Antifungal Prophylaxis and Treatment of Breakthrough Invasive Fungal Diseases in High-Risk Hematology Patients: A Prospective Observational Multicenter Study

Abstract

We aimed to investigate the approaches for antifungal prophylaxis (AFP) and antifungal treatment in breakthrough invasive fungal diseases (IFDs) under AFP in high-risk hematology patients. Patients >= 18-years who received chemotherapy for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or a conditioning regimen for allogeneic hematopoietic stem cell transplantation (AHSCT) with a duration of neutropenia (< 500 cells/mm(3)) >= 10 days were included in a prospective multicenter observational study. Patients were followed until one week after recovery from neutropenia, discharge from the hospital, or death, which comes first to define the success of AFP. A total of 230 patients were recruited from 18 centers in seven months. Posaconazole prophylaxis was used in 134 (44 of whom failed) and 96 patients received fluconazole (28 of whom failed). The survival rate at 12 weeks after the initiation of AFP was higher in patients with successful prophylaxis (96.2% vs 56.9%, p < 0.001). IFDs were diagnosed in 27 patients. Duration of neutropenia was the only risk factor (OR: 1.03; 95% CI: 1.004-1.053) for development of IFDs. The types of breakthrough IFDs were; possible IFD in 15 patients, probable invasive aspergillosis (IA) in 9 patients, proven IA in 2 patients; and proven mucormycosis in 1 patient. Voriconazole was the drug of choice in 16 patients (5 of whom failed). Liposomal amphotericin B was used in the treatment of 8 patients (4 of whom failed). Posaconazole was the most frequently prescribed AFP in AML patients with high compliance to international guidelines. Approximately, one-third of ALL patients and AHSCT recipients received off-label posaconazole prophylaxis.