Prediction of systemic fungal infection in allogeneic marrow recipients: impact of amphotericin prophylaxis in high-risk patients

PURPOSE To identify risk factors that might predict for systemic fungal infections in marrow transplant recipients within the first 100 days and to assess the efficacy of low-dose amphotericin B used as prophylaxis for candidemia and infection with invasive Aspergillus species in patients at risk. PATIENTS AND METHODS A retrospective analysis of transplant outcomes for 331 allogeneic marrow recipients transplanted between 1983 and 1989 was performed to identify patients who might be at increased risk of fungal infection. Factors analyzed included disease, remission status, transplant regimen, graft-versus-host disease (GVHD) prophylaxis, duration of neutropenia, and development of GVHD. A trial of low-dose amphotericin (5 to 10 mg/d) begun on day +1 and continuing for 2 to 3 months posttransplant was begun in 1987 to evaluate its utility in reducing systemic mycoses. RESULTS There were 18 episodes of candidemia and 18 systemic mycoses documented by blood or tissue culture or by biopsy. The initiation of high-dose (0.5 to 1 mg/kg/d) corticosteroids early as a component of GVHD prophylaxis in 1986 was identified as the most important risk factor for fungal infections, with a sixfold increase in infections as compared with the previous GVHD regimen (P < .0001); this was despite a significant decrease in the incidence of grade II to IV GVHD (7% v 43%; P = .0001). Low-dose amphotericin B initiated before the start of high-dose corticosteroid GVHD prophylaxis reduced the incidence of fungal infections from 30% to 9% (P = .01) without renal toxicity. Cyclosporine levels were lower in the patients who received amphotericin, leading to an increase in the rate of GVHD to 19% (P = .02). Controlling for GVHD prophylaxis, prolonged neutropenia (P = .00), and grade II to IV GVHD (P = .01) were also identified as risk factors for fungal infection. CONCLUSION Amphotericin B can be used in low doses as prophylaxis for fungal infections early in the posttransplant course. However, cyclosporine doses need to be monitored to maintain target levels.