Mechanisms and avoidance of graft-versus-host disease

In the past 2 years, efforts in clinical bone marrow transplantation seem to have increased by the fact that several new centers, both in the U.S. and in Europe, have initiated a bone marrow transplantation program and others are preparing to do so. The graft versus-host reaction (GVHR) or disease (GVHD) remains to be a severe limitation to the success and to a more general application of bone marrow grafting. For the treatment of severe combined immune deficiency (SCID), the very satisfactory results remain restricted to the minority of the cases, namely those for which a major histocompatibility complex (MHC) matched sibling donor is available. The optimism created by a few successful reconstructions with liver cells from very young fetuses has not held up, and unrelated or nonsibling bone marrow cannot yet be used as a routine for lack of insight in the genetic factors that determine GVHD. In aplastic patiens, slightly more effective conditioning regimens have improved the take rate of MHC-matched bone marrow, but by the same token, the proportion of patients suffering from GVHD has increased. For lack of an MHC-identical sibling, the majority of aplastic and leukemic patients cannot be grafted, since the problem of achieving a high proportion of takes with MHC-mismatched bone marrow has not been solved. For the treatment of leukemia, the even higher incidence of GVHD in this category of patients has not been improved by any of the currently employed prophylactic or therapeutic measures. Clearly, much more fundamental knowledge has to be obtained in order to solve this problem, and the challenge is increasing under pressure from clinical interest. Yet, steady progress is being made by a number of modifications of conditioning regimens, by increasing insight in the histocompatibility factors governing take and GVDH. In addition, refinement of methodology of selective removal or inactivation of lymphocytes is taking place as an approach to diminish the risks of development of GVHD.