Introduction: Primary prevention of invasive fungal infections (IFI) is a clinically relevant goal in patients with Acute Myeloid Leukemia candidate to allogeneic transplantation. In such population, the greatest proportion of IFI occurs during aplasia following induction chemotherapy (Pagano et al., 2010).
Micafungin (MICA) may be an effective antifungal agent since it has activity against all major Candida spp. and it demonstrates in vitro and in vivo activity against Aspergillus spp.
Aim: to investigate the incidence of IFI occurring in pts with newly diagnosed AML undergoing induction chemotherapy (IC) receiving MICA as antifungal primary prophylaxis (APP).
Materials (or patients) and methods: Since July 2011 to October 2014, we prospectively treated 40 consecutive pts with newly diagnosed AML: 20/40 pts were treated with “3+7” IC, 12/40 pts with “FLAI” IC, 8/40 pts with “ICE” IC. MICA was started 1 day following the end of IC at the daily dose of 50 mg i.v. MICA was continued until neutrophil engraftment (PMN>0.5x10^9/L for 3 consecutive days). Galactomannan was measured once a week using ELISA test and results were considered positive if ≥0.5 in serum. IFI was defined as possible, proven or probable according to 2008 EORTC/MSG definitions.
Results: None of our patients discontinued the treatment for drug-related adverse events. 30/40 pts concluded MICA treatment at neutrophil engraftment without signs of IFI. 10/40 pts (25%) switched to an alternative antifungal therapy as empirical treatment. Of these, possible (n=4), probable (n=3) and proven (n=1) IFI were diagnosed. Probable IFIs were pulmonary infections, 1 candidiasis and 2 invasive aspergillosis were diagnosed and treated with liposomal B amphotericine or voriconazole. The only proven IFI was a disseminated fusariosis treated with a combination of liposomal B amphotericine and voriconazole.
All pts were neutropenic at the onset of IFI with a median duration of neutropenia of 31 days (14–73). All of them resolved the infection at neutrophil recovery after IC.
Conclusion: In this 3-year study in 40 patients breakthrough proven or probable IFI occurred in 10%. This result is comparable with randomized clinical trials and several observational studies focused on posaconazole prophylaxis (graded A-I by the European Conference on Infections in Leukemia - ECIL- for antifungal primary prophylaxis during induction chemotherapy) which found breakthrough IFI ranging from 0 to 17%. Micafungin primary antifungal prophylaxis is safe and effective during induction chemotherapy in patients with AML candidate to allogeneic transplantation.
Full conference title:
- EBMT 41st (2015)