Graft-versus-host disease after autologous bone marrow transplantation: a realistic expectation?

ABSTRACT

The immunobiological mechanisms involved in the manifestation of an autoaggressive disease after autologous bone marrow transplantation (BMT) and cyclosporine A (CyA) treatment are still unclear. This disease, which in animals shows clinical and histopathological features in the skin, liver and gut similar to those of graft-versus-host disease (GVHD), is called autologous GVHD and associated with the appearance of CD8+ cells with a lytic specificity for a public epitope on MHC class II. 2 steps are supposed to be essential for the induction of autologous GVHD firstly, the elimination of a host resistance or an autoregulatory mechanism of self tolerance by high dose chemotherapy including total body irradiation, and secondly, the prevention of clonal deletion of MHC class II-restricted auto-reactive T-cells by CyA. Several experiments describe a possible antitumor effect of this disease in vitro as well as in vivo. The CD8+ cells kill tumor cells in vitro and survival of animals with autologous GVHD challenged with low doses of tumor cells is better than that of animals without autologous GVHD. In an attempt to reduce the relapse rate after autologous BMT, induction of GVHD with CyA treatment was investigated in clinical trials. A syndrome similar to the one described in rats was observed also in humans. However, symptoms were confined to the skin, appeared earlier than in experimental transplantation and were always self-limiting. Further investigations aiming at understanding in more detail the immunobiological mechanisms in human autologous GVHD and phase III clinical trials will have to be completed in order to define the role of this disease in clinical transplantation.