Towards rational graft-versus-host disease prophylaxis.

Calcineurin inhibition for graft-versus-host disease (GvHD) prophylaxis was introduced into clinical practice of bone marrow transplantation about 35 years ago. Through the early work of Storb, Deeg and Ringden it became clear that calcineurin inhibition with cyclosporine A as a single agent was more effective than methotrexate alone and that the two drugs acted synergistically (see Table 1 for overview). Since then, multiple strategies have been tested in randomized trials: modified doses of cyclosporine A and another calcineurin inhibitor (tacrolimus), T-cell depletion (antithymocyte globulin, CD8 antibodies), cytokine blockade (CD1 antibodies, CD25