A comprehensive diagnostic approach using galactomannan, targeted b-D-glucan, baseline computerized tomography and biopsy yields a significant burden of invasive fungal disease in at risk haematology patients

Author: 

M. Mansour Ceesay,1 Sujal R. Desai,2 Lisa Berry,3 Joanne Cleverley,4 Christopher C. Kibbler,5 Sabine Pomplun,6 Andrew G. Nicholson,7 Abdel Douiri,8 Jim Wade,9 Melvyn Smith,3 Ghulam J. Mufti1 and Antonio Pagliuca1

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 b-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.
Keywords: invasive fungal disease, galactomannan, b-D-glucan, incidence,
risk factors.