CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells
- 1 July 2000
- journal article
- research article
- Published by Springer Science and Business Media LLC in Bone Marrow Transplantation
- Vol. 26 (1), 69-76
- https://doi.org/10.1038/sj.bmt.1702477
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.Keywords
This publication has 25 references indexed in Scilit:
- Selective removal of alloreactive cells from haematopoietic stem cell grafts: graft engineering for GVHD prophylaxisBone Marrow Transplantation, 1999
- EX VIVO DEPLETION OF T CELLS FROM BONE MARROW GRAFTS WITH CAMPATH-1 IN ACUTE LEUKEMIATransplantation, 1999
- Allogeneic transplantation of selected CD34+ cells from peripheral blood: experience of 62 cases using immunoadsorption or immunomagnetic techniqueBone Marrow Transplantation, 1998
- Campath-1 Antigen (CD52)Published by Elsevier BV ,1998
- Subcutaneous CAMPATH‐1H in fludarabine‐resistant/relapsed chronic lymphocytic and B‐prolymphocytic leukaemiaBritish Journal of Haematology, 1997
- CAMPATH-1 Monoclonal Antibodies in Bone Marrow TransplantationJournal of Hematotherapy, 1994
- IN VIVO CELL ACTIVATION FOLLOWING OKT3 ADMINISTRATIONTransplantation, 1990
- Bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: importance of a graft‐versus‐leukaemia effectBritish Journal of Haematology, 1988
- EVIDENCE FOR THE INVOLVEMENT OF HOST-DERIVED OKT8-POSITIVE T CELLS IN THE REJECTION OF T-DEPLETED, HLA-IDENTICAL BONE MARROW GRAFTSTransplantation, 1987
- The Depletion of T Cell Subsets in Vitro and in VivoTransplantation, 1986