Haematologica (Oct 2010)

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

  • Catherine Cordonnier,
  • Montserrat Rovira,
  • Johan Maertens,
  • Eduardo Olavarria,
  • Catherine Faucher,
  • Karin Bilger,
  • Arnaud Pigneux,
  • Oliver A Cornely,
  • Andrew J. Ullmann,
  • Rodrigo Martino Bofarull,
  • Rafael de la Cámara,
  • Maja Weisser,
  • Effie Liakopoulou,
  • Manuel Abecasis,
  • Claus Peter Heussel,
  • Marc Pineau,
  • Per Ljungman,
  • Hermann Einsele

DOI
https://doi.org/10.3324/haematol.2009.020073
Journal volume & issue
Vol. 95, no. 10

Abstract

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Background Recurrence 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 Methods A 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.Results Forty-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 Two patients were withdrawn from the study due to treatment-related adverse events (i.e. liver toxicity).Conclusions Voriconazole appears to be safe and effective for secondary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.