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

Anti-CD25 monoclonal antibody (basiliximab) for prevention of graft-versus-host disease after haploidentical bone marrow transplantation for hematological malignancies

Bone Marrow Transplantation volume 36, pages 349–354 (2005)Cite this article

Summary:

Haploidentical donors are available for most patients who need allografts but do not have matched donors. However, GVHD, rejection, delayed immune reconstitution, and infections have been significant barriers. We designed a haploidentical BMT protocol focusing on prevention of GVHD and rejection. A total of 53 leukemic patients underwent haploidentical G-CSF-primed BMT without ex vivo T-cell depletion. GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine, methotrexate, and mycophenolate mofetil. In all, 38 patients (the CD25 group) received additional anti-CD25 monoclonal antibody basiliximab. The results were compared to 15 patients who did not receive basiliximab. All patients achieved trilineage engraftment with full-donor chimerism. The incidence of acute II–IV GVHD was 11% in the CD25 group vs 33% in the control group (P=0.046). The overall incidence of extensive chronic GVHD was 15%. T, B, and NK cells recovered within 12 months post transplant. The disease-free survival at 2 years was 53% with a median follow-up of 31 months. In conclusion, G-CSF primed haploidentical BMT along with sequential immunosuppressive agents as described here deserves further study.

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

Similar content being viewed by others

References

  1. Henslee-Downey PJ . Choosing an alternative bone marrow donor among available family members. Am J Pediatr Hematol Oncol 1993; 15: 150–161.

    Article  CAS  PubMed  Google Scholar 

  2. Beatty PG, Clift RA, Mickelson EM et al. Marrow transplantation from related donors other than HLA-identical siblings. New Engl J Med 1985; 313: 765–771.

    Article  CAS  PubMed  Google Scholar 

  3. Anasetti C, Amos D, Beatty PG et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. New Engl J Med 1989; 320: 197–204.

    Article  CAS  PubMed  Google Scholar 

  4. Deeg HJ, Spitzer TR, Cottler-Fax M et al. Conditioning-related toxicity and acute GVHD in patients given methotrexate/cyclosporine prophylaxis. Bone Marrow Transplant 1991; 7: 193–198.

    CAS  PubMed  Google Scholar 

  5. Xun CQ, Thompson JS, Jennings CD et al. Effect of total body irradiation, busulfan-cyclophosphamide or cyclophosphamide conditioning on inflammatory cytokine release in H-2 incompatible transplanted SCID mice. Blood 1994; 83: 2360–2367.

    CAS  PubMed  Google Scholar 

  6. Ash RC, Horowitz MM, Gale RP et al. Bone Marrow Transplantation from related donors other than HLA-identical siblings of T cell depletion. Bone Marrow Transplant 1991; 7: 443–452.

    CAS  PubMed  Google Scholar 

  7. Bozdech MJ, Sondel PM, Trigg ME et al. Transplantation of HLA-haploidentical T cell depleted marrow for leukemia addition of cytosine arabinoside to the pretransplant conditioning prevents rejection. Exp Hematol 1985; 13: 1201–1210.

    CAS  PubMed  Google Scholar 

  8. Aversa F, Tabilio A, Velardi A et al. Treatment of high-risk acute leukemia with T cell-depleted stem cells from related donor with one full mismatched HLA haplotype. New Engl J Med 1998; 339: 1186–1193.

    Article  CAS  PubMed  Google Scholar 

  9. Serody JS, Sparks SD, Lin Y et al. Comparison of G-CSF-mobilized peripheral blood progenitor cells and G-CSF-stimulated bone marrow as a source of stem cells in HLA-matched sibling transplantation. Biol Blood Marrow Transplant 2000; 6: 434–440.

    Article  CAS  PubMed  Google Scholar 

  10. Ji SQ, Chen HR, Xun CQ et al. The effect of G-CSF-stimulated donor marrow on engraftment and incidence of graft-versus-host disease in allogeneic bone marrow transplantation. Clin Transplant 2001; 15: 317–323.

    Article  CAS  PubMed  Google Scholar 

  11. Ji SQ, Chen HR, Wang HX et al. Comparison outcome of allogeneic bone marrow transplantation with and without granulocyte colony stimulating factor (G-CSF) (lenograstim) donor marrow priming in patients with chronic myelogenous leukemia (CML). Biol Blood Marrow Transplant. 2002; 8: 261–267.

    Article  PubMed  Google Scholar 

  12. Ji SQ, Chen HR, Wang HX et al. G-CSF primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia. Bone Marrow Transplant 2002; 30: 861–866.

    Article  PubMed  Google Scholar 

  13. Kovarik JM, Rawlings E, Sweny P et al. Prolonged action of a chimeric interleukin-2 receptor (CD25) monoclonal antibody used in cadaveric renal transplantation. Transplantation 1995; 60: 748–756.

    Article  Google Scholar 

  14. Przepiorka D, Weisdorf D, Martin P et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  15. Vij R, Khoury H, Brown R et al. Low-dose short-course intravenous Ganciclovir as pre-emptive therapy for CMV viremia post allo-PBSC transplantation. Bone Marrow Transplant 2003; 32: 703–707.

    Article  CAS  PubMed  Google Scholar 

  16. Verma A, Devine S, Morrow M et al. Low incidence of CMV viremia and disease after allogeneic peripheral blood stem cell transplantation. Role of pretransplant Ganciclovir and post-transplant acyclovir. Bone Marrow Transplant 2003; 31: 813–817.

    Article  CAS  PubMed  Google Scholar 

  17. Hows J, Bradley BA, Gore S et al. Prospective evaluation of unrelated donor bone marrow transplantation. Bone Marrow Transplant 1993; 12: 371–380.

    CAS  PubMed  Google Scholar 

  18. Nademance A, Schmiat GH, Parker P 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 prophylaxis regimen of cyclosporine, methotrexate, and prednisone. Blood 1995; 86: 1228–1234.

    Google Scholar 

  19. Balduzzi A, Gooley T, Anasetti C et al. Unrelated donor marrow transplantation in children. Blood 1995; 86: 3247–3256.

    CAS  PubMed  Google Scholar 

  20. Ringen O, Horowtitz MM, Sondel P et al. Methotrexate, cyclosporin, or both to prevent graft-versus-host disease after HLA-identical sibling bone marrow transplants for early leukemia? Blood 1993; 81: 1094–1101.

    Google Scholar 

  21. Bensinger WI, Weaver CH, Appelbaum FR et al. Transplantation of allogeneic peripheral blood stem cell mobilized by recombinant human granulocyte colony-stimulating factor. Blood 1995; 85: 1655–1658.

    CAS  PubMed  Google Scholar 

  22. Donato M, Champlin R . GCSF primed allogeneic bone marrow transplants: capturing the advantage of blood stem cell transplants without increased risk of chronic GVHD. Biol Blood Marrow Transplant 2000; 6: 419–421.

    Article  CAS  PubMed  Google Scholar 

  23. Salgame P, Abrams JS, Clayberger C et al. Differing lymphokine profiles of function subset of human CD4 and CD8T cell clones. Science 1991; 254: 279–282.

    Article  CAS  PubMed  Google Scholar 

  24. Ferrara JL . Pathogenesis of acute graft-versus-host disease: cytokines and cellular effectors. J Hematother Stem Cell Res 2000; 9: 299–306.

    Article  CAS  PubMed  Google Scholar 

  25. Krenger W, Cooke KR, Crawford JM et al. Transplantation of polarized type 2 donor T cell reduces mortality caused by experimental graft-versus-host disease. Transplantation 1996; 62: 1278–1285.

    Article  CAS  PubMed  Google Scholar 

  26. Pan L, Delmonte Jr J, Jalonen CK et al. Pretreatment of donor mice with granulocyte colony-stimulating factor polarized donor T lymphocytes toward type 2 cytokine production and reduces severity of experimental graft-versus-host disease. Blood 1995; 86: 4422–4429.

    CAS  PubMed  Google Scholar 

  27. Tayebi H, Kuttler F, Saas P et al. Effect of granulocyte colony-stimulating factor mobilization on phenotypical and functional properties of immune cells. Exp Hematol 2001; 29: 458–470.

    Article  CAS  PubMed  Google Scholar 

  28. Starzling TE, Anthony JD, Noriko M . The two way paradigm. Immunol Today 1991; 12: 177–189.

    Article  Google Scholar 

  29. Strob R, Cong Y, Wanger JL et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal TBI before and pharmacological immunosuppression after marrow transplantation. Blood 1997; 89: 3048–3054.

    Google Scholar 

  30. Cavazzana-Calvo M, Fromont C, Le Deist F et al. Specific elimination of alloreactive T cells by an anti-interleukin-2 receptor B chain-specific immunotoxin. Transplantation 1990; 50: 1.

    Article  CAS  PubMed  Google Scholar 

  31. Cavazzana-Calvo M, Stephan JL, Sarnacki S et al. Attenuation of graft-versus-host disease and graft rejection by ex vivo immunotoxin elimination of alloreactive T cells in an H-2 haplotype disparate mouse combination. Blood 1994; 83: 288.

    CAS  PubMed  Google Scholar 

  32. Amlot PL, Rawlings E, Fernando ON et al. Prolonged action of a chimeric interleukin-2 receptor (CD25) monoclonal antibody used in cadaveric renal transplantation. Transplantation 1995; 60: 748.

    Article  CAS  PubMed  Google Scholar 

  33. Martin PJ, Pei J, Gooley T et al. Evaluation of a CD25-specific immunotoxin for prevention of graft-versus-host disease after unrelated marrow transplantation. Biol Blood Marrow Transplant 2004; 10: 552–560.

    Article  CAS  PubMed  Google Scholar 

  34. Kovaric JM, Rawlings E, Sweny P et al. Prolonged immunosuppressive effect and minimal immunogenicity from chimeric (CD25) monoclonal antibody SDZ CHI 621 in renal transplantation. Transplant Proc 1996; 28: 913.

    Google Scholar 

  35. Chen HR, Ji SQ, Wang HX et al. Humanized Anti-CD25 monoclonal antibody for prophylaxis of graft versus host disease (GVHD) in haploidentical bone marrow transplantation without ex-vivo T cell depletion. Exp Hematol 2003; 31: 1019–1025.

    Article  CAS  PubMed  Google Scholar 

  36. Sullivan KM, Weiden PL, Storb R et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA identical siblings as treatment of acute and chronic leukemia. Blood 1989; 73: 1720–1728.

    CAS  PubMed  Google Scholar 

  37. Horowitz MM, Gale RP, Sondel PM et al. Graft versus leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  38. Schiller G, Feig SA, Territo M et al. Treatment of advanced acute leukemia with allogeneic bone marrow transplantation from unrelated donors. Br J Haematol 1994; 88: 72–78.

    Article  CAS  PubMed  Google Scholar 

  39. Kook H, Goldman F, Padley D et al. Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children immunophenotypic analysis and factors affecting the speed of recovery. Blood 1996; 88: 1089–1097.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Institution of Hematology, and Air Force General Hospital, Air Force of China, PLA, Beijing, P.R. China

    S-Q Ji, H-R Chen, H-M Yan, H-X Wang, J Liu, P-y Zhu & M-h Xiao

  2. Department of Medicine, Division of Hematology/Oncology and Blood/Marrow Transplant Program, University of Kentucky and VA Medical Centers, Lexington, KY, USA

    C-Q Xun

Authors
  1. S-Q Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H-R Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H-M Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H-X Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P-y Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M-h Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C-Q Xun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C-Q Xun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ji, SQ., Chen, HR., Yan, HM. et al. Anti-CD25 monoclonal antibody (basiliximab) for prevention of graft-versus-host disease after haploidentical bone marrow transplantation for hematological malignancies. Bone Marrow Transplant 36, 349–354 (2005). https://doi.org/10.1038/sj.bmt.1705046

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705046

Keywords

This article is cited by

Search

Advanced search

Quick links