title: Risk factors for post-engraftment invasive aspergillosis in allogeneic stem cell transplantation.
abstract: The majority of invasive aspergillosis (IA) in allogeneic stem cell transplantation (SCT) occurs during the post-engraftment period. We used Cox proportional hazards regression to evaluate post-engraftment IA risk in a cohort of 217 allogeneic SCT recipients from 1991 to 1998. The aim was to quantify the effects of dose-intensity and duration of corticosteroids and other risk factors. Median duration of follow-up was 330 days. There were 19 cases of IA (overall 8.8%) with 14 post-engraftment infections. In the final model, the risk of IA was greatest within 2 weeks of high-dose corticosteroids (HR 8.5, P=0.003), with risk extending to 4 weeks with doses of 0.25-1 mg/kg/day (HR 3.1, P=0.08). Ganciclovir was associated with greatest risk (HR 13.6). Grade 3 or 4 acute GVHD (HR 5.7) and secondary neutropenia (HR=1.3) were also additive risks. In the univariate analysis, corticosteroid doses of 0.25-1.0 mg/kg/day for any duration between 2 and 10 weeks demonstrated prolonged risk for IA. Moderate doses of corticosteroids can confer an increased risk for IA for extended periods which is almost as marked as that conferred by higher doses. Knowledge of these risks may facilitate the development of targeted surveillance and prophylaxis strategies for prevention of IA.
authors.affiliation: Victorian Infectious Diseases Service and National Health and Medical Research Council Centre of Clinical Research Excellence in Infectious Diseases, Royal Melbourne Hospital, Melbourne, Australia. Karin.Thursky@mh.org.au
authors.forename: K
authors.initials: K
authors.lastname: Thursky
authors.forename: G
authors.initials: G
authors.lastname: Byrnes
authors.forename: A
authors.initials: A
authors.lastname: Grigg
authors.forename: J
authors.initials: J
authors.lastname: Szer
authors.forename: M
authors.initials: M
authors.lastname: Slavin
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use / Q000633:toxicity; D000328:Adult; D000368:Aged; D001228:Aspergillosis / Q000139:chemically induced / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use / Q000633:toxicity; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000150:complications; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous
chemical_list: D000305:Adrenal Cortex Hormones; D015774:Ganciclovir