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

Graft-versus-host disease (GVHD) is a major cause of mortality and morbidit y after allogeneic bone marrow transplantation, but can be avoided by remov ing T lymphocytes from the donor bone marrow. However, T cell depletion inc reases 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 pe ripheral blood (PBSC), (2) admixture with a CD52 monoclonal antibody in ord er 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 sis centers receive d PBSC transplants from HLA-matched siblings between 1997 and 1999, A wide spectrum of diseases, both malignant and non-malignant, was included. The r ecovery of CD34(+) cells after antibody treatment was close to 100%. The ri sk of acute GVHD (grade 2 to 4) was 11% in the CAMPATH-1G group and 4% in t he CAMPATH-1H group (P = NS), The risk of chronic GVHD (any grade) was 11% in the CAMPATH-1G group and 11% in the CAMPATH-1H group (P = 0.03) but the risk of extensive chronic GVI-ID was only 2%. The overall risk of graft fai lure/rejection was 2%, not significantly different between the two antibodi es. Antibody treatment was equally effective at concentrations between 10 m u g/ml and 120 mu g/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 pati ents (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 do nors. Special advantages of this approach are the simultaneous depletion of donor B cells (which reduces the risk of EBV-associated lymphoproliferativ e disease) and the concomitant infusion of CAMPATH-1H to deplete residual r ecipient T cells and thus prevent graft rejection.