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.

  • Original Article
  • Published:

Graft-versus-Host Disease

Risk factors for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: retrospective analysis of 73 patients who received cyclosporin A

Bone Marrow Transplantation volume 40, pages 875–880 (2007)Cite this article

Abstract

Cyclosporin A (CsA) has been used most widely as an immunosuppressive agent for preventing graft-versus-host disease (GVHD). To explore the risk factors including CsA blood levels for grades II–IV acute GVHD, we retrospectively analyzed the data of patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital between March 1989 and July 2001. Seventy-three patients (47 males and 26 females) received CsA and short-term methotrexate for GVHD prophylaxis. CsA 1.5 mg/kg was administered as a 3-h infusion twice daily from day 1 until the patient recovered from the toxic gastrointestinal complication. Methotrexate was given at a dose of 15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6 and 11. Grades II–IV acute GVHD occurred in 18 patients (24.7%). Multivariate Cox regression analysis revealed that higher C5 (the whole-blood CsA concentration at 5 h after the start of infusion) before the onset of acute GVHD reduced the onset of grades II–IV acute GVHD with a hazard ratio of 0.994 (95% confidence interval 0.989–0.999) for every increase of 1 ng/ml. Our data indicate that inadequate exposures of CsA can be a vital risk for developing acute GVHD. From our results, we consider that precise monitoring of CsA concentrations and adjustment of CsA dose using the concentration may be effective to prevent the onset of severe acute GVHD. To confirm this finding, further prospective study will be needed.

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Devergie A . Graft vs. host disease. In: Apperley J, Carreras E, Gluckman E, Gratwohl A, Masszi T (eds). Haemopoietic Stem Cell Transplantation. European School of Hematology: Paris, 2004, pp 163–176.

    Google Scholar 

  2. Yee GC, Self SG, McGuire TR, Carlin J, Sanders JE, Deeg HJ . Serum cyclosporine concentration and risk of acute graft-versus-host disease after allogeneic marrow transplantation. N Engl J Med 1988; 319: 65–70.

    Article  CAS  PubMed  Google Scholar 

  3. Nash RA, Pepe MS, Storb R, Longton G, Pettinger M, Anasetti C et al. Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Blood 1992; 80: 1838–1845.

    CAS  PubMed  Google Scholar 

  4. Martin P, Bleyzac N, Souillet G, Galambrun C, Bertrand Y, Maire PH et al. Relationship between CsA trough blood concentration and severity of acute graft-versus-host disease after paediatric stem cell transplantation from matched-sibling or unrelated donors. Bone Marrow Transplant 2003; 32: 777–784.

    Article  CAS  PubMed  Google Scholar 

  5. Martin P, Bleyzac N, Souillet G, Galambrun C, Bertrand Y, Maire PH et al. Clinical and pharmacological risk factors for acute graft-versus-host disease after paediatric bone marrow transplantation from matched-sibling or unrelated donors. Bone Marrow Transplant 2003; 32: 881–887.

    Article  CAS  PubMed  Google Scholar 

  6. Ogawa N, Kanda Y, Matsubara M, Asano Y, Nakagawa M, Sakata-Yanagimoto M et al. Increased incidence of acute graft-versus-host disease with the continuous infusion of cyclosporine A compared to twice-daily infusion. Bone Marrow Transplant 2004; 33: 549–552.

    Article  CAS  PubMed  Google Scholar 

  7. Sato N, Furukawa T, Kuroha T, Hashimoto S, Masuko M, Takahashi H et al. High-dose cytosine arabinoside and etoposide with total body irradiation as a preparatory regimen for allogeneic hematopoietic stem-cell transplantation in patients with acute lymphoblastic leukemia. Bone Marrow Transplant 2004; 34: 299–303.

    Article  CAS  PubMed  Google Scholar 

  8. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  9. Schran HF, Rosano TG, Hassell AE, Pell MA . Determination of cyclosporine concentrations with monoclonal antibodies. Clin Chem 1987; 33: 2225–2229.

    CAS  PubMed  Google Scholar 

  10. Lindholm A, Napoli K, Rutzky L, Kahan BD . Specific monoclonal radioimmunoassay and fluorescence polarization immunoassay for trough concentration and area-under-the-curve monitoring of cyclosporine in renal transplantation. Ther Drug Monit 1992; 14: 292–300.

    Article  CAS  PubMed  Google Scholar 

  11. Halloran P . Calcineurin inhibition-relationship to cyclosporine blood concentration. Focus Med 1998; 13: 15–18.

    Google Scholar 

  12. Kahan BD . Therapeutic drug monitoring of cyclosporine: 20 years of progress. Transplant Proc 2004; 36: 378S–391S.

    Article  CAS  PubMed  Google Scholar 

  13. Nashan B, Cole E, Levy G, Thervet E . Clinical validation studies of Neoral C(2) monitoring: a review. Transplantation 2002; 73: S3–S11.

    Article  PubMed  Google Scholar 

  14. Levy G, Thervet E, Lake J, Uchida K, Consensus on Neoral C(2): Expert Review in Transplantation (CONCERT) Group. Patient management by Neoral C(2) monitoring: an international consensus statement. Transplantation 2002; 73: S12–S18.

    Article  PubMed  Google Scholar 

  15. Duncan N, Craddock C . Optimizing the use of cyclosporin in allogeneic stem cell transplantation. Bone Marrow Transplant 2006; 38: 169–174.

    Article  CAS  PubMed  Google Scholar 

  16. Ruutu T, Niederwieser D, Gratwohl A, Apperley JF . A survey of the prophylaxis and treatment of acute GVHD in Europe: a report of the European Group for Blood and Marrow, Transplantation (EBMT). Chronic leukaemia working party of the EBMT. Bone Marrow Transplant 1997; 19: 759–764.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Miyako Baba and Yoko Tanahashi, Clinical Laboratory Division, Niigata University Medical and Dental Hospital for their excellent technical assistance and helpful discussion.

Author information

Authors and Affiliations

  1. Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    N Izumi, K Okazuka, N Tsukada, T Abe, T Yano, T Kurasaki, K Toba & Y Aizawa

  2. Division of Bone Marrow Transplantation, Niigata University Medical and Dental Hospital, Niigata, Japan

    T Furukawa & M Masuko

  3. Nagaoka Red Cross Hospital, Nagaoka, Japan

    N Sato

  4. Division of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata, Japan

    M Takahashi

Authors
  1. N Izumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Furukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Okazuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Tsukada
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Yano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T Kurasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M Masuko
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K Toba
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Y Aizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T Furukawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Izumi, N., Furukawa, T., Sato, N. et al. Risk factors for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: retrospective analysis of 73 patients who received cyclosporin A. Bone Marrow Transplant 40, 875–880 (2007). https://doi.org/10.1038/sj.bmt.1705834

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705834

Keywords

This article is cited by

Search

Advanced search

Quick links