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Régis Peffault de Latour
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Mohamad Mohty
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Benedicte Neven
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Zinaida Peric
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. John A. Snowden
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Anna Sureda
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Ibrahim Yakoub-Agha
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Rafael de la Camara
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JSt and GT designed the study and drafted the manuscript. LK, AvB, SvW, and HB were responsible for the data collection and assembly. GT conducted the statistical analysis. MM, LG, CC, PL, DA, SC, CC, SCo, HD, BG, RG, NK, RPL, MM, BN, ZP, JAS, AS, IYA, and RC were responsible for the integrity of the data and gave scientific input. All authors have seen and approved the final version.

Corresponding author

Correspondence to Jan Styczynski.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Styczynski, J., Tridello, G., Koster, L. et al. Decrease of lethal infectious complications in the context of causes of death (COD) after hematopoietic cell transplantation: COD-2 and COD-1 study of the Infectious Diseases Working Party EBMT. Bone Marrow Transplant 58, 881–892 (2023). https://doi.org/10.1038/s41409-023-01998-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-023-01998-2

This article is cited by

Search

Advanced search

Quick links