D-Index–Guided Early Antifungal Therapy Versus Empiric Antifungal Therapy for Persistent Febrile Neutropenia: A Randomized Controlled Noninferiority Trial
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- Yoshinobu Kanda
- Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan
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- Shun-ichi Kimura
- Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan
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- Masaki Iino
- Department of Hematology, Yamanashi Prefectural Central Hospital, Kofu, Japan
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- Takahiro Fukuda
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
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- Emiko Sakaida
- Department of Hematology, Chiba University Hospital, Chiba, Japan
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- Tatsuo Oyake
- Division of Hematology and Oncology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan
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- Hiroki Yamaguchi
- Department of Hematology, Nippon Medical School, Tokyo, Japan
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- Shin-ichiro Fujiwara
- Division of Hematology, Department of Medicine, Jichi Medical University, Saitama, Japan
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- Yumi Jo
- Infection Control Division, Department of Oncology and Hematology, Shimane University Hospital, Izumo, Japan
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- Akinao Okamoto
- Department of Hematology, Fujita Health University School of Medicine, Toyoake, Japan
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- Hiroyuki Fujita
- Department of Hematology, Saiseikai Yokohama Nanbu Hospital, Yokohama, Japan
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- Yasushi Takamatsu
- Division of Medical Oncology, Hematology and Infectious Diseases, Department of Internal Medicine, Fukuoka University Hospital, Fukuoka, Japan
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- Yoshio Saburi
- Department of Hematology, Oita Prefectural Hospital, Oita, Japan
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- Itaru Matsumura
- Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka, Japan
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- Jun Yamanouchi
- Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Matsuyama, Japan
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- Souichi Shiratori
- Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan
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- Moritaka Gotoh
- Department of Hematology, Tokyo Medical University, Tokyo, Japan
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- Shingen Nakamura
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
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- Kazuo Tamura
- General Medical Research Center, Fukuoka University, Fukuoka, Japan
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<jats:sec><jats:title>PURPOSE</jats:title><jats:p> Empiric antifungal therapy (EAT) is recommended for persistent febrile neutropenia (FN), but in most patients, it is associated with overtreatment. The D-index, calculated as the area surrounded by the neutrophil curve and the horizontal line at a neutrophil count of 500/μL, reflects both the duration and depth of neutropenia and enables real-time monitoring of the risk of invasive fungal infection in individual patients at no cost. We investigated a novel approach for patients with persistent FN called D-index–guided early antifungal therapy (DET), in which antifungal treatment is postponed until a D-index reaches 5,500 or the detection of positive serum or imaging tests, and compared it with EAT in this multicenter open-label noninferiority randomized controlled trial. </jats:p></jats:sec><jats:sec><jats:title>PATIENTS AND METHODS</jats:title><jats:p> We randomly assigned 423 patients who underwent chemotherapy or hematopoietic stem-cell transplantation for hematologic malignancies to the EAT or DET group. The prophylactic use of antifungal agents other than polyenes, echinocandins, or voriconazole was allowed. Micafungin at 150 mg per day was administered as EAT or DET. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> In an intent-to-treat analysis of 413 patients, the incidence of probable/proven invasive fungal infection was 2.5% in the EAT group and 0.5% in the DET group, which fulfilled the predetermined criterion of noninferiority of the DET group (−2.0%; 90% CI, −4.0% to 0.1%). The survival rate was 98.0% versus 98.6% at day 42 and 96.4% versus 96.2% at day 84. The use of micafungin was significantly reduced in the DET group (60.2% v 32.5%; P < .001). </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> A novel strategy, DET, decreased the use and cost of antifungal agents without increasing invasive fungal infections and can be a reasonable alternative to empiric or preemptive antifungal therapy. </jats:p></jats:sec>
収録刊行物
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- Journal of Clinical Oncology
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Journal of Clinical Oncology 38 (8), 815-822, 2020-03-10
American Society of Clinical Oncology (ASCO)
