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To determine the relation between the serum cyclosporine concentration and the risk of acute graft-versus-host disease (GVHD), we studied 179 recipients of bone marrow grafts from HLA-identical sibling donors who received prophylaxis with cyclosporine, either by itself or combined with methotrexate. Cyclosporine was given either orally or intravenously at full doses from the day before transplantation until day 50; it was then tapered off and discontinued on day 180. Trough concentrations of serum cyclosporine were measured by radioimmunoassay. The relation between patients' characteristics and the risk of acute GVHD was analyzed with a relative-risk regression model. In 66 patients (37 percent), grades II to IV of acute GVHD developed 7 to 66 days (median, 13) after transplantation. The trough cyclosporine concentration for a given week was significantly associated with the risk that acute GVHD would develop during the following week. The relative risks were 0.7 (i.e., there was a 30 percent reduction in risk) for every increase of 100 ng per milliliter in cyclosporine concentration and 1.0, 0.60, and 0.20 for concentrations of less than 100, 100 to 199, and 200 or more ng per milliliter, respectively (P less than 0.01). A patient's age, prophylaxis regimen, and year of transplantation also influenced the risk of acute GVHD significantly. These data indicate that low cyclosporine concentrations can be a cause of treatment failure and that concentrations should be monitored in recipients of marrow transplants.
Yee et al. (Thu,) studied this question.