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

Eur J Haematol. 2016 Feb;96(2):175-80. doi: 10.1111/ejh.12565. Epub 2015 May 6.

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.

Keywords: acute myeloid leukaemia; fluconazole; invasive aspergillosis; invasive fungal disease; neutropenia; posaconazole; prophylaxis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cytarabine / therapeutic use
  • Daunorubicin / therapeutic use
  • Female
  • Fluconazole / therapeutic use*
  • Humans
  • Induction Chemotherapy / methods
  • Leukemia, Myeloid, Acute / complications
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Mycoses / etiology
  • Mycoses / mortality
  • Mycoses / prevention & control*
  • Myelodysplastic Syndromes / complications
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / pathology
  • Pre-Exposure Prophylaxis
  • Remission Induction
  • Retrospective Studies
  • Survival Analysis
  • Triazoles / therapeutic use*

Substances

  • Antifungal Agents
  • Triazoles
  • Cytarabine
  • posaconazole
  • Fluconazole
  • Daunorubicin