Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients.
The recent advent of an improved commercial serum enzyme-linked immunosorbent assay (ELISA) for the detection of circulating galactomannan (GM), a major constituent of Aspergillus cell walls, has contributed to the diagnosis of invasive aspergillosis (IA) in many haematology and transplant centres. However, the optimal threshold for positivity remains a matter of debate. We prospectively evaluated the impact of lowering the cut-off in 124 neutropenic episodes with a high pretest probability for IA. Two new cut-off points, lower than previously accepted, are proposed: (a) a 'static' cut-off at 0.8 and (b) a 'dynamic' cut-off at 0.5. A single assay with an optical density (OD) index > or = 0.8 warrants the initiation of anti-Aspergillus therapy. A further lowering of the 'static' threshold seems not clinically feasible given the drop in positive predictive value (PPV). However, the demonstration of at least two sequential sera with an OD > or = 0.5 ('dynamic' threshold) increased the specificity and the PPV to 98.6% and the efficiency to 98%. Applying both cut-offs to a subgroup of 21 'possible' fungal infections further identified and upgraded six cases of IA. However, the clinical benefit of lower cut-offs (particularly for earlier diagnosis) depends upon the kinetics of antigenaemia and the intensity of serum sampling.
Maertens
Johan
J
Department of Haematology, University Hospital Gasthuisberg, Leuven, Belgium. johan.maertens@uz.kuleuven.ac.be
Theunissen
Koen
K
Verbeken
Eric
E
Lagrou
Katrien
K
Verhaegen
Jan
J
Boogaerts
Marc
M
Eldere
Johan Van
JV
D000293:Adolescent; D000328:Adult; D000368:Aged; D001228:Aspergillosis / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005240:Feasibility Studies; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008351:Mannans / Q000097:blood*; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications*; D009894:Opportunistic Infections / Q000175:diagnosis*; D011446:Prospective Studies; D012680:Sensitivity and Specificity
D015415:Biomarkers; D008351:Mannans; C012990:galactomannan; D005690:Galactose