Fatal graft-versus-host disease associated with solid-organ transplantation

Graft versus host disease (GVHD) is an important and under-diagnosed cause of mortality associated with liver transplantation. We identified 12 cases of GVHD in our experience with 1082 liver transplants performed at our institution between 1991and 1998. All but one of the patients died; GVHD accounted for 5% of the deaths occurring during the first year after transplantation. Patients typically developed fever, skin rash, diarrhea, or pancytopenia within 2 to 6 weeks after their transplant. Early in its course, GVHD was difficult to distinguish from CMV disease, bacterial infection or drug reactions. The diagnosis was usually confirmed by sérologie typing of recipient blood T lymphocytes for donor HLA antigens. A variety of treatments were applied including modulation of immune suppression (both greater and lesser) and hematopoietic cytokines (GCSF, GM-CSF). Most patients died from infections. To identify risk factors for severe GVHD, a retrospective analysis was performed comparing the index cases to the rest of our institutional experience: Closely HLA matched recipients, recipients older than 65 years, and recipients whose donors were more than 40 years younger were at higher risk of developing GVHD. The highest risk (22%) occurred in those patients who had one or fewer HLA A, B mismatches and shared at least one HLA DR antigen with their donor. These data suggest that immunologie "blinding" (by HLA matching) and recipient immunocompelence play important roles. This conclusion is further supported by one of our cases which occurred in a patient with congenital immune deficiency. Conclusions: Liver transplant associated GVHD (LTx-GVHD) is a progressive and seemingly irreversible disease process that, once established, is highly fatal. Future approaches should focus on prevention: These might include treatment of the donor to reduce the number of lymphocytes or reduced immunosuppression of the patient in the early post-transplant period. It may also be important to avoid very close HLA matching when using living related liver donors.