Retrospective assessment of secondary prophylaxis for invasive aspergillosis in neutropenic hematology patients and identification of risk factors for relapse of fungal disease

Background: Invasive aspergillosis (IA) is a critical complication in neutropenic patients. Recurrent IA is especially associated with high mortality. Therefore, secondary prophylaxis is important in patients with a history of IA. We retrospectively assessed the effect of secondary prophylaxis for IA. Methods: We reviewed the medical records of 46 hematology patients who developed possible, probable, or proven IA according to the EORTC/MSG criteria between 2005 and 2009, and who subsequently underwent chemotherapy (n = 30) or stem cell transplantation (n = 16). Results: Ten patients developed recurrent IA within 10 days after recovery from neutropenia. None of the 15 patients who achieved complete response (CR) of IA experienced recurrent IA. Among patients who did not achieve CR of IA, multivariate analysis identified the following independent risk factors: female sex (hazard ratio (HR) 7.23, 95% confidence interval (CI) 2.38-21.9, p = 0.00047), high serum C-reactive protein level (>= 1 mg/dl) at the beginning of subsequent therapy (HR 4.46, 95% CI 1.51-13.2, p = 0.007), and the use of micafungin (HR 12.0, 95% CI 2.03-71.2, p = 0.0061) or amphotericin B (HR 16.5, 95% CI 1.56-174, p = 0.020) for secondary prophylaxis (reference: voriconazole). Conclusions: Three risk factors for recurrent IA were identified. However, a prospective controlled trial is required to evaluate the impact of secondary prophylactic regimens.