Purpose: We identified the clinical characteristics including disease status for expecting success outcome of empirical antifungal therapy for invasive fungal infection (IFI) using itraconazole in immunocompromised patients with haematological malignancies. Methods: The prospective multicenter observational study was performed at 26 medical centers for 9 months. Results: 376 patients (median age 48) were enrolled and analyzed. The patients with possible and probable categories for IFI according to the EORTC/MSG criteria were included. We excluded the patients with proven IFI. IV itraconazole was administered as routine schedule, followed by oral itraconazole solution. Underlying disease consisted of 61% of AML and 15% of ALL. Overall success rate of empirical antifungal therapy with itraconazole was 196/376 (51%). Acute leukemia in non-CR status and advanced stage of MDS patients showed a lower trend of success rate. Combined co-morbidities, underlying lung disease, poor ECOG performance status (≥ 2), abnormal chest X-ray at the time of initiation of empirical antifungal therapy, no early initiation of empirical antifungal therapy (the duration of baseline neutropenic fever ≥ 3 days) and antifungal prophylaxis other than itraconazole were associated with decreased overall success rate. Multivariate analysis revealed that poor performance status (≥ 2) (HR=1.9) and abnormal chest X-ray (HR=2.0) were significantly associated with poor outcome of empirical antifungal therapy. Overall success rate of empirical antifungal therapy was not affected by antifungal prophylaxis. Defervescence in setting of neutropenia was 70% (264/276). Higher rate of defervescence was observed in the patients with early stage of MDS (92% vs. 40%, P = 0.02). Median time to defervescence after empirical itraconazole therapy was 3 days. Short mean time to defervescence was observed in the patients with acute leukemia in CR status (P = 0.002) or early stage of lymphoid malignancies (P = 0.03). The rate of breakthrough fungal infection was 4% (16/376). Breakthrough Aspergillus infection was documented in the half of theses patients (8/16). Conclusions: IV itraconazole followed by oral itraconazole solution is an effective regimen for empirical antifungal therapy. Poor performance status and abnormal chest X-ray were predictive factors for failure of empirical antifungal therapy.
Full conference title:
4th Advances Against Aspergillosis
- AAA 4th (2010)