title: Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study.
abstract: Acute graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). It has been proposed that tumor necrosis factor alpha (TNF-alpha) blockade with infliximab may be an effective treatment for severe (grades III-IV) GVHD. We determined if infliximab use in this high-risk population was associated with an additional increased risk of non-Candida invasive fungal infections (IFIs). Records of the 2000-2001 HSCT cohort at our institution were reviewed. Fifty-three (20%) of 264 evaluable patients developed severe GVHD and 11 of these 53 (21%) received infliximab for treatment. Proven or probable IFI was documented in 10 (19%) of 53 patients with severe GVHD (incidence rate of 0.99 cases/1000 GVHD patient-days). When stratified by infliximab use, 5 of 11 infliximab recipients developed an IFI (6.78 cases/1000 GVHD patient-days), compared with 5 of 42 IFI cases among nonrecipients (0.53 cases/1000 GVHD patient-days). In a time-dependent Cox regression model among patients with severe GVHD, the adjusted IFI hazard ratio of infliximab exposure was 13.6 (P =.004; 95% CI, 2.29-80.2). We conclude that infliximab administration is associated with a significantly increased risk of non-Candida IFI in HSCT recipients with severe GVHD disease. Pre-emptive systemic antifungal therapy against molds should be considered in patients who develop severe GVHD after HSCT if infliximab is used.
authors.affiliation: Division of Infectious Diseases and Hematopoietic Stem-Cell Transpalntation Service, Brigham and Women's Hospital and Dana-Farber Cancer Instiute, Harvard Medical School, Boston, MA 02115, USA. fmarty@partners.org
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Marty
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Fahey
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015331:Cohort Studies; D003879:Dermatologic Agents / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009181:Mycoses / Q000209:etiology*; D012306:Risk; D012307:Risk Factors; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects*
chemical_list: D000911:Antibodies, Monoclonal; D003879:Dermatologic Agents; D000069285:Infliximab