title: Correlation between Circulating Fungal Biomarkers and Clinical Outcome in Invasive Aspergillosis.
abstract: Objective means are needed to predict and assess clinical response in patients treated for invasive aspergillosis (IA). We examined whether early changes in serum galactomannan (GM) and/or β-D-glucan (BDG) can predict clinical outcomes. Patients with proven or probable IA were prospectively enrolled, and serial GM and BDG levels and GM optical density indices (GMI) were calculated twice weekly for 6 weeks following initiation of standard-of-care antifungal therapy. Changes in these biomarkers during the first 2 and 6 weeks of treatment were analyzed for associations with clinical response and survival at weeks 6 and 12. Among 47 patients with IA, 53.2% (25/47) and 65.9% (27/41) had clinical response by weeks 6 and 12, respectively. Changes in biomarkers during the first 2 weeks were associated with clinical response at 6 weeks (GMI, P = 0.03) and 12 weeks (GM+BDG composite, P = 0.05; GM, P = 0.04; GMI, P = 0.02). Changes in biomarkers during the first 6 weeks were also associated with clinical response at 6 weeks (GM, P = 0.05; GMI, P = 0.03) and 12 weeks (BDG+GM, P = 0.02; GM, P = 0.02; GMI, P = 0.01). Overall survival rates at 6 weeks and 12 weeks were 87.2% (41/47) and 79.1% (34/43), respectively. Decreasing biomarkers in the first 2 weeks were associated with survival at 6 weeks (BDG+GM, P = 0.03; BDG, P = 0.01; GM, P = 0.03) and at 12 weeks (BDG+GM, P = 0.01; BDG, P = 0.03; GM, P = 0.01; GMI, P = 0.007). Similar correlations occurred for biomarkers measured over 6 weeks. Patients with negative baseline GMI and/or persistently negative GMI during the first 2 weeks were more likely to have CR and survival. These results suggest that changes of biomarkers may be informative to predict and/or assess response to therapy and survival in patients treated for IA.
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, United States of America; Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, United States of America.
authors.forename: Dionysios
authors.initials: D
authors.lastname: Neofytos
authors.affiliation: Clinical Research, Merck & Co., Inc., Kenilworth, NJ, United States of America.
authors.forename: Radha
authors.initials: R
authors.lastname: Railkar
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL, United States of America.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Mullane
authors.affiliation: Division of Allergy and Infectious Diseases, Fred Hutchinson Center, Seattle, WA, United States of America.
authors.forename: David N
authors.initials: DN
authors.lastname: Fredricks
authors.affiliation: Division of Infectious Diseases, University of Texas M.D. Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Bruno
authors.initials: B
authors.lastname: Granwehr
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD, United States of America.
authors.forename: Kieren A
authors.initials: KA
authors.lastname: Marr
authors.affiliation: Roswell Park Cancer Institute, State University of New York, Buffalo, NY, United States of America.
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Almyroudis
authors.affiliation: Division of Infectious Diseases, University of Texas M.D. Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.affiliation: Department of Haematology, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.affiliation: Clinical Research, Merck & Co., Inc., Kenilworth, NJ, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Fox
authors.affiliation: Clinical Research, Merck & Co., Inc., Kenilworth, NJ, United States of America.
authors.forename: Cameron
authors.initials: C
authors.lastname: Douglas
authors.affiliation: Clinical Research, Merck & Co., Inc., Kenilworth, NJ, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Iannone
authors.affiliation: Clinical Research, Merck & Co., Inc., Kenilworth, NJ, United States of America.
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Kauh
authors.affiliation: Clinical Research, Merck & Co., Inc., Kenilworth, NJ, United States of America.
authors.forename: Norah
authors.initials: N
authors.lastname: Shire
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D001230:Aspergillus / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity; D015415:Biomarkers / Q000097:blood; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008351:Mannans / Q000097:blood*; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D047071:beta-Glucans / Q000097:blood*
chemical_list: D000935:Antifungal Agents; D015415:Biomarkers; D008351:Mannans; D047071:beta-Glucans; C012990:galactomannan; D005690:Galactose