title: Voriconazole exposure and the risk of cutaneous squamous cell carcinoma in allogeneic hematopoietic stem cell transplant patients.
abstract: BACKGROUND
  Voriconazole is a commonly used antifungal medication in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. In solid organ transplantation, voriconazole use has been associated with the development of cutaneous squamous cell carcinoma (SCC). We sought to determine if voriconazole use was associated with SCC in patients undergoing allo-HSCT.
  
  
  METHODS
  We retrospectively reviewed consecutive adult patients who underwent allo-HSCT at Mayo Clinic from January 2007 through July 2012. Multivariable Cox models were created to assess the relationship of SCC with two time-dependent voriconazole exposure variables: (i) history of voriconazole exposure (yes/no), and (ii) cumulative days of voriconazole use.
  
  
  RESULTS
  In our cohort of 381 allo-HSCT patients, SCC developed in 26 of 312 patients exposed to voriconazole (25 post-voriconazole) and in 1 of 69 patients who received alternative antifungal agent(s). Cumulative incidence of SCC was estimated to be 19% at 5 years post allo-transplant. Cumulative days of voriconazole use was found to be a risk factor for SCC, and this relationship persisted in a multivariable model using previously identified risk factors as covariates (hazard ratio 1.859 for each 180 days of use, P < 0.001).
  
  
  CONCLUSIONS
  This is the first study, to our knowledge, to identify cumulative days of voriconazole use as a risk factor for SCC development following allo-HSCT, and may help guide appropriate antifungal use in this patient population.
authors: Department of Pharmacy, Mayo Clinic, Rochester, Minnesota, USA.
authors: D J
authors: DJ
authors: Wojenski
authors: G T
authors: GT
authors: Bartoo
authors: J A
authors: JA
authors: Merten
authors: R A
authors: RA
authors: Dierkhising
authors: M R
authors: MR
authors: Barajas
authors: R A
authors: RA
authors: El-Azhary
authors: J W
authors: JW
authors: Wilson
authors: M F
authors: MF
authors: Plevak
authors: W J
authors: WJ
authors: Hogan
authors: M R
authors: MR
authors: Litzow
authors: M M
authors: MM
authors: Patnaik
authors: R C
authors: RC
authors: Wolf
authors: S K
authors: SK
authors: Hashmi
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000276:immunology / Q000517:prevention & control*; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000276:immunology; D014184:Transplantation, Homologous; D065819:Voriconazole / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D065819:Voriconazole
keywords: cutaneous squamous cell carcinoma; hematopoietic stem cell transplantation; immunocompromised host; triazole adverse effects; voriconazole