Graft-versus-host disease after marrow transplantation.

In random bred species including dog and man, a marrow graft from a donor genetically identical for the major histocompatibility complex is followed by significant graft-versus-host disease (GVHD) in 30% to 50% of the recipients despite the administration of postgrafting immunosuppression. Controlled trials comparing the immunosuppressive drugs methotrexate or cyclosporine have shown no differences in long-term survival, although cyclosporine reduces the incidence of mucositis and is associated with somewhat earlier engraftment. Observations in the canine model indicating efficacy of combining a brief course of methotrexate with the cyclosporine regimen are now being confirmed in patients with early results indicating a reduction in GVHD and an improved survival. In both species failure to administer immunosuppression after grafting is associated with a high incidence of acute GVHD and an adverse effect on survival. Removal of donor T cells from the marrow inoculum reduces the incidence of acute GVHD but at the risk of a higher likelihood of subsequent graft failure and maybe even leukemic recurrence. Results of studies in canine and human chimeras agree with murine data indicating a principal role for T cells in the pathogenic mechanism of GVHD. Chimera lymphocytes (of donor origin) from dogs and patients with acute GVHD show proliferative responses to previously stored host cells, and lymphocytes cytotoxic to host target cells are seen in patients with GVHD. Observations indicate a direct, rather than an indirect, role for T cells in GVHD. "Specific" suppressor cells may be responsible for maintaining stable graft-host tolerance while "nonspecific" suppressor cells may play a role in the impaired immune defenses in patients with chronic GVHD. Chronic GVHD, which resembles systemic collagen vascular disease, occurs in approximately 40% of HLA-identical recipients, particularly following acute GVHD and is more frequent in older patients. Efforts to treat both acute and chronic GVHD with prednisone, antithymocyte globulin, cyclosporine and azathioprine are only unpredictably effective. Data in dogs pointed out the feasibility of transplants from partially matched related donors or matched unrelated donors, an approach that is now being pursued in human patients. Marrow grafts from HLA-partially matched family members resulted in a higher incidence of acute GVHD. There was no difference in acute GVHD comparing class I to class II antigen differences and long term survival was influenced by patient age and disease status rather than HLA incompatibility.(ABSTRACT TRUNCATED AT 400 WORDS)