The incidence of invasive fungal infections in neutropenic patients with acute leukemia and myelodysplastic syndromes receiving primary antifungal prophylaxis with voriconazole

The objective of this study is to characterize the outcomes of primary antifungal prophylaxis with voriconazole in patients receiving intensive chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). We conducted a single center, retrospective, cohort study of consecutive adult patients with AML or MDS at Mayo Clinic between January 1, 2006 and July 1, 2010. The study included patients undergoing induction or first relapse combination chemotherapy who received voriconazole 200 mg orally twice daily as prophylaxis during the neutropenic phase. Patient records were evaluated until 30 days after neutrophil recovery for development of invasive fungal infection (IFI) as defined per EORTC/MSG 2008 criteria with computed tomography scans independently reviewed by a radiologist. Therapeutic drug monitoring and reasons for voriconazole discontinuation were documented. Twenty four episodes of IFI were detected among 165 consecutive patients for an overall incidence of 145 per 1000 patients. The incidence of IFI was 24, 42, and 78 per 1000 patients for proven, probable, and possible infection, respectively. Four patients developed proven IFI (n=2 Aspergillus spp., n=2 Rhizopus spp.). Serum voriconazole trough concentrations were available in 39 patients, and no statistically significant difference in voriconazole trough level was observed between those with versus without an IFI. Voriconazole prophylaxis was discontinued in 81 patients due to suspected IFI (n=24), fever of unknown origin (n=19), adverse events (n=23), and other causes (n=17). Voriconazole as primary IFI prophylaxis is safe and may be beneficial in AML/MDS patients receiving intensive chemotherapy.