[Use of monoclonal antibodies for the prevention of graft-versus-host and host-versus-graft reaction in allogenic bone marrow grafts]

Abstract

The graft-versus-host (GvH) reaction remains one of the major complications in allogeneic bone-marrow (BM) grafting, in spite of prophylactic treatments such as methotrexate and Cyclosporine-A. It is admitted that T lymphocytes of graft origin become the effector cells reacting against the host tissues. It is possible to deplete the vast majority of T cells from the BM inoculum using monoclonal antibodies (MoAb) of the anti-pan T specificity. The two most currently used methods are the complement-dependent cytolysis and the use of immunotoxins (MoAb combined to ricin). The T cell depletion is the most effective procedure for the prevention of GvH (less than 10% versus 40 to 60% in the historical series). However, this mode of prevention can induce resistance phenomena towards the graft acceptance (15 to 20% of cases). This complication can be prevented by the in vivo use of MoAb specific for the host's radioresistant cells. Another alternative way consists in the reinforcement of conditioning aiming both at the elimination of residual immunocompetent cells and at a more efficient action upon the imperceptible tumoral mass. The absence of GvH can indeed be accompanied by an increase of recurrent diseases due to the absence of a graft-versus-leukemia (GvL) reaction.