Empiric versus pre-emptive antifungal strategy in high-risk neutropenic patients on fluconazole prophylaxis: a randomized trial of the European organization for Research and Treatment of cancer (EORTC 65091).
Maertens, Johan; Lodewyck, Tom; Peter Donnelly, Jet al.
2023 • In Clinical Infectious Diseases, 76 (4), p. 674-682
[en] BACKGROUND: Empiric antifungal therapy is considered the standard-of-care for high-risk neutropenic patients with persistent fever. The impact of a pre-emptive, diagnostic-driven approach based on galactomannan (GM) screening and chest CT-scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. METHODS: Patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (Arm A) or pre-emptively (Arm B). All patients received fluconazole 400 mg daily as prophylaxis. The primary endpoint of this non-inferiority study was overall survival (OS) 42 days after randomization. RESULTS: Of 556 patients recruited, 549 were eligible: 275 in Arm A, 274 in Arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy and 93% of them were in first induction phase. At day 42, the OS was not inferior in Arm B (96.7%; 95% confidence interval (CI), 93.8 - 98.3%) when compared to Arm A (93.1%; 95% CI, 89.3 - 95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95%CI, 4.5-10.8%) in Arm B versus 6.6% (95%CI, 3.6-9.5%) in Arm A, respectively. The rate of patients receiving caspofungin was significantly lower in Arm B (27%) than in Arm A (63%) (p < 0.001). CONCLUSIONS: The pre-emptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs.
Disciplines :
Immunology & infectious disease
Author, co-author :
Maertens, Johan; University Hospitals Leuven, Leuven, BE.
Lodewyck, Tom; AZ St Jan, Brugge, BE.
Peter Donnelly, J; Radboud UMC, Nijmegen, NL.
Chantepie, Sylvain; Caen University Hospital, Caen, FR.
Robin, Christine; Centre Hospitalier Universitaire Henri Mondor, Créteil, FR.
Blijlevens, Nicole; Radboud UMC, Nijmegen, NL.
Turlure, Pascal; Centre Hospitalier Universitaire Limoges, Limoges, FR.
Selleslag, Dominik; AZ St Jan, Brugge, BE.
Baron, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie clinique
Aoun, Mickael; Institut Jules Bordet, Brussels, BE.
Heinz, Werner J; Caritas Hospital, Bad Mergentheim, DE.
Bertz, Hartmut; Faculty of Medicine and Medical Centre, University of Freiburg, Freiburg, DE.
Ráčil, Zdeněk; Masaryk University Brno and Institute of Hematology and Blood Transfusion,
Vandercam, Bernard; Cliniques Universitaires St. Luc, Brussels, BE.
Drgona, Lubos; Comenius University and National Cancer Institute, Bratislava, SK.
Coiteux, Valerie; Centre Hospitalier Régional Universitaire Lille, Lille, FR.
Llorente, Cristina Castilla; Gustave Roussy Cancer campus, Villejuif, FR.
Empiric versus pre-emptive antifungal strategy in high-risk neutropenic patients on fluconazole prophylaxis: a randomized trial of the European organization for Research and Treatment of cancer (EORTC 65091).
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