title: A comprehensive diagnostic approach using galactomannan, targeted β-d-glucan, baseline computerized tomography and biopsy yields a significant burden of invasive fungal disease in at risk haematology patients.
abstract: Invasive fungal disease (IFD) is difficult to diagnose. We investigated the incidence of IFD and risk factors using the revised European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG) definitions. Patients (N = 203) undergoing intensive therapy with expected neutropenia ≥10 d were recruited prospectively and followed for a median (range) of 556 (12-730) d. Baseline chest computerized tomography (CT) was performed pre-therapy. Twice-weekly surveillance with galactomannan (GM) was combined with targeted β-d-glucan (BDG) testing on patients with possible IFD or who were GM-positive. Tissue diagnosis was obtained whenever possible. The cumulative incidence of proven/probable IFD among the 202 evaluable cases after 2 years follow-up was 21%, including 14 proven and 30 probable IFDs. Using either GM or BDG as the sole biomarker (plus host and clinical evidence) the apparent overall incidence of proven/probable IFD was 11% and 16%, respectively. Combined GM/BDG detected all biopsy-proven mould IFD. Baseline CT abnormalities were found in 76/202 (38%) patients. Baseline CT abnormalities and Karnofsky score <90, monocytopenia >10 d and bacteraemia were independent risk factors associated with greater than twofold increased IFD risk. This combined diagnostic approach identified a high incidence of IFD and important risk factors in this cohort.
authors.affiliation: Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, UK.
authors.forename: M Mansour
authors.initials: MM
authors.lastname: Ceesay
authors.forename: Sujal R
authors.initials: SR
authors.lastname: Desai
authors.forename: Lisa
authors.initials: L
authors.lastname: Berry
authors.forename: Joanne
authors.initials: J
authors.lastname: Cleverley
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Kibbler
authors.forename: Sabine
authors.initials: S
authors.lastname: Pomplun
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Nicholson
authors.forename: Abdel
authors.initials: A
authors.lastname: Douiri
authors.forename: Jim
authors.initials: J
authors.lastname: Wade
authors.forename: Melvyn
authors.initials: M
authors.lastname: Smith
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagliuca
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D005936:Glucans / Q000032:analysis*; D006402:Hematologic Diseases / Q000382:microbiology*; D006801:Humans; D008297:Male; D008351:Mannans / Q000032:analysis*; D008875:Middle Aged; D009181:Mycoses / Q000097:blood / Q000175:diagnosis*; D012307:Risk Factors; D014057:Tomography, X-Ray Computed / Q000379:methods; D055815:Young Adult
chemical_list: D005936:Glucans; D008351:Mannans; C012990:galactomannan; D005690:Galactose
keywords: galactomannan; incidence; invasive fungal disease; risk factors; β-d-glucan