title: Role of management strategies in reducing mortality from invasive fungal disease in children with cancer or receiving hemopoietic stem cell transplant: a single center 30-year experience.
abstract: BACKGROUND
  In the last decades, several diagnostic and therapeutic strategies have been implemented for management of invasive fungal diseases (IFD) in patients with cancer or receiving allogeneic hemopoietic stem cell transplant. Few data are available on their impact on mortality in children.
  
  
  METHODS
  All IFD episodes diagnosed at tertiary care center during a 30-year period between 1983 and 2012 were analyzed for 90-day mortality and risk factors. Diagnoses were coded according to international (European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group) criteria. Four treatment eras (1983-1990, 1991-1999, 2000-2005 and 2006-2012) were defined according to availability of diagnostic technologies, new antifungal drugs and use of a diagnostic-driven approach without empiric antifungal therapy.
  
  
  RESULTS
  A total of 198 IFD were diagnosed in 191 patients; 71.2% were proven/probable infections; 39.9% were caused by yeasts and 31.3% by molds. Within 90 days from IFD diagnosis, 58 (30.4%) patients died for a 28.3% cumulative probability of death. A multivariable analysis showed that the highest risk of death was associated with alternative donor-hemopoietic stem cell transplant [hazard ratio (HR): 3.96] and mold etiology (HR: 1.34). The risk of death significantly decreased across the treatment eras, with almost a 3-fold reduced risk for patients diagnosed during the 2006-2012 period (HR: 0.24). Also if the variable year of diagnosis was considered as continuous, the hazard of death significantly decreased by 5% per year (HR: 0.95).
  
  
  CONCLUSIONS
  New management strategies resulted in a better prognosis of IFD in children with cancer or hemopoietic stem cell transplant. A diagnostic-driven approach was not associated with an increase in mortality.
authors.affiliation: From the *Infectious Diseases Unit; †Epidemiology and Biostatistics Unit; ‡Oncology Unit; §Hemopoietic Stem Cell Transplant Unit; ¶Hematology Unit; ‖Laboratory of Analysis; **Service of Radiology; ††Surgery Unit; and ‡‡Intensive Care Unit, "Istituto Giannina Gaslini", Genova, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Castagnola
authors.forename: Francesca
authors.initials: F
authors.lastname: Bagnasco
authors.forename: Loredana
authors.initials: L
authors.lastname: Amoroso
authors.forename: Ilaria
authors.initials: I
authors.lastname: Caviglia
authors.forename: Silvia
authors.initials: S
authors.lastname: Caruso
authors.forename: Maura
authors.initials: M
authors.lastname: Faraci
authors.forename: Michaela
authors.initials: M
authors.lastname: Calvillo
authors.forename: Cristina
authors.initials: C
authors.lastname: Moroni
authors.forename: Roberto
authors.initials: R
authors.lastname: Bandettini
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cangemi
authors.forename: Gian Michele
authors.initials: GM
authors.lastname: Magnano
authors.forename: Piero
authors.initials: P
authors.lastname: Buffa
authors.forename: Andrea
authors.initials: A
authors.lastname: Moscatelli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Haupt
mesh_terms: D000293:Adolescent; D000935:Antifungal Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000706:statistics & numerical data*; D006801:Humans; D007223:Infant; D008297:Male; D009181:Mycoses / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality*; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000935:Antifungal Agents