title: Earlier response assessment in invasive aspergillosis based on the kinetics of serum Aspergillus galactomannan: proposal for a new definition.
abstract: BACKGROUND
  Current criteria for assessing treatment response of invasive aspergillosis (IA) rely on nonspecific subjective parameters. We hypothesized that an Aspergillus-specific response definition based on the kinetics of serum Aspergillus galactomannan index (GMI) would provide earlier and more objective response assessment.
  
  
  METHODS
  We compared the 6-week European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) response criteria with GMI-based response among 115 cancer patients with IA. Success according to GMI required survival with repeatedly negative GMI for ≥2 weeks. Time to response and agreement between the 2 definitions were the study endpoints.
  
  
  RESULTS
  Success according to EORTC/MSG and GMI criteria was observed in 73 patients (63%) and 83 patients (72%), respectively. The GMI-based response was determined at a median of 21 days after treatment initiation (range, 15-41 days), 3 weeks before the EORTC/MSG time point, in 72 (87%) of 83 responders. Agreement between definitions was shown in all 32 nonresponders and in 73 of the 83 responders (91% overall), with an excellent κ correlation coefficient of 0.819. Among 10 patients with discordant response (EORTC/MSG failure, GMI success), 1 is alive without IA 3 years after diagnosis; for the other, aspergillosis could not be detected at autopsy. The presence of other life-threatening complications in the remaining 8 patients indicates that IA had resolved.
  
  
  CONCLUSIONS
  The Aspergillus-specific GMI-based criteria compare favorably to current response definitions for IA and significantly shorten time to response assessment. These criteria rely on a simple, reproducible, objective, and Aspergillus-specific test and should serve as the primary endpoint in trials of IA.
authors.affiliation: Department of Preventive Medicine and Myeloma Institute forResearch and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Nouér
authors.forename: Marcio
authors.initials: M
authors.lastname: Nucci
authors.forename: Naveen Sanath
authors.initials: NS
authors.lastname: Kumar
authors.forename: Monica
authors.initials: M
authors.lastname: Grazziutti
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: Elias
authors.initials: E
authors.lastname: Anaissie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008351:Mannans / Q000097:blood*; D008875:Middle Aged; D044967:Serum / Q000737:chemistry*; D013997:Time Factors
chemical_list: D008351:Mannans; C012990:galactomannan; D005690:Galactose