Outcome with Early Oral Voriconazole Therapy in 73 AML-MDS Patients with Invasive Aspergillosis

Bart Rijnders, Lennert Slobbe, Pieternella Lugtenburg, Jeanette Doorduijn.

Author address: 

Erasmus MC, Dept. of Internal Medicine, Section of Infectious Diseases, Rotterdam, the Netherlands

Abstract: 

Background: Invasive aspergillosis (IA) is a leading cause of morbidity and mortality in patients with AML/MDS. Current standard of care is treatment with voriconazole. In the registration trial voriconazole was given intravenously for the first 8 days but the bioavailability of oral voriconazole is excellent. Therefore we decided to give voriconazole orally during the first 8 days of therapy if oral intake was possible. We here describe our experience in a large group of patients with AML/MDS and IA. Methods: In 269 consecutive patients treated for AML/MDS from 2002 to 2007, evidence for IA was collected using HRCT for the evaluation of neutropenic fever and galactomannan measurement in broncho-alveolar lavage fluid of intrapulmonary lesions. IA was classified according to the recently updated EORTC-MSG definitions. All cause mortality 12 weeks after the start of antifungal therapy was registered. For the evaluation of attributable mortality of IA we compared all cause mortality 12 weeks after the last course of anti-leukemic therapy between patients with and without IA. Voriconazole treatment was given orally from day 1 whenever oral intake was possible. The same dosing regimen as was given intravenously in the study by Herbrecht et al was used orally (Herbrecht R et al. 2002). Results: 80 patients developed IA, 48 (18%) of them had probable or proven infection and 32 (12%) had possible IA. 6 were treated with amphotericin-B in 2002 before voriconazole became available in the Netherlands and 1 patient received itraconazole. 73 patients were treated with voriconazole; 55 (75%) were able to take oral voriconazole from day 1. Overall mortality 12 weeks after the start of voriconazole was 22% (16/73). This compares favourably with the study by Herbrecht et al. where a 12 week overall mortality of 29% was reported with voriconazole and 42% when amphotericin-B deoxycholate was used. The overall mortality 12 weeks after the last course of anti-leukemic therapy was 26% in IA-patients compared to 16% in IA-free patients (p=0.06) with a hazard ratio of dying for patients with IA of 2.4 (95% CI, 1.3 -4.4) in a cox regression analysis. Conclusions: Early diagnosis with HRCT, galactomannan measurement in BAL and treatment of IA with oral voriconazole results in an acceptable 12-week mortality. Reference: Herbrecht R et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002 Aug 8;347(6):408-15.
2008

abstract No: 

S73

Full conference title: 

15th International Symposium on Infections in the Immunocompromised Host
    • ISIIH 15th