Failure of Fluconazole Prophylaxis to Reduce Mortality During Treatment for Refractory Acute Myeloid Leukemia: Results of a Phase III Multicenter Study

The current randomized study was initiated to assess the efficacy of fluconazole as systemic antifungal prophylaxis in high-risk patients with relapsed acute myeloid leukemia (AML) undergoing intensive reinduction therapy. From 68 fully evaluable patients 36 were randomized for fluconazole and 32 to the control group. No major differences 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%; p = 0.09) mainly due to a higher incidence of bacteremias (42 vs. 22%; p = 0.07). There were two cases of proven invasive fungal infections in each group. Systemic amphotericin B was applied more frequently to patients receiving fluconazole prophylaxis (56 vs. 28%; p = 0.02). There was no impact of fluconazole prophylaxis on the rate of early death or on overall survival. In patients with high-risk relapsed AML undergoing intensive salvage therapy the general use of fluconazole as antifungal prophylaxis can therefore not be supported.