title: Tolerability and outcome of once weekly liposomal amphotericin B for the prevention of invasive fungal infections in hematopoietic stem cell transplant patients with graft-versus-host disease.
abstract: BACKGROUND
  Invasive fungal infections remain problematic in immunosuppressed allogeneic stem cell transplant recipients and the use of corticosteroids for the treatment of graft-versus-host-disease can increase the risk threefold. Although antifungal prophylaxis has been shown to decrease the incidence of infection, the optimal antifungal prophylactic regimen in this patient population has yet to be identified.Since early diagnosis of fungal infections might not be possible and the treatment of established fungal infections might be difficult and associated with high infection-related mortality, prevention has become an important strategy in reducing overall morbidity and mortality. While triazoles are the preferred agents, some patients are unable to tolerate them and an alternative drug is warranted.
  
  
  OBJECTIVE
  To assess the tolerability of once weekly liposomal amphotericin B as a prophylactic strategy in patients undergoing stem cell transplantation by evaluating any adverse events leading to its discontinuation. In terms of efficacy, to also compare the outcome and incidence of invasive fungal infections in patients who received amphotericin B, triazoles, and echinocandins.
  
  
  RESULTS
  A total of 101 allogeneic transplant recipients receiving corticosteroids for the treatment of graft-versus-host-disease and antifungal prophylaxis were evaluated from August 2009 to September 2012. Liposomal amphotericin B 3 mg/kg intravenous once weekly was found to be well tolerated. The incidence of invasive fungal infections was 19%, 17%, and 7% in the liposomal amphotericin B, echinocandin, and triazole groups, respectively. Two deaths occurred in the liposomal amphotericin B group and one death occurred in the echinocandin group. None of the deaths were fungal infection related.
  
  
  CONCLUSIONS
  Antifungal prophylaxis with liposomal amphotericin B was well tolerated, but the incidence of invasive fungal infections in patients receiving liposomal amphotericin B was higher than other antifungal agents in this study. The optimal dose and schedule of liposomal amphotericin B for antifungal prophylaxis in this patient population are still not known and considering its broad spectrum activity, prospective trials in comparison to triazoles are warranted.
authors.affiliation: Department of Pharmacy, The University of Kansas Hospital, Kansas City, KS, USA htran1@kumc.edu.
authors.forename: Huong
authors.initials: H
authors.lastname: Luu Tran
authors.affiliation: Department of Pharmacy, The University of Kansas Hospital, Kansas City, KS, USA.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Mahmoudjafari
authors.affiliation: Department of Pharmacy, The University of Kansas Hospital, Kansas City, KS, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Rockey
authors.affiliation: School of Pharmacy, University of Kansas, Lawrence, KS, USA.
authors.forename: Dave
authors.initials: D
authors.lastname: Henry
authors.affiliation: School of Pharmacy, University of Kansas, Lawrence, KS, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Grauer
authors.affiliation: Department of Blood and Marrow Transplant, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Aljitawi
authors.affiliation: Department of Blood and Marrow Transplant, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Abhyankar
authors.affiliation: Department of Blood and Marrow Transplant, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Ganguly
authors.affiliation: Department of Blood and Marrow Transplant, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Blood and Marrow Transplant, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: McGuirk
mesh_terms: D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D000072742:Invasive Fungal Infections / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B
keywords: Liposomal amphotericin B; corticosteroids; graft-versus-host-disease; hematopoietic stem cell transplant; invasive fungal infections; prophylaxis