title: Immunomodulation with interferon-gamma and colony-stimulating factors for refractory fungal infections in patients with leukemia.
abstract: BACKGROUND
  Invasive fungal infections (IFI) in immunocompromised patients are associated with significant morbidity and mortality, despite appropriate antifungal treatment and recovery from neutropenia. The outcome of these infections depends significantly on the overall state of immunosuppression, including mainly the phagocytic system (neutrophils and macrophages). Interferon-gamma (IFN-gamma), granulocyte-colony--stimulating factor (G-CSF) and granulocyte-macrophage-colony--stimulating factor (GM-CSF) are cytokines that enhance the activity of neutrophils and macrophages.
  
  
  METHODS
  The authors reported 4 patients with leukemia and refractory invasive candidiasis or trichosporonosis despite 1-13 months of appropriate antifungal treatment.
  
  
  RESULTS
  Cytokines were administered for 1.5-5 months without significant toxicity. For each patient, initiation of interferon-gamma plus a colony-stimulating factor resulted in a clinical response. The contribution of cytokines to control the fungal infection in these 4 patients was suggested by the strong inflammatory reaction observed in the 2 patients who had an immediate response (within 7 days of initiation of cytokine therapy) and by the good outcome in the 2 other patients in whom antifungal agents were discontinued at the start of cytokine therapy.
  
  
  CONCLUSIONS
  These data suggested a potential role for immunomodulation in patients with leukemia with refractory invasive fungal infections.
authors.affiliation: Division of Supportive Care, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Dignani
authors.forename: John H
authors.initials: JH
authors.lastname: Rex
authors.forename: Ka-Wah
authors.initials: KW
authors.lastname: Chan
authors.forename: Gordon
authors.initials: G
authors.lastname: Dow
authors.forename: Margarida
authors.initials: M
authors.lastname: deMagalhaes-Silverman
authors.forename: AnneMarie
authors.initials: A
authors.lastname: Maddox
authors.forename: Thomas
authors.initials: T
authors.lastname: Walsh
authors.forename: Elias
authors.initials: E
authors.lastname: Anaissie
mesh_terms: D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use; D025141:Drug Resistance, Fungal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects; D007371:Interferon-gamma / Q000627:therapeutic use*; D007938:Leukemia / Q000150:complications*; D008297:Male; D009181:Mycoses / Q000188:drug therapy*
chemical_list: D000935:Antifungal Agents; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma