title: Decreased invasive fungal disease but no impact on overall survival by posaconazole compared to fluconazole prophylaxis: a retrospective cohort study in patients receiving induction therapy for acute myeloid leukaemia/myelodysplastic syndromes.
abstract: OBJECTIVE
  Posaconazole prophylaxis during induction chemotherapy for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) has been shown to significantly decrease the incidence of invasive fungal disease (IFD) and increase overall survival in a trial setting, but only small real-life studies have been published.
  
  
  METHODS
  This was a retrospective cohort study including consecutive patients with AML/MDS treated with intensive induction chemotherapy; 176 patients received fluconazole prophylaxis 2008-2011 and 107 patients received posaconazole prophylaxis 2011-2013. Only proven and probable IFD according to the revised EORTC/MSG criteria were included in the analysis.
  
  
  RESULTS
  The two cohorts were well matched without significant differences in patient characteristics. At day 100, patients receiving posaconazole had a significantly lower incidence of total IFD (0.9% vs. 10.8%, P < 0.01), invasive aspergillosis (0% vs. 5.7%, P = 0.02) and invasive candidiasis (0% vs. 4.0%, P < 0.05). There was no significant difference in overall survival, neither at day 100 (87% in the posaconazole group vs. 85% in the fluconazole group) nor at end of follow-up (78% vs. 77%).
  
  
  CONCLUSIONS
  Posaconazole prophylaxis decreased the incidence of IFD but did not improve short-term overall survival. Improved treatment efficacy of manifest IFD is likely to explain the lack of survival benefit.
authors.affiliation: Department of Medicine Solna, Division of Hematology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Torsten
authors.initials: T
authors.lastname: Dahlén
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Kalin
authors.affiliation: Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Cederlund
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Nordlander
authors.affiliation: Department of Medicine Solna, Division of Hematology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.affiliation: Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Blennow
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D065129:Pre-Exposure Prophylaxis; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; D003561:Cytarabine; C101425:posaconazole; D015725:Fluconazole; D003630:Daunorubicin
keywords: acute myeloid leukaemia; fluconazole; invasive aspergillosis; invasive fungal disease; neutropenia; posaconazole; prophylaxis