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:

Unrelated Donor Transplants

The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia

Bone Marrow Transplantation volume 25, pages 411–417 (2000)Cite this article

Abstract

unrelated donor (ud) transplantation is the only potentially curative therapy for many leukaemia patients but is associated with a high mortality and morbidity. we sought to identify factors that could be optimised to improve outcome following ud transplantation in adults. data was retrospectively analysed on 55 patients sequentially receiving ud transplants for cml or acute leukaemia (al), all of whom received serotherapy for the prevention of gvhd and rejection. all patients received standard conditioning regimens. the first 28 patients transplanted also received combined pre- and post-transplant serotherapy with campath 1g (days −5 to +5) and standard dose csa plus mtx as gvhd prophylaxis (protocol 1). the subsequent 27 patients received a 5-day course of pre-transplant serotherapy alone either with atg (cml patients) or campath 1g (al patients) on days −5 to −1 inclusive, with high-dose csa plus mtx (protocol 2). the incidence of acute gvhd was low with no patient receiving either protocol developing >grade 2 disease. The use of protocol 2 and the administration of a bone marrow cell dose above the median (2.17 × 108/kg) were the most important factors predicting engraftment (P = 0.03 and P = 0.001, respectively) but this only remained significant for cell dose in multivariate analysis (P = 0.03). Overall survival for the group was 45% at 3 years and was influenced by both age (P = 0.02) and disease status at transplantation (P = 0.001). Receiving a cell dose above the median was also associated with a trend towards better survival (P = 0.08), due primarily to a reduction in the TRM to 8.2% compared with 54.5% in those receiving a lower cell dose (P = 0.002). We conclude that pre-transplant serotherapy alone is highly effective at preventing acute GVHD following UD BMT and that additional post-transplant serotherapy does not confer any benefit. Furthermore, a high marrow cell dose infused has a major effect in reducing transplant-related mortality following UD BMT. Bone Marrow Transplantation (2000) 25, 411–417.

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. Thomas E . Marrow transplantation for malignant diseases J Clin Oncol 1983 1: 517–521

    Article  CAS  PubMed  Google Scholar 

  2. Thomas E, Clift R, Fefer A et al. Marrow transplantation for the treatment of chronic myelogenous leukemia Ann Intern Med 1986 104: 155–163

    Article  CAS  PubMed  Google Scholar 

  3. Goldman J, Apperley J, Jones L et al. Bone marrow transplantation for patients with chronic myeloid leukemia New Engl J Med 1986 314: 202–207

    Article  CAS  PubMed  Google Scholar 

  4. Beatty P, Dahlberg S, Milford E . Impact of racial genetic polymorphism on the probability of finding an HLA-matched donor Transplantation 1995 52: 778–782

    Article  Google Scholar 

  5. Goldman J for the WMDA Executive Committee . A special report: bone marrow transplants using volunteer donors – recommendations and requirements for a standardised practice throughout the world – 1994 update Blood 1994 84: 2833–2839

    Google Scholar 

  6. Beatty P, Ash R, Hows J, McGlave P . The use of unrelated bone marrow donors in the treatment of patients with chronic myelogenous leukemia: experience of four marrow transplant centres Bone Marrow Transplant 1985 4: 287–290

    Google Scholar 

  7. McGlave P, Beatty P, Ash R, Hows J . Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases Blood 1990 75: 1728–1732

    CAS  PubMed  Google Scholar 

  8. Mackinnon S, Barnett L, Heller G, Or J . Minimal residual disease is more common in patients who have mixed T-cell chimerism after bone marrow transplantation for chronic myelogenous leukaemia Blood 1994 83: 3409–3416

    CAS  PubMed  Google Scholar 

  9. McGlave P, Barrsch G, Anasetti C et al. Unrelated donor transplantation therapy for chronic myeloid leukemia: initial experience of the National Bone Marrow Donor Program Blood 1993 81: 543–550

    CAS  PubMed  Google Scholar 

  10. Marks D, Cullis J, Ward K et al. Allogeneic bone marrow transplantation for chronic myeloid leukemia using sibling and volunteer unrelated donors: a comparison of complications in the first 2 years Ann Intern Med 1993 19: 207–214

    Article  Google Scholar 

  11. Hansen J, Gooley T, Martin P et al. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia New Engl J Med 1998 338: 962–968

    Article  CAS  PubMed  Google Scholar 

  12. Anasetti C, Hansen J . Effect of HLA incompatibility in marrow transplantation from unrelated and HLA-mismatched related donors Transfus Sci 1994 15: 221–230

    Article  CAS  PubMed  Google Scholar 

  13. Davies S, Shu X, Blazar B et al. Unrelated donor bone marrow transplantation: influence of HLA-A and B incompatibility on outcome Blood 1995 86: 1636–1642

    CAS  PubMed  Google Scholar 

  14. Petersdorf E, Longton G, Anasetti C et al. The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR identical unrelated donor marrow transplantation Blood 1995 86: 1606–1613

    CAS  PubMed  Google Scholar 

  15. Sazasuki T, Takeo J, Morishima Y et al. Effect of matching class I alleles on clinical outcome after transplantation of hematopoietic cells from an unrelated donor New Engl J Med 1998 339: 1177–1185

    Article  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  17. Forman SJ, Zaia JA . Treatment and prevention of cytomegalovirus pneumonia after bone marrow transplantation: where do we stand? Blood 1994 83: 2392–2398

    CAS  PubMed  Google Scholar 

  18. Takenaka K, Gondo H, Yanimoto K et al. Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors Bone Marrow Transplant 1997 19: 241–248

    Article  CAS  PubMed  Google Scholar 

  19. Goodrich J, Bowden R, Fisher L et al. Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic bone marrow transplant Ann Intern Med 1993 84: 1067–1071

    Google Scholar 

  20. Goodrich J, Mori M, Gleaves C et al. Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation New Engl J Med 1991 325: 1601–1607

    Article  CAS  PubMed  Google Scholar 

  21. Ringden O, Remberger M, Persson U et al. Similar incidence of graft-versus-host disease using HLA-A, B and DR identical unrelated bone marrow donors as with HLA-identical siblings Bone Marrow Transplant 1995 15: 619–625

    CAS  PubMed  Google Scholar 

  22. Glucksberg H, Storb R, Fefer A . Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors Transplant 1974 18: 295–304

    Article  CAS  Google Scholar 

  23. Schulman K, Sullivan KM, Weiden P . Chronic graft-versus-host disease in man: a long-term clinicopathologic study of 20 Seattle patients Am J Med 1980 69: 204–217

    Article  Google Scholar 

  24. Sierra J, Storer B, Hansen J et al. Transplantation of marrow cells from unrelated donors for treatment of high risk acute leukaemia: the effect of leukaemic burden, donor HLA-matching and marrow cell dose Blood 1997 89: 4226–4235

    CAS  PubMed  Google Scholar 

  25. Clift R, Buckner C, Thomas E et al. The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation Bone Marrow Transplant 1987 243: 243–248

    Google Scholar 

  26. Bortin M, Gale R, Kay H, Rimm A . Bone marrow transplantation for acute myelogenous leukaemia. Factors associated with early mortality JAMA 1983 249: 1166–1170

    Article  CAS  PubMed  Google Scholar 

  27. Kernan NA, Bartsch G, Ash RC et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program New Engl J Med 1993 328: 593–602

    Article  CAS  PubMed  Google Scholar 

  28. Hale G, Bright S, Chumbley G et al. Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes complement Blood 1983 62: 873–882

    CAS  PubMed  Google Scholar 

  29. Reisner Y, Kapoor N, Kirkpatrick D et al. Transplantation for acute leukaemia with HLA-A and B non-identical parental marrow cells fractionated with soybean agglutin and sheep red blood cells Lancet 1981 2: 327–330

    Article  CAS  PubMed  Google Scholar 

  30. Prentice HG, Blacklock H, Janossy G et al. Use of anti-T cell monoclonal antibody OKT3v to prevent acute graft-versus-host disease in allogeneic bone marrow transplantation for acute leukaemia Lancet 1982 1: 700–703

    Article  CAS  PubMed  Google Scholar 

  31. Prentice H, Janossy G, Price-Jones L et al. Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukaemic marrow recipients Lancet 1984 1: 472–476

    Article  CAS  PubMed  Google Scholar 

  32. Waldmann H, Or R, Hale G et al. Elimination of graft-versus-host disease by in vitro depletion of alloreactive lymphocytes using a monoclonal rat anti-human lymphocyte antibody (CAMPATH 1) Lancet 1984 2: 483–485

    Article  CAS  PubMed  Google Scholar 

  33. Filipovich A, Vallera D, Youle R et al. Graft-versus-host disease prevention in allogeneic bone marrow transplantation from histocompatible siblings. A pilot study using immunotoxins for T cell depletion of lymphocytes from human bone marrow Transplantation 1987 44: 62–69

    Article  CAS  PubMed  Google Scholar 

  34. Kernan N, Flomenberg N, Dupont B, O'Reilly R . Graft rejection in recipients of T-cell depleted HLA-identical marrow transplants for leukaemia. Identification of host-derived anti-donor allocytotoxic T lymphocytes Transplantation 1987 43: 842–846

    Article  CAS  PubMed  Google Scholar 

  35. Bunjes D, Heit W, Arnold R et al. Evidence for the involvement of host-derived OKT8 positive T cells in the rejection of T-depleted HLA-identical bone marrow grafts Transplantation 1987 43: 501–505

    Article  CAS  PubMed  Google Scholar 

  36. Apperley J, Mauro F, Goldman J et al. Bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: importance of a graft-versus-leukaemia effect BrJ Haematol 1988 9: 239–234

    Article  Google Scholar 

  37. Hale G, Cobbold S, Waldmann H . T-cell depletion with CAMPATH-1 in allogeneic bone marrow transplantation Transplantation 1988 45: 753–757

    Article  CAS  PubMed  Google Scholar 

  38. Slavin S, Or R, Naparstek E et al. New approaches for the prevention of graft-versus-host disease in clinical bone marrow transplantation Isr J Med Sci 1986 22: 264–267

    CAS  PubMed  Google Scholar 

  39. Patterson J, Prentice H, Brenner M et al. Graft rejection following HLA-matched T-lymphocyte depleted bone marrow transplantation Br J Haematol 1986 63: 221–225

    Article  CAS  PubMed  Google Scholar 

  40. Hale G, Zhang M-J, 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 

  41. Cull G, Haynes AP, Byrne JL et al. Allogeneic stem cell transplantation for lymphoproliferative disorders using BEAM-Campath conditioning Br J Haematol 2000 (in press)

  42. Baurmann H, Schimmelpfennig C, Brauninger S et al. ATG as part of the conditioning in matched unrelated (MUD) BMT Bone Marrow Transplant 1998 21: (Suppl. 1) 336a

    Google Scholar 

  43. Vitek A, Sajdova J, Hrabenek J et al. ATG reduces the risk of severe aGVHD in MUD or haploidentical BMT Bone Marrow Transplant 1998 21: (Suppl. 1) 406a

    Google Scholar 

  44. Stockschlader M, Kruger W, Betke R et al. ATG as part of the pre-transplant conditioning regimen reduces transplant-related mortality in CML patients undergoing allogeneic transplantation Exp Hematol 1996 24: 679a

    Google Scholar 

  45. Lanino E, Locatelli F, Porta C et al. Pre-transplant ATG vs Campath IG for GVHD prophylaxis in pediatric recipients of unrelated BMT. An AIEOP-GITMO retrospective analysis of 112 patients Bone Marrow Transplant 1998 21: (Suppl. 1) 411a

    Google Scholar 

  46. Kato S, Kodera Y, Nagao T et al. Effect of ATG in conditioning for unrelated BMT on GVHD prophylaxis. A preliminary report of prospective cooperative study in Japan Exp Haematol 1996 24: 655a

    Google Scholar 

  47. Holler E, Ledderose G, Knabe H et al. ATG serotherapy during pre-transplant conditioning in unrelated donor BMT: dose-dependent modulation of GVHD Bone Marrow Transplant 1998 21: (Suppl. 1) 105a

    Article  Google Scholar 

  48. Estey E, Plunkett W, Ghandi V et al. Fludarabine and arabinosylcytosine therapy of refractory and relapsed acute myelogenous leukemia Leuk Lymphoma 1993 9: 343–350

    Article  CAS  PubMed  Google Scholar 

  49. Hale G, Swirsky D, Waldmann H, Chan L . Reactivity of rat monoclonal antibody CAMPATH-1 with human leukaemia cells and its possible application for autologous bone marrow transplantation Br J Haematol 1985 60: 41–48

    Article  CAS  PubMed  Google Scholar 

  50. Russell NH, Warwick R, Goldman J . Peripheral blood stem cells from unrelated donors for allogeneic transplantation Transplantation 1999 67: 339–340

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology, Nottingham City Hospital, UK

    JL Byrne, C Stainer, G Cull, AP Haynes & NH Russell

  2. Division of Haematology, School of Clinical Laboratory Sciences, University of Nottingham, UK

    JL Byrne, AP Haynes & NH Russell

  3. Department of Radiotherapy, Nottingham City Hospital, UK

    EM Bessell

  4. Sir William Dunn School of Pathology, University of Oxford, Oxford, UK

    G Hale & H Waldmann

Authors
  1. JL Byrne
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Stainer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Cull
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. AP Haynes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. EM Bessell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Hale
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H Waldmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. NH Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Byrne, J., Stainer, C., Cull, G. et al. The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia. Bone Marrow Transplant 25, 411–417 (2000). https://doi.org/10.1038/sj.bmt.1702165

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702165

Keywords

This article is cited by

Search

Advanced search

Quick links