Failure of fluconazole prophylaxis to reduce mortality or the requirement of systemic amphotericin B therapy during treatment for refractory acute myeloid leukemia : Results of a prospective randomized phase III study

BACKGROUND. Invasive fungal infections have increasingly become a matter of concern with regard to patients receiving intensive myelosuppressive therapy for hematologic malignancies. Such infections, especially prolonged neutropenia systemic fungal infections, may contribute substantially to infectious complications and early death. Measures for early detection and effective prophylactic strategies using active and nontoxic antifungal agents are therefore urgently needed. METHODS. The current randomized study was initiated to assess the efficacy of oral fluconazole as systemic antifungal prophylaxis for high risk patients with recurrent acute myeloid leukemia undergoing intensive salvage therapy. RESULTS. Of 68 fully evaluable patients, 36 were randomized to fluconazole in addition to standard prophylaxis with oral co-trimoxazol, colistin sulphate, and amphotericin B suspension, and 32 were randomized to standard prophylaxis only. No major differences between the two groups were observed in the number of episodes of fever of unknown origin (61% vs. 50%) or clinically defined infections (56% vs. 50%). Microbiologically defined infections were more frequent in the fluconazole group (50% vs. 31%), mainly due to a higher incidence of bacteremias (42% vs. 22%). There were two cases of proven invasive fungal infections in each group. Systemic amphotericin B was administered more frequently to patients receiving fluconazole prophylaxis (56% vs. 28%). Fluconazole prophylaxis had no impact on the rate of early death or overall survival. CONCLUSIONS. For patients with high risk recurrent acute myeloid leukemia undergoing intensive salvage therapy, antifungal prophylaxis with fluconazole was not superior to standard prophylaxis only.