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Blood, 15 March 2001, Vol. 97, No. 6, pp. 1604-1610
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Screening for circulating galactomannan as a noninvasive
diagnostic tool for invasive aspergillosis in prolonged neutropenic
patients and stem cell transplantation recipients: a
prospective validation
Johan Maertens,
Jan Verhaegen,
Katrien Lagrou,
Johan Van
Eldere, and
Marc Boogaerts
From the Departments of Hematology and Microbiology,
University Hospital Gasthuisberg, Leuven, Belgium.
The diagnosis of invasive aspergillosis (IA) in patients with
hematologic disorders is not straightforward; lack of sensitive and
specific noninvasive diagnostic tests remains a major obstacle for
establishing a precise diagnosis. In a series of 362 consecutive high-risk treatment episodes that were stratified according to the
probability of IA based on recently accepted case definition sets, the
potential for diagnosis of serial screening for circulating galactomannan (GM), a major aspergillar cell wall constituent was
validated. After incorporating postmortem findings to allow a more
accurate final analysis, this approach proved to have a sensitivity of
89.7% and a specificity of 98.1%. The positive and negative
predictive values equaled 87.5% and 98.4%, respectively. False-positive reactions occurred at a rate of 14%, although this figure might be overestimated due to diagnostic uncertainty. More or
less stringent criteria of estimation could highly influence sensitivity, which ranged from 100% to 42%; the impact on other test
statistics was far less dramatic. All proven cases of IA, including 23 cases confirmed after autopsy only, had been detected before death,
although serial sampling appeared to be necessary to maximize
detection. The excellent sensitivity and negative predictive value
makes this approach suitable for clinical decision making.
Unfortunately, given the species-specificity of the assay, some emerging non-Aspergillus mycoses were not detected. In
conclusion, serial screening for GM, complemented by
appropriate imaging techniques, is a sensitive and noninvasive tool for
the early diagnosis of IA in high-risk adult hematology patients.

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