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Graft Versus Host Disease

CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells

Bone Marrow Transplantation volume 26, pages 69–76 (2000)Cite this article

Abstract

Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic bone marrow transplantation, but can be avoided by removing T lymphocytes from the donor bone marrow. However, T cell depletion increases the risk of graft rejection. In this study, two strategies are used to overcome rejection: (1) use of high doses of stem cells obtained from peripheral blood (PBSC), (2) admixture with a CD52 monoclonal antibody in order to deplete both donor and residual recipient lymphocytes. Two antibodies are compared: CAMPATH-1G (rat IgG2b) and its humanized equivalent CAMPATH-1H (human IgG1). A total of 187 consecutive patients at six centers received PBSC transplants from HLA-matched siblings between 1997 and 1999. A wide spectrum of diseases, both malignant and non-malignant, was included. The recovery of CD34+ cells after antibody treatment was close to 100%. The risk of acute GVHD (grade 2 to 4) was 11% in the CAMPATH-1G group and 4% in the CAMPATH-1H group (P = NS). The risk of chronic GVHD (any grade) was 11% in the CAMPATH-1G group and 24% in the CAMPATH-1H group (P = 0.03) but the risk of extensive chronic GVHD was only 2%. The overall risk of graft failure/rejection was 2%, not significantly different between the two antibodies. Antibody treatment was equally effective at concentrations between 10 μg/ml and 120 μg/ml and it made no significant difference to the outcome whether the patients received post-transplant immunosuppression or not (87% did not). Transplant-related mortality in this heterogenous group of patients (including high-risk and advanced disease) was 22% at 12 months. It is proposed that treatment of peripheral blood stem cells with CAMPATH-1H is a simple and effective method for depleting T cells which may be applicable to both autologous and allogeneic transplants from related or unrelated donors. Special advantages of this approach are the simultaneous depletion of donor B cells (which reduces the risk of EBV-associated lymphoproliferative disease) and the concomitant infusion of CAMPATH-1H to deplete residual recipient T cells and thus prevent graft rejection. Bone Marrow Transplantation (2000) 26, 69–76.

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Acknowledgements

Antibody production for these studies was supported by the UK Medical Research Council, LeukoSite Inc, and EP Abraham‘s Trust. We are indebted to many colleagues who played an important part in the production of antibodies, care of patients, data collection and analysis, including the staff of the Therapeutic Antibody Centre, University of Oxford, also Bernard Chapuis, Claudine Helg, Corinne Charrin, Colette Grand, and Kate Schoonooghe.

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Authors and Affiliations

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

    G Hale, P Bird & H Waldmann

  2. Constantiaberg Medi-Clinic, Cape Town, South Africa

    P Jacobs & L Wood

  3. Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands

    WE Fibbe

  4. Department of Hematology, Groote Schuur Hospital and the Leukaemia Unit, University of Cape Town, Cape Town, South Africa

    R Barge, N Novitzky, Cdu Toit, L Abrahams & V Thomas

  5. Bone Marrow Transplant Unit, Ulm University Hospital, Ulm, Germany

    D Bunjes, C Duncker & M Wiesneth

  6. Department of Hematology, A-Z St Jan, Brugge, Belgium

    D Selleslag & M Hidajat

  7. Department of Hematology, Hopital Cantonal, Geneva, Switzerland

    M Starobinski

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  1. G Hale
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Hale, G., Jacobs, P., Wood, L. et al. CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells. Bone Marrow Transplant 26, 69–76 (2000). https://doi.org/10.1038/sj.bmt.1702477

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