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

Long-term follow-up of patients treated with daclizumab for steroid-refractory acute graft-vs-host disease

Abstract

Daclizumab has been shown to have activity in acute GVHD, but appears to be associated with an increased risk of infection. To investigate further the long-term effects of daclizumab, we performed a retrospective review of 57 patients who underwent an allogeneic hematopoietic stem cell transplant from January 1993 through June 2000 and were treated with daclizumab for steroid-refractory acute GVHD. The median number of daclizumab doses given was 5 (range 1–22). GVHD was assessed at baseline, days 15, 29 and 43. By day 43, 54% patients had an improvement in their overall GVHD score, including 76% patients aged 18. Opportunistic infections developed in 95% patients. Forty-three patients (75%) died following treatment with daclizumab. The causes of death included active GVHD and infection (79%), active GVHD (5%), chronic GVHD (2%) and relapse (14%). Patients with grade 3–4 GVHD had a significantly shorter median survival than patients with grade 1–2 GVHD (2.0 vs 5.1 months, P=0.001). Daclizumab has no infusion-related toxicity, is active in steroid-refractory GVHD, especially among pediatric patients, but is associated with significant morbidity and mortality due to infectious complications. Careful patient selection and aggressive prophylaxis against viral and fungal infections are recommended.

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

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Ferrara JL, Levy R, Chao NJ . Pathophysiologic mechanisms of acute graft-vs-host disease. Biol Blood Marrow Transplant 1999; 5: 347–356.

    Article  CAS  PubMed  Google Scholar 

  2. van den Brink MR, Burakoff SJ . Cytolytic pathways in haematopoietic stem-cell transplantation. Nat Rev Immunol 2002; 2: 273–281.

    Article  CAS  PubMed  Google Scholar 

  3. Waldmann TA . The structure, function, and expression of interleukin-2 receptors on normal and malignant lymphocytes. Science 1986; 232: 727–732.

    Article  CAS  PubMed  Google Scholar 

  4. Takeshita T, Asao H, Ohtani K, Ishii N, Kumaki S, Tanaka N et al. Cloning of the gamma chain of the human IL-2 receptor. Science 1992; 257: 379–382.

    Article  CAS  PubMed  Google Scholar 

  5. Uchiyama T, Broder S, Waldmann TA . A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. J Immunol 1981; 126: 1393–1397.

    CAS  PubMed  Google Scholar 

  6. Uchiyama T, Nelson DL, Fleisher TA, Waldmann TA . A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. II. Expression of Tac antigen on activated cytotoxic killer T cells, suppressor cells, and on one of two types of helper T cells. J Immunol 1981; 126: 1398–1403.

    CAS  PubMed  Google Scholar 

  7. Queen C, Schneider WP, Selick HE, Payne PW, Landolfi NF, Duncan JF et al. A humanized antibody that binds to the interleukin 2 receptor. Proc Natl Acad Sci USA 1989; 86: 10029–10033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Junghans RP, Waldmann TA, Landolfi NF, Avdalovic NM, Schneider WP, Queen C . Anti-Tac-H, a humanized antibody to the interleukin 2 receptor with new features for immunotherapy in malignant and immune disorders. Cancer Res 1990; 50: 1495–1502.

    CAS  PubMed  Google Scholar 

  9. Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, Halloran P et al. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N Engl J Med 1998; 338: 161–165.

    Article  CAS  PubMed  Google Scholar 

  10. Anasetti C, Hansen JA, Waldmann TA, Appelbaum FR, Davis J, Deeg HJ et al. Treatment of acute graft-versus-host disease with humanized anti-Tac: an antibody that binds to the interleukin-2 receptor. Blood 1994; 84: 1320–1327.

    CAS  PubMed  Google Scholar 

  11. Przepiorka D, Kernan NA, Ippoliti C, Papadopoulos EB, Giralt S, Khouri I et al. Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood 2000; 95: 83–89.

    CAS  PubMed  Google Scholar 

  12. Willenbacher W, Basara N, Blau IW, Fauser AA, Kiehl MG . Treatment of steroid refractory acute and chronic graft-versus-host disease with daclizumab. Br J Haematol 2001; 112: 820–823.

    Article  CAS  PubMed  Google Scholar 

  13. Srinivasan R, Chakrabarti S, Walsh T, Igarashi T, Takahashi Y, Kleiner D et al. Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis. Br J Haematol 2004; 124: 777–786.

    Article  CAS  PubMed  Google Scholar 

  14. Teachey DT, Bickert B, Bunin N . Daclizumab for children with corticosteroid refractory graft-versus-host disease. Bone Marrow Transplant 2006; 37: 95–99.

    Article  CAS  PubMed  Google Scholar 

  15. Wagner JE, Thompson JS, Carter SL, Kernan NA . Effect of graft-versus-host disease prophylaxis on 3-year disease-free survival in recipients of unrelated donor bone marrow (T-cell Depletion Trial): a multi-centre, randomised phase II-III trial. Lancet 2005; 366: 733–741.

    Article  CAS  PubMed  Google Scholar 

  16. 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 

  17. Arai S, Margolis J, Zahurak M, Anders V, Vogelsang GB . Poor outcome in steroid-refractory graft-versus-host disease with antithymocyte globulin treatment. Biol Blood Marrow Transplant 2002; 8: 155–160.

    Article  PubMed  Google Scholar 

  18. McCaul KG, Nevill TJ, Barnett MJ, Toze CL, Currie CJ, Sutherland HJ et al. Treatment of steroid-resistant acute graft-versus-host disease with rabbit antithymocyte globulin. J Hematother Stem Cell Res 2000; 9: 367–374.

    Article  CAS  PubMed  Google Scholar 

  19. Remberger M, Ringden O, Aschan J, Ljungman P, Lonnqvist B, Markling L . Long-term follow-up of a randomized trial comparing T-cell depletion with a combination of methotrexate and cyclosporine in adult leukemic marrow transplant recipients. Transplant Proc 1994; 26: 1829–1830.

    CAS  PubMed  Google Scholar 

  20. Khoury H, Kashyap A, Adkins DR, Brown RA, Miller G, Vij R et al. Treatment of steroid-resistant acute graft-versus-host disease with anti-thymocyte globulin. Bone Marrow Transplant 2001; 27: 1059–1064.

    Article  CAS  PubMed  Google Scholar 

  21. Webster AC, Playford EG, Higgins G, Chapman JR, Craig JC . Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials. Transplantation 2004; 77: 166–176.

    Article  CAS  PubMed  Google Scholar 

  22. Blaise D, Olive D, Michallet M, Marit G, Leblond V, Maraninchi D . Impairment of leukaemia-free survival by addition of interleukin-2-receptor antibody to standard graft-versus-host prophylaxis. Lancet 1995; 345: 1144–1146.

    Article  CAS  PubMed  Google Scholar 

  23. Belanger C, Esperou-Bourdeau H, Bordigoni P, Jouet JP, Souillet G, Milpied N et al. Use of an anti-interleukin-2 receptor monoclonal antibody for GVHD prophylaxis in unrelated donor BMT. Bone Marrow Transplant 1993; 11: 293–297.

    CAS  PubMed  Google Scholar 

  24. Lee SJ, Zahrieh D, Agura E, MacMillan ML, Maziarz RT, McCarthy Jr PL et al. Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial. Blood 2004; 104: 1559–1564.

    Article  CAS  PubMed  Google Scholar 

  25. Cragg L, Blazar BR, Defor T, Kolatker N, Miller W, Kersey J et al. A randomized trial comparing prednisone with antithymocyte globulin/prednisone as an initial systemic therapy for moderately severe acute graft-versus-host disease. Biol Blood Marrow Transplant 2000; 6: 441–447.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Supported in part by P01 CA23766. Additional support by the Charles A Dana Fellowship (MAP, DMW), the Clinical Scholars Biomedical Research Training Program (MAP, DMW), NIH CA09512 (MAP, DMW) and NIH CA09207, CA10260 (MAP) and the Leukemia and Lymphoma Society 5415-05 (DMW).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M-A Perales.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perales, MA., Ishill, N., Lomazow, W. et al. Long-term follow-up of patients treated with daclizumab for steroid-refractory acute graft-vs-host disease. Bone Marrow Transplant 40, 481–486 (2007). https://doi.org/10.1038/sj.bmt.1705762

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705762

Keywords

This article is cited by

Search

Quick links