Background Fungal infections remain the leading cause of death from infection in hematopoietic stem cell transplant (HSCT) recipients. The prophylatic efficacy of antifungal agents has been limited by toxicities and narrow spectrum coverage. We performed a prospective randomised trial to compare the efficacy of itraconazole and low dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT, and to determine their impact on overall survival at day 100. Methods Patients undergoing allogeneic or autologous HSCT were randomised to receive itraconzole oral solution 200mg/day or amphotericin B 0.2 mg/kg/day i.v. beginning 1 day prior to commencement of conditioning regimen and continued until engraftment, suspected drug-associated toxicity, or systemic fungal infection occured. Therapeutic doses of systemic antifungal agents were started for breakthrough fungal infections defined as proven, probable or possible, according to standardised EORTC/MSG criteria. Results There was no statistically significant difference between the two treatment arms (n= 161; 89 itraconazole, 72 AmB) for any demographic variables, duration of neutropenia, steroid therapy, fever and antifungal prophylaxis. There was also no statistically significant difference between the 2 arms in terms of discontinuation of prophylaxis due to suspected or proven fungal infections (itraconazole 29.2% Vs AmB 37.6, p=0.27). Although discontinuation of prophylaxis due to toxicities was similar (itraconazole 20% Vs AmB 14%, p=0.40), gastrointestinal intolerance or liver toxicity leading to discontinuation of prophylaxis was only seen among itraconazole recipients (itraconazole 13% Vs AmB 0%, p=0.002, and itraconazole 6.7% Vs AmB 0%, p=0.025). Conversely, renal dysfunction leading to discontinuation of prophylaxis was only seen in AmB recipients (itraconazole 0% Vs AmB 12.5%, p=0.01).There was a similar incidence of proven (itraconazole 4.5% Vs AmB 2.8%, p=0.57), probable (itraconazole 2.2% Vs AmB 1.4%, p=0.69) and possible (itraconazole 3.4% Vs AmB 8.3%, p=0.31) fungal infections. Both agents provided similar protection against invasive mould and yeast infections (p>0.05). Death was attributable to fungal infections in 3 (3.4%) itraconazole recipients and 4 (5.6%) AmB recipients (p=0.5). Kaplan Meier analysis of the survival at 100 days of transplant was similar between the treatment arms (itraconazole 89% Vs AmB 84%, p=0.33). Conclusions Itraconazole and low dose AmB confer equal protection against invasive fungal infections among HSCT recipients.
Full conference title:
American Society of Hematology 45th Annual Meeting
- ASH 45th (2003)