Voriconazole for Salvage Therapy of Fungal Infections in Patients with Hematological Malignancies and Stem Cell Transplantation



Background: Voriconazole (vori) has activity against both non-albicans Candida and moulds. We report our experience with this drag used for salvage therapy of invasive fungal infections is 24 patients treated in a single stem cell transplant (SCI) center. Methods: Twenty patients were enrolled is an open label phase III 'salvage' protocol and 4 patients were provided with drug by compassionate use. Patients had either failed or were intolerant to amphotericin B (AMB). Fungal infections were defined as proven or probable according to published criteria. Failure, partial or complete response (PR, CR) was determined by clinical, radiographic, and mycologic criteria at the end of vori therapy. Results: Fourteen of 24 (58%) patients had received allogeneic stem cell transplants (SCT), 5 (21%) autologous, and S (21%) were pre-SCT. Of 26 invasive infections, l l (42°l0) were proven invasive aspergillosis (IA), 12 (46%) probable IA, 2 invasive candidiasis, and 1 Pseudoallescheria. Over 70% of patients received lipid amB prior to vori. Patients were treated with vori for a mean duration of 7.1 weeks. The most common vori toxicity was blurred vision (3/24, 12.5%). Eight of 24 (33%) were judged to have KR, 2 (8%) partial response, and 14 (58%) failure. Complete or partial responses occurred in patients who had infection diagnoses pre-SCT (ono, 40°10), infection after autologous or mini allogeneic SCT (2/10, 20%>, invasive disease involving the sinuses (2110, 2D%), and disseminated candidiasis (2110, 20%). Three of 14 (29 %) allograft recipients with proven IA ( I pulmonary IA, 2 sinus !A) had a CR or PR. All allogaft recipients on steroids with proven pulmonary IA failed therapy and died. Conclusions: Vori is well tolerated is SCT patients, and appears to have some activity in patients who fail amB. Outcome of proven infections, particularly IA in all allogenic SCT patients is poor. Efficacy of vori administered early after diagnosis of invasive fungal infections awaits results of an ongoing randomized trial.

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IDSA 38th
    • IDSA 38th