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

In vivo T cell depletion with pretransplant anti-thymocyte globulin reduces graft-versus-host disease without increasing relapse in good risk myeloid leukemia patients after stem cell transplantation from matched related donors

Abstract

One-hundred and two patients with good risk myeloid leukemia (CML first chronic phase or AML first CR) were transplanted from HLA-related donors after conditioning with (n = 45) or without anti-thymocyte globulin (ATG) (n = 57). One graft failure was observed in the non-ATG and none in the ATG group. The median time to leukocyte engraftment (>1 × 109/l) was 16 (range 12–33) in the ATG group and 17 days (range 11–29) in the non-ATG group (NS) and for platelet engraftment (>20 × 109/l) 24 and 19 days (P = 0.002), respectively. Acute GVHD grade II–IV was observed in 47% of the non-ATG and in 20% of the ATG group (P = 0.004). Grade III/IV GVHD occurred in 7% of the ATG and in 32% of the non-ATG group (P = 0.002). Chronic GVHD was seen in 36% and 67% (P = 0.005), respectively. After a median follow-up of 48 months (range 2–128), the 5-year estimated OS is 66% (95% KI: 51–81%) for the ATG group and 59% (95% KI: 46–72%) for the non-ATG group (NS). The 5-year estimated DFS is 64% (95% KI: 50–78%) for ATG and 55% (95% KI: 43–67%) for the non-ATG regimen (NS). The 5-year probability of relapse was 5% in the ATG and 15% in the non-ATG group (NS). ATG as part of the conditioning regimen leads to a significant reduction in GVHD without increase of relapse in patients with myeloid leukemia after stem cell transplantation from HLA-related donors.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Sullivan K, Weiden P, Storb R et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical sibling as treatment of acute and chronic leukemia Blood 1989 73: 170 178

    Google Scholar 

  2. Martin P, Hansen J, Torok-Storb B et al. Graft failure in patients receiving T cell depleted HLA-identical allogeneic marrow transplants Bone Marrow Transplant 1988 3: 445 456

    CAS  PubMed  Google Scholar 

  3. Apperley J, Jones L, Hale G et al. Bone marrow transplantation for patients with chronic myeloid leukaemia: T cell depletion with CAMPATH-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse Bone Marrow Transplant 1986 1: 53 66

    CAS  PubMed  Google Scholar 

  4. Champlin R, Ho W, Mitsuyasu R et al. Graft failure and leukaemia relapse following T lymphocyte-depleted bone marrow transplants: effect of intensification of immunosuppressive conditioning Transplant Proc 1987 19: 2616 2619

    CAS  PubMed  Google Scholar 

  5. Goldman J, Gale R, Horowitz M et al. Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk of relapse associated with T cell depletion Ann Intern Med 1988 108: 806 814

    Article  CAS  PubMed  Google Scholar 

  6. Marmont A, Horowitz M, Gale R et al. T cell depletion of HLA-identical transplants in leukemia Blood 1991 78: 2120 2130

    CAS  PubMed  Google Scholar 

  7. Champlin R, Winston H, Gajewski J et al. Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation Blood 1990 76: 418 423

    CAS  PubMed  Google Scholar 

  8. Verdonck L, Dekker A, De Gast G et al. Allogeneic bone marrow transplantation with a fixed low number of T cells in the marrow graft Blood 1994 83: 3090 3096

    CAS  PubMed  Google Scholar 

  9. Naparstek E, Or R, Nagler A et al. T cell-depleted allogeneic bone marrow transplantation for acute leukaemia using CAMPATH-1 antibodies and post transplant administration of donors peripheral blood lymphocytes for prevention of relapse Br J Haematol 1995 89: 506 515

    Article  CAS  PubMed  Google Scholar 

  10. Bunjes D, Hertenstein B, Wiesneth M et al. In vivo/ex vivo T cell depletion reduces the morbidity of allogeneic transplantation in patients with acute leukaemias in first remission without increasing the risk of treatment failure: comparison with cyclosporin/methotrexate Bone Marrow Transplant 1995 15: 563 568

    CAS  PubMed  Google Scholar 

  11. Heit W, Bunjes D, Wiesneth M et al. Ex vivo T cell depletion with the monoclonal antibody CAMPATH-1 plus human complement effectively prevents acute graft-versus-host disease in allogeneic bone marrow transplantation Br J Haematol 1986 64: 479 486

    Article  CAS  PubMed  Google Scholar 

  12. Hale G, Zhang MJ, Bunjes D et al. Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection Blood 1998 92: 4581 4590

    CAS  PubMed  Google Scholar 

  13. Kröger N, Zabelina T, Krüger W et al. Anti-thymocyte-globulin as part of the preparative regimen prevents acute and chronic graft-versus-host disease (GVHD) in allogeneic stem cell transplantation from unrelated donors Ann Hematol 2001 80: 209 215

    Article  PubMed  Google Scholar 

  14. Finke J, Bertz H, Schmoor C et al. Allogeneic bone marrow transplantation from unrelated donors using in vivo anti T cell globulin Br J Haematol 2000 11: 303 313

    Article  Google Scholar 

  15. Zander AR, Zabelina T, Kröger N et al. Use of a five-agent GVHD prevention regimen in recipients of unrelated donor marrow Bone Marrow Transplant 1999 23: 889 893

    Article  CAS  PubMed  Google Scholar 

  16. Aversa F, Terenzi A, Carotti A et al. Improved outcome with T cell-depleted bone marrow transplantation for acute leukemia J Clin Oncol 1999 17: 1545 1550

    Article  CAS  PubMed  Google Scholar 

  17. Papadopoulos EB, Carabasi MH, Castro-Malaspina H et al. T cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease Blood 1998 91: 1083 1090

    CAS  PubMed  Google Scholar 

  18. Przepiorka KM, Weisdorf D, Martin P . 1994 Consensus Conference on acute GVHD-grading Bone Marrow Transplant 1995 15: 825 828

    CAS  PubMed  Google Scholar 

  19. Bearman SI, Appelbaum FR, Buckner CD et al. Regimen related toxicity in patients undergoing bone marrow transplantation J Clin Oncol 1988 6: 1562 1568

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Storb R, Etzioni R, Anasetti C et al. Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia Blood 1994 84: 941 949

    CAS  PubMed  Google Scholar 

  22. Horstmann M, Stockschläder M, Krüger W et al. Cyclophosphamide/antithymocyte globulin conditioning of patients with severe aplastic anemia for marrow transplantation from HLA-matched siblings: preliminary results Ann Hematol 1995 71: 77 81

    Article  CAS  PubMed  Google Scholar 

  23. Baurmann H, Revillard JP, Bonnefoy-Berard N et al. Potent effect of ATG as part of the conditioning in matched unrelated donor (MUD) transplantation Blood 1998 92: (Suppl. 1) 290a

    Google Scholar 

  24. Kolb HJ, Holler E, Knabe H et al. Conditioning treatment with antithymocyte globulin (ATG) modifies graft-versus-host disease in recipients of marrow from unrelated donors Blood 1995 86:: (Suppl. 1) 952a

    Google Scholar 

  25. Young J, Papadopoulos E, Cunningham I et al. T cell depleted allogeneic bone marrow transplantation in adults with acute nonlymphocytic leukemia in first remission Blood 1992 79: 3380 3387

    CAS  PubMed  Google Scholar 

  26. Barrett A, Mavroudis D, Tisdale J et al. T cell depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft versus leukemia effect Bone Marrow Transplant 1998 21: 543 551

    Article  CAS  PubMed  Google Scholar 

  27. Eiermann TH, Lembrecht P, Zander AR . Monitoring anti-thymocyte globulin (ATG) in bone marrow recipients Bone Marrow Transplant 1999 23: 779 781

    Article  CAS  PubMed  Google Scholar 

  28. Remberger M, Svahn BM, Hentschke P et al. Effect on cytokine release, engraftment and GVHD of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation Bone Marrow Transplant 1999 23: (Suppl. 1) 268

    Google Scholar 

  29. Curtis R, Travis L, Rowlings P et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study Blood 1999 94: 2208 2216

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the staff of the BMT unit for providing excellent care of our patients and the medical technicians for their excellent work in the BMT laboratory.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kröger, N., Zabelina, T., Krüger, W. et al. In vivo T cell depletion with pretransplant anti-thymocyte globulin reduces graft-versus-host disease without increasing relapse in good risk myeloid leukemia patients after stem cell transplantation from matched related donors. Bone Marrow Transplant 29, 683–689 (2002). https://doi.org/10.1038/sj.bmt.1703530

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703530

Keywords

This article is cited by

Search

Quick links