title: Antifungal prophylaxis in cancer patients after chemotherapy or hematopoietic stem-cell transplantation: systematic review and meta-analysis.
abstract: OBJECTIVE
  To evaluate the effect of antifungal prophylaxis on all-cause mortality as primary outcome, invasive fungal infections (IFIs), and adverse events. Many studies have evaluated the role of antifungal prophylaxis in cancer patients, with inconsistent conclusions.
  
  
  METHODS
  We performed a systematic review and meta-analysis of randomized, controlled trials comparing systemic antifungals with placebo, no intervention, or other antifungal agents for prophylaxis in cancer patients after chemotherapy. The Cochrane Library, MEDLINE, conference proceedings, and references were searched. Two reviewers independently appraised the quality of trials and extracted data.
  
  
  RESULTS
  Sixty-four trials met inclusion criteria. Antifungal prophylaxis decreased all-cause mortality significantly at end of follow-up compared with placebo, no treatment, or nonsystemic antifungals (relative risk [RR], 0.84; 95% CI, 0.74 to 0.95). In allogeneic hematopoietic stem-cell transplantation (HSCT) recipients, prophylaxis reduced all-cause mortality (RR, 0.62; 95% CI, 0.45 to 0.85), fungal-related mortality, and documented IFI. In acute leukemia patients, there was a significant reduction in fungal-related mortality and documented IFI, whereas the difference in mortality was only borderline significant (RR, 0.88; 95% CI, 0.74 to 1.06). Prophylaxis with itraconazole suspension reduced documented IFI when compared with fluconazole, with no difference in survival, and at the cost of more adverse events. On the basis of two studies, posaconazole prophylaxis reduced all-cause mortality (RR, 0.74; 95% CI, 0.56 to 0.98), fungal-related mortality, and IFI when compared with fluconazole.
  
  
  CONCLUSIONS
  Antifungal prophylaxis decreases all-cause mortality significantly in patients after chemotherapy. Antifungal prophylaxis should be administered to patients undergoing allogeneic HSCT, and should probably be administered to high-risk acute leukemia patients.
authors.affiliation: Department of Medicine E, Rabin Medical Center, Petah-Tiqva, Israel. Eyalr2@clalit.org.il
authors.forename: Eyal
authors.initials: E
authors.lastname: Robenshtok
authors.forename: Anat
authors.initials: A
authors.lastname: Gafter-Gvili
authors.forename: Elad
authors.initials: E
authors.lastname: Goldberg
authors.forename: Miriam
authors.initials: M
authors.lastname: Weinberger
authors.forename: Moshe
authors.initials: M
authors.lastname: Yeshurun
authors.forename: Leonard
authors.initials: L
authors.lastname: Leibovici
authors.forename: Mical
authors.initials: M
authors.lastname: Paul
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D002648:Child; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D009181:Mycoses / Q000209:etiology / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy / Q000382:microbiology* / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents