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.

Post-Transplant Complications

An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation

Bone Marrow Transplantation volume 30, pages 441–446 (2002)Cite this article

Abstract

We monitored levels of C-reactive protein (CRP) in 96 consecutive adult allogeneic BMT patients (age 15–50 years) transplanted in our unit. Major transplant-related complications (MTC) occurred in 32% of cases and included: hepatic veno-occlusive disease, pneumonitis, severe endothelial leakage syndrome and >II acute GVHD. Transplant-related mortality (TRM) before day 100 post-BMT was 13.5%. Variables included in a stepwise logistic regression model were: gender, age, disease category, donor type, T cell depletion, TBI, use of growth factors, bacteremia, mean CRP-levels >50 mg/l between days 0 and 5 (CRP day 0–5) and >100 mg/l between days 6 and 10 (CRP day 6–10) post-BMT. Only high CRP-levels (for MTC and TRM) (P < 0.001) and donor-type (for TRM) (P = 0.02) were independent risk factors. The estimated probability for MTC was 73% (CRP day 6–10 >100 mg/l) vs 17% (CRP day 6–10 <100 mg/l). Using the same cut-off levels, the probabilities for TRM were 36.5% vs 1% in the identical sibling donor situation and 88% vs 12.5% in other donor-type transplants. We conclude that the degree of systemic inflammation, as reflected by CRP-levels, during the first 5–10 days after BMT identifies patients at risk of MTC and TRM. Our data may be useful in selecting patients for clinical trials involving pre-emptive anti-inflammatory treatment.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

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

Figure 1
Figure 2

References

  1. Gratwohl A, Hermans J, Goldman JM et al. Risk assessment for patients with chronic myeloid leukemia before allogeneic blood or marrow transplantation Lancet 1998 352: 1087 1092

    Article  CAS  PubMed  Google Scholar 

  2. Marmont AM, Horowitz MM, Gale RP et al. T-cell depletion of HLA-identical transplants in leukemia Blood 1991 78: 2120 2130

    CAS  PubMed  Google Scholar 

  3. Nash RA, Pepe MS, Storb R et al. Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporin and methotrexate Blood 1992 80: 1838 1845

    CAS  PubMed  Google Scholar 

  4. Holler E, Roncarolo MG, Hintermeier-Knabe R et al. Prognostic significance of increased IL-10 production in patients prior to allogeneic bone marrow transplantation Bone Marrow Transplant 2000 25: 237 241

    Article  CAS  PubMed  Google Scholar 

  5. Remberger M, Ringden O, Markling L . TNF-alpha levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD Bone Marrow Transplant 1995 15: 99 104

    CAS  PubMed  Google Scholar 

  6. Bacigalupo A, Oneto R, Bruno B et al. Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin Bone Marrow Transplant 1999 24: 653 659

    Article  CAS  PubMed  Google Scholar 

  7. Gabay C, Kushner I . Acute-phase proteins and other systemic responses to inflammation New Engl J Med 1999 340: 448 454

    Article  CAS  PubMed  Google Scholar 

  8. Schots R, Kaufman L, Van Riet I et al. Monitoring of C-reactive protein after allogeneic bone marrow transplantation identifies patients at risk of severe transplant-related complications and mortality Bone Marrow Transplant 1998 22: 79 85

    Article  CAS  PubMed  Google Scholar 

  9. McDonald GB, Hinds MS, Fisher LD et al. Veno-occlusive disease of the liver and multi-organ failure after bone marrow transplantation: a cohort study of 355 patients Ann Intern Med 1993 118: 255 267

    Article  CAS  PubMed  Google Scholar 

  10. Storb R, Thomas ED . Graft-versus-host disease in dog and man: the Seattle experience Immunol Rev 1985 88: 215 238

    Article  CAS  PubMed  Google Scholar 

  11. Holler E, Kolb HJ, Moller A et al. Increased serum levels of tumor necrosis factor-alpha precede major complications of bone marrow transplantation Blood 1990 75: 1011 1016

    CAS  PubMed  Google Scholar 

  12. Vachino G, Gelfand JA, Atkins MB et al. Complement activation in cancer patients undergoing immunotherapy with interleukin-2 (IL-2): binding of complement and C-reactive protein by IL-2- activated lymphocytes Blood 1991 78: 2505 2513

    CAS  PubMed  Google Scholar 

  13. Arber C, Passweg JR, Fluckiger U et al. C-reactive protein and fever in neutropenic patients Scand J Infect Dis 2000 32: 515 520

    Article  CAS  PubMed  Google Scholar 

  14. Schots R, Trullemans F, Van Riet I et al. The clinical impact of early gram-positive bacteremia and the use of vancomycin after allogeneic bone marrow transplantation Transplantation 2000 69: 1511 1514

    Article  CAS  PubMed  Google Scholar 

  15. Castell JV, Gomez-Lechon MJ, David M et al. Acute-phase response of human hepatocytes: regulation of acute-phase protein synthesis by interleukin-6 Hepatology 1990 12: 1179 1186

    Article  CAS  PubMed  Google Scholar 

  16. Antin J, Ferrera J . Cytokine dysregulation and acute graft-versus-host disease Blood 1992 80: 2964 2968

    CAS  PubMed  Google Scholar 

  17. Gugliotta L, Catani L, Vianelli N et al. High plasma levels of tumor necrosis factor-alpha may be predictive of veno-occlusive disease in bone marrow transplantation Blood 1994 83: 2385 2386

    CAS  PubMed  Google Scholar 

  18. Schots R, Van Riet I, Ben Othman T et al. A systemic inflammatory response involving C-reactive protein, interleukin-6, interleukin-8 and tumor-necrosis factor-alpha contributes to the development of hepatic veno-occlusive disease after allogeneic bone marrow transplantation Blood 2001 98: (Suppl. 1) 195a (Abstr. 816)

    Google Scholar 

  19. Bearman SI . The syndrome of hepatic veno-occlusive disease after marrow transplantation Blood 1995 11: 3005 3020

    Google Scholar 

  20. Khoury H, Adkins D, Brown R et al. Does early treatment with high-dose methylprednisone alter the course of hepatic regimen-related toxicity? Bone Marrow Transplant 2000 25: 737 743

    Article  CAS  PubMed  Google Scholar 

  21. Chopra R, Eaton JD, Grassi A et al. Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study Br J Haematol 2000 111: 1122 1129

    Article  CAS  PubMed  Google Scholar 

  22. Bernard GR, Vincent JL, Laterre PF et al. Efficacy and safety of recombinant human activated protein C for severe sepsis New Engl J Med 2001 344: 699 709

    Article  CAS  PubMed  Google Scholar 

  23. Hervé P, Flesh M, Tiberghien P et al. Phase I–II trial of a monoclonal anti-tumor necrosis factor alpha antibody for the treatment of refractory severe acute graft-versus-host disease Blood 1992 79: 3362 3368

    PubMed  Google Scholar 

  24. Holler E, Kolb HJ, Mittermuller J et al. Modulation of acute graft-versus-host-disease after allogeneic bone marrow transplantation by tumor necrosis factor-alpha (TNF alpha) release in the course of pretransplant conditioning: role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human TNF alpha (MAK 195F) Blood 1995 86: 890 899

    CAS  PubMed  Google Scholar 

  25. Racadot E, Milpied N, Bordigoni P et al. Sequential use of three monoclonal antibodies in corticosteroid-resistent acute GVHD: a multicentric pilot study including 15 patients Bone Marrow Transplant 1995 15: 669 677

    CAS  PubMed  Google Scholar 

  26. Verbon A, Dekkers PE, ten Hove T et al. IC14, an anti-CD14 antibody, inhibits endotoxin-mediated symptoms and inflammatory responses in humans J Immunol 2001 166: 3599 3605

    Article  CAS  PubMed  Google Scholar 

  27. Hill GR, Crawford JM, Cooke KR et al. Total body irradiation and acute graft-versus-host disease: the role of gastro-intestinal damage and inflammatory cytokines Blood 1997 90: 3204 3213

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Mrs A Willekens and her nursing staff from the BMT-Unit for the excellent care of our patients. This work was supported by grant from the scientific Fund W Gepts AZ-VUB.

Author information

Authors and Affiliations

  1. BMT Unit, Academisch Ziekenhuis-Vrije Universiteit Brussel, Brussels, Belgium

    R Schots, I Van Riet, F Trullemans, M De Waele & B Van Camp

  2. Centre de Greffe de Moelle Osseuse, Tunis, Tunisia

    T Ben Othman

  3. Department of Medical Statistics, Academisch Ziekenhuis-Vrije Universiteit Brussel, Brussels, Belgium

    L Kaufman

Authors
  1. R Schots
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I Van Riet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Ben Othman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F Trullemans
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M De Waele
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B Van Camp
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L Kaufman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Schots, R., Van Riet, I., Ben Othman, T. et al. An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major complications and 100-day transplant-related mortality after allogeneic bone marrow transplantation. Bone Marrow Transplant 30, 441–446 (2002). https://doi.org/10.1038/sj.bmt.1703672

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703672

Keywords

  • C-reactive protein
  • severe complications
  • transplant-related mortality
  • allogeneic BMT

This article is cited by

Search

Advanced search

Quick links