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Antifungal Prophylaxis and Treatment of Breakthrough Invasive Fungal Diseases in High-Risk Hematology Patients: A
Gökhan Metan1, Ayşe Çiftçioğlu2, Rabin Saba3,4
1Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Hacettepe Üniversitesi Tıp Fakültesi Hastanesi, İç Hastalıkları Binası, Enfeksiyon Hastalıkları Ve Klinik Mikrobiyoloji Anabilim Dalı, Sıhhıye, Ankara, Türkiye.
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/mm3) ≥ 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.
Insights
Antifungal prophylaxis (AFP) in high-risk hematology patients improved survival. Breakthrough invasive fungal diseases (IFDs) occurred in 27 patients, with neutropenia duration being a key risk factor.
Area of Science:
- Hematology
- Infectious Diseases
- Pharmacology
Background:
- High-risk hematology patients undergoing chemotherapy or stem cell transplantation are susceptible to invasive fungal diseases (IFDs).
- Antifungal prophylaxis (AFP) is crucial for preventing IFDs in these immunocompromised individuals.
- Understanding the effectiveness of different AFP strategies and treatment outcomes is vital.
Purpose of the Study:
- To investigate antifungal prophylaxis (AFP) approaches and antifungal treatment strategies for breakthrough invasive fungal diseases (IFDs) in high-risk hematology patients.
- To evaluate the success rates of different antifungal agents used for prophylaxis.
- To identify risk factors for the development of IFDs.
Main Methods:
- Prospective, multicenter observational study involving 230 high-risk hematology patients (AML, ALL, AHSCT).
- Patients received either posaconazole or fluconazole for antifungal prophylaxis.
- Follow-up until recovery from neutropenia, discharge, or death to assess AFP success and IFD development.
Main Results:
- Successful AFP was associated with significantly higher 12-week survival rates (96.2% vs. 56.9%).
- Invasive fungal diseases (IFDs) were diagnosed in 27 patients; longer duration of neutropenia was the only identified risk factor.
- Posaconazole was frequently used for AML patients, aligning with guidelines, while off-label use was noted in ALL and AHSCT recipients.
Conclusions:
- Antifungal prophylaxis (AFP) significantly improves survival in high-risk hematology patients.
- Duration of neutropenia is a critical risk factor for breakthrough invasive fungal diseases (IFDs).
- Current AFP practices show variability, particularly regarding off-label posaconazole use in certain patient groups.
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