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.

  • Correspondence
  • Published:

Influence of pretransplant inflammatory bowel disease on the outcome of allogeneic hematopoietic stem cell transplantation: a matched-pair analysis study from the Transplant Complications Working Party (TCWP) of the EBMT

Bone Marrow Transplantation volume 56, pages 3084–3087 (2021)Cite this article

Subjects

The use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been constantly increasing with the introduction of reduced-intensity conditioning (RIC) and alternative types of cell sources and donors. However, non-relapse-mortality (NRM), related mainly to graft-versus-host disease (GVHD), remains the major limitation for allo-HSCT, making its estimates important when considering this therapeutic approach. The most frequently used tool for making this prediction in clinical practice is the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) [1]. HCT-CI integrates 17 relevant pretransplant organ-specific comorbidities, among which is inflammatory bowel disease (IBD), comprised of Crohn’s disease and ulcerative colitis. The inclusion of IBD in HCT-CI is based on a Cox regression risk model which identified its association with increased NRM (Hazard ratio (HR), 1.3) and grade III-IV acute GVHD (HR, 1.6) [1, 2]. However, the only available formal analysis of NRM and GVHD risk in patients with IBD compared to matched controls failed to show any significant difference between the groups [3].

We therefore used the European Society for Blood and Marrow Transplantation (EBMT) dataset and designed a case-controlled analysis with the aim of assessing the outcomes of allo-HSCT in hematologic patients with and without prior IBD. The study included all EBMT registry patients age ≥ 18 years with known IBD who underwent a sibling or unrelated allo-HSCT between 2011 and 2015 for a hematologic malignancy. Patients with IBD were matched with three controls without any record of IBD before transplant, according to patient age, disease risk, intensity of conditioning, donor type and HLA disparity, Karnofsky score and GVHD prophylaxis. Cumulative incidence (CI) estimates of acute GVHD, chronic GVHD, relapse, and NRM were calculated with relapse or death from other causes defined as competitive events, using the Gray test for univariate analysis. Probabilities of overall survival (OS) and GVHD-free-relapse-free-survival (GRFS) were estimated using the Kaplan–Meier method, and the differences between groups were compared using the log-rank test. Multivariate analyses were performed using the Cox proportional-hazard model. In order to take into account correlation between cases and their controls, the multivariate Cox models included a cluster term for each quadruplet. Factors known to influence the outcomes were also included in the model: patient gender and year of transplantation.

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: Transplantation outcomes of the study population.

References

  1. Sorror ML, Maris MB, Storb RF, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.

    Article  CAS  Google Scholar 

  2. Sorror ML, Martin PJ, Storb RF, Bhatia S, Maziarz RT, Pulsipher MA, et al. Pretransplant comorbidities predict severity of acute graft-versus-host disease and subsequent mortality. Blood. 2014;124:287–95.

    Article  CAS  Google Scholar 

  3. Rabian F, Porcher R, Sicre de Fontbrune F, Lioure B, Laplace A, Nguyen S, et al. Influence of previous inflammatory bowel disease on the outcome of allogeneic hematopoietic stem cell transplantation: a matched-pair analysis. Biol Blood Marrow Transplant. 2016;22:1721–4.

    Article  Google Scholar 

  4. Nalle SC, Turner JR. Intestinal barrier loss as a critical pathogenic link between inflammatory bowel disease and graft-versus-host disease. Mucosal Immunol. 2015;8:720–30.

    Article  CAS  Google Scholar 

  5. Shono Y, van den Brink M. Gut microbiota injury in allogeneic haematopoietic stem cell transplantation. Nat Rev Cancer. 2018;18:283–95.

    Article  CAS  Google Scholar 

  6. Nishida A, Inoue R, Inatomi O, Bamba S, Naito Y, Andoh A. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol. 2018;11:1–10.

    Article  Google Scholar 

  7. Opazo M, Ortega-Rocha E, Corronado-Arrazola I, Bonifaz LC, Boudin, Neunlist M, et al. Intestinal microbiota influences non-intestinal related autoimmune diseases. Front Microbiol. 2018;9:432.

    Article  Google Scholar 

  8. Greco R, Labopin M, Badoglio M, Veys P, Furtado Silva JM, Abinun M, et al. Allogeneic HSCT for autoimmune disorders: a retrospective study from the EBMT, ADWP, IEWP and PDWP Working Parties. Front Immunol. 2019;10:1570.

    Article  CAS  Google Scholar 

  9. Snowden JA, Panes J, Alexander T, Allez M, Ardizzone S, Dierickx D, et al. Autologous hematopoietic stem cell transplantation (AHSCT) in severe Crohn’s disease: a review on behalf of ECCO and EBMT. J Crohns Colitis. 2018;12:476–88.

    Article  Google Scholar 

  10. Snowden JA, Hawkey C, Hind D, Swaby L, Mellor K, Emsley R, et al. Autologous stem cell transplantation in refractory Crohn’s disease—low intensity therapy evaluation (ASTIClite): study protocols for a multicentre, randomised controlled trial and observational follow up study. BMC Gastroenterol. 2019;19:82.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University Hospital Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia

    Zinaida Peric

  2. EBMT Paris Study Office, Department of Haematology, Saint Antoine Hospital, INSERM UMR 938, Sorbonne University, Paris, France

    Christophe Peczynski & Emmanuelle Polge

  3. University Hospital Eppendorf, Bone Marrow Transplantation Centre, Hamburg, Germany

    Nicolaus Kröger

  4. Bone Marrow Transplant Unit, National University Hospital, Rigshospitalet, Copenhagen, Denmark

    Henrik Sengeloev

  5. Medizinische Klinik u. Poliklinik V, University of Heidelberg, Heidelberg, Germany

    Aleksandar Radujkovic

  6. Silesian Medical Academy, Univ. Dept. of Haematology and BMT, Katowice, Poland

    Grzegorz Helbig

  7. Nottingham University, Nottingham, UK

    Nigel Russell

  8. Klinik fuer Innere Medzin III, Universitätsklinikum Ulm, Ulm, Germany

    Donald Bunjes

  9. Dept.of Hematology—BMT, Hopital St. Louis, Paris, France

    Gerard Socié

  10. GKT School of Medicine, Dept. of Haematological Medicine, King’s Denmark Hill Campus, London, UK

    Victoria Potter

  11. Dept. of Bone Marrow Transplantation, University Hospital, Essen, Germany

    Dietrich Beelen

  12. Department of Haematology, Addenbrookes Hospital, Cambridge, UK

    Charles Crawley

  13. Adult Leukaemia and Bone Marrow Transplant Unit, Christie NHS Trust Hospital, Manchester, UK

    Adrian Bloor

  14. Department of Medicine—Hematology, Oncology and Medical Faculty University Freiburg, University of Freiburg, Freiburg im Breisgau, Germany

    Jürgen Finke

  15. Department of Hematology, University Hospitals Leuven, KU Leuven, Leuven, Belgium

    Helene Schoemans

  16. Department of Hematology, Oncology and Tumorimmunology, Campus Virchow Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany

    Olaf Penack

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

    John A. Snowden

  18. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation and Institute of Immunology, Hannover, Germany

    Christian Koenecke

  19. Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warszawa, Poland

    Grzegorz W. Basak

Authors
  1. Zinaida Peric
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christophe Peczynski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emmanuelle Polge
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicolaus Kröger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henrik Sengeloev
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aleksandar Radujkovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Grzegorz Helbig
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nigel Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Donald Bunjes
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gerard Socié
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Victoria Potter
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Dietrich Beelen
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Charles Crawley
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Adrian Bloor
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Jürgen Finke
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Helene Schoemans
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Olaf Penack
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. John A. Snowden
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Christian Koenecke
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Grzegorz W. Basak
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ZP assembled and analyzed data and wrote the first version of the paper. CK, HS, OP, and GB designed the study, supervised research, analyzed data, and helped with writing the paper. EP and CP assembled the data, performed statistical analysis, and commented on the paper. All other co-authors collected data, recruited patients, and helped with writing the paper. All authors approved submission of the paper for publication.

Corresponding author

Correspondence to Zinaida Peric.

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peric, Z., Peczynski, C., Polge, E. et al. Influence of pretransplant inflammatory bowel disease on the outcome of allogeneic hematopoietic stem cell transplantation: a matched-pair analysis study from the Transplant Complications Working Party (TCWP) of the EBMT. Bone Marrow Transplant 56, 3084–3087 (2021). https://doi.org/10.1038/s41409-021-01458-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-021-01458-9

This article is cited by

Search

Advanced search

Quick links