title: Serum galactomannan versus a combination of galactomannan and polymerase chain reaction-based Aspergillus DNA detection for early therapy of invasive aspergillosis in high-risk hematological patients: a randomized controlled trial.
abstract: BACKGROUND
  The benefit of the combination of serum galactomannan (GM) assay and polymerase chain reaction (PCR)-based detection of serum Aspergillus DNA for the early diagnosis and therapy of invasive aspergillosis (IA) in high-risk hematological patients remains unclear.
  
  
  METHODS
  We performed an open-label, controlled, parallel-group randomized trial in 13 Spanish centers. Adult patients with acute myeloid leukemia and myelodysplastic syndrome on induction therapy or allogeneic hematopoietic stem cell transplant recipients were randomized (1:1 ratio) to 1 of 2 arms: "GM-PCR group" (the results of serial serum GM and PCR assays were provided to treating physicians) and "GM group" (only the results of serum GM were informed). Positivity in either assay prompted thoracic computed tomography scan and initiation of antifungal therapy. No antimold prophylaxis was permitted.
  
  
  RESULTS
  Overall, 219 patients underwent randomization (105 in the GM-PCR group and 114 in the GM group). The cumulative incidence of "proven" or "probable" IA (primary study outcome) was lower in the GM-PCR group (4.2% vs 13.1%; odds ratio, 0.29 [95% confidence interval, .09-.91]). The median interval from the start of monitoring to the diagnosis of IA was lower in the GM-PCR group (13 vs 20 days; P = .022), as well as the use of empirical antifungal therapy (16.7% vs 29.0%; P = .038). Patients in the GM-PCR group had higher proven or probable IA-free survival (P = .027).
  
  
  CONCLUSIONS
  A combined monitoring strategy based on serum GM and Aspergillus DNA was associated with an earlier diagnosis and a lower incidence of IA in high-risk hematological patients. Clinical Trials Registration. NCT01742026.
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid.
authors.forename: José María
authors.initials: JM
authors.lastname: Aguado
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Vázquez
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid.
authors.forename: Mario
authors.initials: M
authors.lastname: Fernández-Ruiz
authors.affiliation: Department of Hematology, Fundación Jiménez Díaz, Madrid.
authors.forename: Teresa
authors.initials: T
authors.lastname: Villaescusa
authors.affiliation: Department of Infectious Diseases.
authors.forename: Isabel
authors.initials: I
authors.lastname: Ruiz-Camps
authors.affiliation: Department of Hematology, Hospital Universitari Vall d'Hebron, Barcelona.
authors.forename: Pere
authors.initials: P
authors.lastname: Barba
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid.
authors.forename: Jose T
authors.initials: JT
authors.lastname: Silva
authors.affiliation: Department of Clinical Hematology, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Batlle
authors.affiliation: Department of Hematology and Medical Oncology, Hospital Clínico Universitario-INCLIVA, Valencia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Solano
authors.affiliation: Department of Hematology, Institut Català d'Oncologia, Hospital Josep Trueta, Girona.
authors.forename: David
authors.initials: D
authors.lastname: Gallardo
authors.affiliation: Department of Hematology, Hospital Universitario Morales Meseguer, Murcia.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Heras
authors.affiliation: Department of Hematology, Hospital Clínico Universitario San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid.
authors.forename: Marta
authors.initials: M
authors.lastname: Polo
authors.affiliation: Department of Hematology, Complexo Hospitalario Universitario A Coruña.
authors.forename: Rosario
authors.initials: R
authors.lastname: Varela
authors.affiliation: Department of Hematology, Hospital Universitario Central de Asturias, Oviedo.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vallejo
authors.affiliation: Department of Hematology, Hospital Clínico Universitario de Zaragoza.
authors.forename: Teresa
authors.initials: T
authors.lastname: Olave
authors.affiliation: Department of Hematology, Hospital Universitario Ramón y Cajal, Madrid.
authors.forename: Javier
authors.initials: J
authors.lastname: López-Jiménez
authors.affiliation: Department of Hematology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rovira
authors.affiliation: Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla.
authors.forename: Rocío
authors.initials: R
authors.lastname: Parody
authors.affiliation: Department of Mycology, Spanish National Center for Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cuenca-Estrella
mesh_terms: D000328:Adult; D000368:Aged; D001228:Aspergillosis / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics / Q000628:therapy; D001230:Aspergillus / Q000235:genetics; D004271:DNA, Fungal / Q000097:blood; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications*; D008297:Male; D008351:Mannans / Q000097:blood*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications*; D060888:Real-Time Polymerase Chain Reaction; D055502:Secondary Prevention
chemical_list: D004271:DNA, Fungal; D008351:Mannans; C012990:galactomannan; D005690:Galactose
keywords: PCR; clinical trial; galactomannan; invasive aspergillosis; monitoring