Abstract
Basiliximab is a chimeric monoclonal antibody that binds to the α chain of IL-2R on activated cytotoxic T-cells, inhibiting lymphocyte proliferation. We report 34 patients with refractory acute GVHD (grade III–IV) who received basiliximab from December 1998 to October 2003. Adults received 40 mg weekly (2–3 doses) and children received half of this dose. Median age was 13 years. Twenty-five donors were unrelated. The stem cell source was bone marrow in 30 and cord blood in four. Complete responses were seen in 27/32 patients (84%) with skin, 12/25 (48%) with gut and 6/23 (26%) with liver GVHD. Median duration of response was 38 days (5–1103). Overall survival at 5 years was 20%. Eleven patients (32%) are alive. The main causes of death were CMV (n=4), fungus (n=6), sepsis (n=8), hemorrhage (n=2), and relapse (n=2). Graft-versus-host disease flares were observed in 14 patients (41%), half being rescued by other therapies. In conclusion, basiliximab was able to induce complete responses in patients with refractory acute GVHD. Prospective studies are necessary to evaluate the optimal treatment schedule.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W et al. Methotrexate and cyclosporin compared with cyclosporin alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 1986; 314: 729–735.
Khoury H, Kashyap A, Adkins DR, Brown RA, Miller G, Vij R et al. Treatment of steroid resistent acute graft-versus-host disease with anti-thymocyte globulin. Bone marrow transplant 2001; 27: 1059–1064.
Klingebiel T, Schlegel PG . GVHD: overview on pathophysiology, incidence, clinical and biological features. Bone Marrow Transplant 1988; 21 (Suppl): 45–49.
Nademance A, Schmidt GM, Parker P, Dagis AC, Stein A, Snyder DS et al. The outcome of matched unrelated donor bone marrow transplantation in patients with hematologic malignancies using molecular typing for donor selection and graft-versus-host disease phophylaxis regimen of cyclosporine, methotrexate and prednisone. Blood 1995; 86: 1228–1234.
Willenbacher W, Basara N, Blau IW, Fauser AA, Kiehl MG . Treatment of steroid refractory graft versus host disease with daclizumab. Br J Haemtol 2001; 112: 820–823.
Aschan J . Treatment of moderate to severe acute graft-versus-host disease: a retrospective analysis. Bone Marrow Transplant 1994; 14: 601–607.
Weisdorf D, Haake R, Blazar B, Miller W, McGlave P, Ramsay N et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood 1990; 75: 1024–1030.
Martin PJ, Schoch G, Fisher L, Byers V, Appelbaum FR, McDonald GB et al. A retrospective alaysis of therapy for acute graft-versus-host disease: secondary treatment. Blood 1991; 77: 1821–1828.
Ferrara JLM, Deeg HJ . Graft-versus-host disease. N Engl J Med 1991; 324: 667–674.
Przepiorka D, Keman 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.
Ferrara JLM, Levy R, Chao N . Pathophysiologic mechanisms of acute graft-versus-host disease. Biol Blood Marrow Transplant 1999; 5: 347–356.
Ferrara J . The cytokine modulation of acute graft-versus-host disease. Bone Marrow Transplant 1988; 21 (Suppl 3): 13–15.
Chao NJ . Graft-versus-host disease: the viewpoint from donor T cell. Biol Blood Marrow Transplant 1997; 3: 1–10.
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.
Lee S, Zahrieh D, Agura E, MacMillan ML, Maziarz RT, McCarthy PL et al. Effect of upfront daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial. Blood 2004; 104: 1559–1563.
Cicceri F, Bernardi M, Peccatori J . Basiliximab (SimulectR) for the treatment of steroid-resistent graft versus host disease (GVHD) after nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT). Blood 2002; 100: 441 (abstract 5337).
Onrust SV, Wiseman LR . Basiliximab. Drugs 1999; 57: 207–213.
Pasquini R, Moreira VA, de Medeiros CR, Bonfim C . Basiliximab (bamab) – a selective interleukin-2 receptor antagonist – as therapy for refractory acute graft versus host disease (a-GVHD) following bone marrow transplantation (BMT). Blood 2000; 96: 177 (abstract 762).
Carpenter PA, Appelbaum FR, Corey L, Deeg HJ, Doney K, Gooley T et al. A humanized non-FcR-binding anti-CD3 antibody, visilizumab for treatment of steroid-refractory acute graft-versus-host disease. Blood 2002; 99: 2712–2719.
Couriel DR, Hicks K, Giralt S, Champlin RE . Role of tumor necrosis factor-alpha inhibition with infliximab in cancer therapy and hematopoietic stem cell transplantation. Curr Opin Oncol 2000; 12: 582–587.
Ho VT, Zahrieh D, Hochberg E, Micale E, Levin J, Reynolds C et al. Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood 2004; 104: 1224–1226.
Couriel D, Saliba R, Hicks K, Ippoliti C, de Lima M, Hosing C et al. Tumor necrosis fator-α blockade for the treatment of acute GVHD. Blood 2004; 104: 649–653.
Edinger M, Hoffman P, Emmann J, Drago K, Fathman CG, Strober S et al. CD4+CD25+ regulatory T-cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med 2003; 9: 1144–1150.
Hanash AM, Levy RB . Donor CD4+CD25+ T cells promote engraftment and tolerance following MHC-mismatched hematopoietic cell transplantation. Blood 2005; 105: 1828–1836.
Lesnikova M, Nikitine A, Gass J, Nash RA, Georges GE . In vitro depletion of CD4+CD25+ T regulatory (Treg) cells with denileukin diftitox (DAB389IL-2) increases T cell alloreactivity. Blood 2004; 104: 585 (abstract 2126).
Massenkeil G, Rackwitz S, Genvresse I, Rosen O, Dörken B, Arnold R et al. Basiliximab is well tolerated and effective in the treatment of steroid refractory acute graft-versus-host disease after allogeneic stem cell transplantation. Bone marrow transplant 2002; 30: 899–903.
Acknowledgements
We acknowledge Euza Ortega Toyonaga (RN); Heliz Regina Neves (statistician); Mary Evelyn Flowers, MD (FHCRC); Paul Andrew Carpenter, MD (FHCRC); and Carina Moravec, ARNP (FHCRC).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Funke, V., de Medeiros, C., Setúbal, D. et al. Therapy for severe refractory acute graft-versus-host disease with basiliximab, a selective interleukin-2 receptor antagonist. Bone Marrow Transplant 37, 961–965 (2006). https://doi.org/10.1038/sj.bmt.1705306
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1705306
Keywords
This article is cited by
-
Mesenchymal stromal cells plus basiliximab improve the response of steroid-refractory acute graft-versus-host disease as a second-line therapy: a multicentre, randomized, controlled trial
BMC Medicine (2024)
-
Ruxolitinib is an effective salvage treatment for multidrug-resistant graft-versus-host disease after haploidentical allogeneic hematopoietic stem cell transplantation without posttransplant cyclophosphamide
Annals of Hematology (2021)
-
Treatment and unmet needs in steroid-refractory acute graft-versus-host disease
Leukemia (2020)
-
The use of basiliximab–infliximab combination for the treatment of severe gastrointestinal acute GvHD
Bone Marrow Transplantation (2016)
-
Preemptive administration of human αβ T cell receptor-targeting monoclonal antibody GZ-αβTCR potently abrogates aggressive graft-versus-host disease in vivo
Annals of Hematology (2015)