Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study

Abstract

A complete list of the members of the VOSIFI Study Group is provided in the Appendix. BackgroundRecurrence of prior invasive fungal infection (relapse rate of 30-50%) limits the success of stem cell transplantation. Secondary prophylaxis could reduce disease burden and improve survival. Design and MethodsA prospective, open-label, multicenter trial was conducted evaluating voriconazole (4 mg/kg/12 h intravenously or 200 mg/12 h orally) as secondary antifungal prophylaxis in allogeneic stem cell transplant recipients with previous proven or probable invasive fungal infection. Voriconazole was started 48 h or more after completion of conditioning chemotherapy and was planned to be continued for 100-150 days. Patients were followed for 12 months. The primary end-point of the study was the incidence of proven or probable invasive fungal infection. ResultsForty-five patients were enrolled, 41 of whom had acute leukemia. Previous invasive fungal infections were proven or probable aspergillosis (n=31), proven candidiasis (n=5) and other proven or probable infections (n=6); prior infection could not be confirmed in three patients. The median duration of voriconazole prophylaxis was 94 days. Eleven patients (24%) died within 12 months of transplantation, but only one due to systemic fungal disease. Three invasive fungal infections occurred post-transplant: two relapses (one candidemia and one fatal scedosporiosis) and one new zygomycosis in a patient with previous aspergillosis. The 1-year cumulative incidence of invasive fungal disease was 6.7±3.6%. Two patients were withdrawn from the study due to treatment-related adverse events (i.e. liver toxicity). ConclusionsVoriconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after allogeneic stem cell transplantation. The observed incidence of 6.7% (with one attributable death) is considerably lower than the relapse rate reported in historical controls, thus suggesting that voriconazole is a promising prophylactic agent in this population. (ClinicalTrials.gov identifier: NCT00143312). © F e r r a t a S t o r t i F o u n d a t i o n

The impact of prior invasive mold infections in leukemia patients who undergo allo-SCT in the era of triazole-based secondary prophylaxis

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Invasive aspergillosis in children after haematopoietic stem cell transplantation

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