Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation

The diagnosis of invasive aspergillosis (IA) in patients with hematologic d isorders is not straightforward; lack of sensitive and specific noninvasive diagnostic tests remains a major obstacle for establishing a precise diagn osis. In a series of 362 consecutive high-risk treatment episodes that were stratified according to the probability of IA based on recently accepted c ase definition sets, the potential for diagnosis of serial screening for ci rculating galactomannan (GM), a major aspergillar cell wall constituent was validated. After incorporating postmortem findings to allow a more accurat e 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% end 98.4%, respectively, False-positive reactions occurred at a rate of 14%, although this figure might be overestimated due to diagnostic uncer tainty. More or less stringent criteria of estimation could highly influenc e sensitivity, which ranged from 100% to 42%; the impact on other test stat istics was far less dramatic. All proven cases of IA, including 23 cases co nfirmed after autopsy only, had been detected before death, although serial sampling appeared to be necessary to maximize detection. The excellent sen sitivity and negative predictive value makes this approach suitable for cli nical decision making. Unfortunately, given the species-specificity of the assay, some emerging non-Aspergillus mycoses were not detected. In conclusi on, 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. (Blood. 2001;97:1604-1610) (C) 2001 by The American Society of Hematology.