A reduced dose of fluconazole as primary antifungal prophylaxis is not associated with increased risk of invasive fungal infections after allogeneic stem cell transplantation from a HLA identical sibling

Transpl Infect Dis. 2018 Aug;20(4):e12906. doi: 10.1111/tid.12906. Epub 2018 May 16.

Abstract

Background: Invasive fungal infections (IFI) represent a common side effect of allogeneic hematopoietic stem cell transplant (allo-SCT), resulting in increased non relapse mortality (NRM) and reduced overall survival (OS) rates. Seventy-five days of Fluconazole 400 mg/d represents the standard primary antifungal prophylaxis (PAP) after allo-SCT, especially for low-risk transplants. However, the ideal dosage of fluconazole has never been tested.

Methods: Here, we report the experience of our institution on 113 consecutive patients receiving an allo-SCT from a HLA identical sibling between 1999 and 2015, where PAP consisted of fluconazole 100 mg/d only during the pre-engraftment phase. At the time of transplant, all patients were considered at low-risk for mold infection according to ECIL-5 guidelines.

Results: Cumulative incidence of possible-probable-proven IFI was 11.7%, while proven-probable (PP-IFI) occurred in 5.5% of patients by day 100 post transplant. Of note, only 1 patient developed invasive Candidiasis due to a non-albicans strain and stool-screening tests were negative for colonization by Candida albicans species. The incidence of 1-year acute and 2-year chronic graft-versus-host-disease (GVHD) was 30% and 45%, respectively. Three-year OS and 1-year NRM were 53% and 11.3%, respectively.

Conclusion: In summary, fungal prophylaxis with fluconazole 100 mg/d results in very low incidence of PP-IFI, GVHD and NRM in low-risk allo-SCT.

Keywords: allogeneic stem cell transplant; fluconazole; primary antifungal prophylaxis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibiotic Prophylaxis / methods*
  • Antifungal Agents / administration & dosage*
  • Dose-Response Relationship, Drug
  • Female
  • Fluconazole / administration & dosage*
  • Follow-Up Studies
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • HLA Antigens / immunology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Incidence
  • Invasive Fungal Infections / epidemiology
  • Invasive Fungal Infections / microbiology
  • Invasive Fungal Infections / prevention & control*
  • Living Donors
  • Lymphoma / immunology
  • Lymphoma / mortality
  • Lymphoma / surgery
  • Male
  • Middle Aged
  • Retrospective Studies
  • Siblings
  • Survival Rate
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / methods
  • Treatment Outcome
  • Young Adult

Substances

  • Antifungal Agents
  • HLA Antigens
  • Fluconazole