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

Abstract

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. Am. J. Hematol. 88:283–288, 2013. © 2013 Wiley Periodicals, Inc.

Primary prophylaxis of invasive fungal infections with posaconazole or itraconazole in patients with acute myeloid leukaemia or high‐risk myelodysplastic syndromes undergoing intensive cytotoxic chemotherapy: A real‐world comparison

“…[27][28][29] Importantly, preemptive therapy based on the result of GM assessments and/or result of thoracic CT scans has been challenged by previous studies which have shown that anti-mould prophylaxis with posaconazole may disturb GM antigen expression. 29,30 Specifically, posaconazole may reduce the "window of positivity"…”

Acute myeloid leukaemia: challenges and real world data from India

“…Fungal infections following induction chemotherapy are recognized to be associated with increased early mortality and to have an adverse impact on long‐term survival in patients with AML (Girmenia et al , ). The proportion of patients developing proven and probable IFI in AML following induction chemotherapy varies from 14% to 22% (Barreto et al , ; Gomes et al , ). In our series 28% of patients had evidence of possible or proven IFI.…”

Invasive fungal infection following chemotherapy for acute myeloid leukaemia—Experience from a developing country

“…Mortality related to fungal infections remains at about 20%‐30% and is an important reason for treatment failure in patients undergoing chemotherapy for AML . Antifungal prophylaxis has played an important role in reducing the incidence of IFIs in patients undergoing chemotherapy for AML . In developing countries, the additional challenges include recurrent constructions that occur routinely within the hospital and the absence of HEPA‐filtered rooms for chemotherapy, both of which have been proven to be factors influencing fungal infections .…”