Evaluation on 'real life' prescriptions of antifungal prophylaxis in acute myeloid leukemia: Final results from a prospective survey

Objectives: To describe the current use of antifungal (AF) prophylaxis in consecutive, unselected adult patient with acute myeloid leukemia patients (AMLs) at first induction of remission and to analyze the efficacy of prophylaxis with posaconazole (POSA) when compared to itraconazole (ITRA) in a ‘real life’ setting. Methods: From January 2010 to September 2011, all newly diagnosed AMLs have been consecutively registered and prospectively monitored in 30 Italian participating centers. In order to minimize evaluation bias, our analysis focused on adult cases that: (1) received intensive chemotherapy; (2) received a mold-active AF prophylaxis for at least 7 days. Principal demographic and clinical data, as well as antifungal treatments were collected. To determine prophylaxis efficacy, IFDs incidence, IFD-attributable mortality and overall survival were evaluated. Results: During the study period 703 pts received conventional chemotherapy as first induction for AML. 508 pts were finally included in the present analysis. POSA was the most frequently employed drug (260/508, 51%), followed by fluconazole (148, 29%) and itraconazole (93, 18%). Remaining 7 patients (1%) had received other antifungal agents (5 voriconazole, 1 caspofungin and 1 liposomal amphotericin B). When comparing the POSA group to those receiving ITRA no significant differences emerged in terms of the main risk factors for IFDs. In particular the 2 groups resulted to be comparable in terms of age, sex, frequency and duration of deep neutropenia, days of prophylaxis. On the contrary, there were significant differences in breakthrough IFDs (18.9% in POSA vs 38.7% in ITRA, Pvalue < 0.001). The same advantages emerged also when considering proven/probable mold infections only (POSA 2.7% vs ITRA 8.6%, P 0.001). Caspofungin and amphotericin B compounds were the most frequently employed drugs, as empirical/pre-emptive treatments. There were no significant differences in the IFDs attributable mortality rate, while POSA prophylaxis resulted to significantly impact 90th day overall survival (P 0.002). Conclusions: During the last few years the use of POSA prophylaxis in high risk pts has significantly increased. Although not randomized, our study demonstrates in a ‘real life’ setting the increased use and the higher efficacy of POSA prophylaxis, when compared to ITRA. Previous POSA prophylaxis confers an advantage both in terms of breakthrough IFDs and overall survival