Background: In allogeneic hematopoietic stem cell transplantation (HSCT) the risk of fungal infections is not only related to neutropenia, but mostly to GVHD prophylaxis/treatment and to the immunodeficiency state occurring after the allograft. The risk of fungal infections, especially of invasive aspergillosis is increased in patients transplanted from donors other than HLA-identical siblings. Methods: Open-label, multicenter (n=27), randomized pilot study in two groups of patients (A and B) . Patients belonging to both group A and B received short-term prophylaxis with ABLC 1 mg/kg/day until engraftment, unless a fungal infection was presumed or proven, or protracted neutropenia for 30 days was observed. Group B patients subsequently received ABLC 2.5 mg/kg/day two times per week until day 100 post-transplantation. The groups were comparable in terms of age, disease status, type of transplant and GVHD prophylaxis. End points of the study were: proportion of patients with absence of signs and symptoms of fungal infection during the 100 days following transplantation and safety. Results: 288 patients (group A: 145, group B: 143) were enrolled, 246 (85.4%) had an unrelated donor and 38 (13.2%) a mismatched family related donor. Out of 185 evaluable patients for assessment of fungal infections at day 100 post-transplantation, 17.5% of patients in group A and 13.3% in group B had either proven or presumed fungal infections (p=0.56). At the end of the study 142 patients were alive (49.3%). Survival was better for patients assigned to the group B as compared to those randomized to group A (log-rank test, 55.2% vs. 43.4%; p=0.045). Overall, 18.8% of patients died because of infection, 6.6% due to their underlying disease and 25.0% because of other transplant-related causes. The median time to death from date of first administration of ABLC was 181 days in group B and 134 days in group A (log-rank test, p=0.01). Treatment group A, GVHD+ and older age had a statistically significant effect on the probability of death. There was no statistically relevant difference in the incidence of severe acute GVHD or other infectious complications. The analysis of risk factors for fungal infection did not identify variables having a statistically significant effect. The safety profile was similar in both groups, but 33.1% of patients in group A and 21.7% in group B presented at least once a creatinine value above 220 mol/L (p=0.03). Conclusions: Long-term prophylaxis with ABLC after stem cell transplantation is superior to short-term prophylaxis. Both prophylaxis schedules were well tolerated.
Full conference title:
American Society of Hematology 45th Annual Meeting
- ASH 45th (2003)