title: A pilot study of targeted itraconazole prophylaxis in patients with graft-versus-host disease at high risk of invasive mould infections following allogeneic stem cell transplantation.
abstract: Patients with severe graft-versus-host disease (GVHD) requiring intensive immunosuppression are at high risk of invasive mould infections (IMI). Prophylaxis with an active, oral antifungal agents with reliable absorption in this context is desirable. A total of 44 patients at high risk of post-engraftment IMI received itraconazole solution 2.5 mg/kg b.d. as prophylaxis. Two of the first nine patients, in whom bioavailability was compromised due to significant vomiting and/or diarrhoea, died of probable or proven invasive aspergillus. None of the subsequent 35 patients, some of whom had severe gut GVHD and who received liposomal amphotericin B prophylaxis until itraconazole was reliably tolerated and absorbed, developed IMI. The overall incidence of IMI was substantially lower than in historical controls. Itraconazole was generally well tolerated, with five patients (11%) ceasing the drug due to intolerance or disturbed liver function. Targeted prophylaxis with oral or parenteral antifungal agents in high-risk allograft recipients appears to be effective in reducing the incidence of IMI.
authors.affiliation: Bone Marrow Transplant Service, Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Australia. andrew.grigg@mh.org.au
authors.forename: A P
authors.initials: AP
authors.lastname: Grigg
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: A W
authors.initials: AW
authors.lastname: Roberts
authors.forename: J
authors.initials: J
authors.lastname: Szer
authors.forename: M A
authors.initials: MA
authors.lastname: Slavin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001228:Aspergillosis / Q000188:drug therapy* / Q000401:mortality* / Q000517:prevention & control; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000382:microbiology; D006086:Graft vs Host Disease / Q000401:mortality*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D015994:Incidence; D017964:Itraconazole / Q000008:administration & dosage* / Q000009:adverse effects; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012307:Risk Factors; D014184:Transplantation, Homologous
chemical_list: D000935:Antifungal Agents; D008081:Liposomes; D017964:Itraconazole; D000666:Amphotericin B