Background: Invasive fungal infections (IFI), especially invasive aspergillosis (IA) are an important cause of morbidity and mortality after allogeneic hematopoietic stem-cell transplantation (Allo-HSCT). Therefore, the prevention of IFI up-front has become the major goal in patient care in these high-risk patient populations. Posaconazole seems to be a valid alternative to old triazoles as it offers both an extended-spectrum activity and an acceptable toxicity profile. In this retrospective, single-center study we evaluated the efficacy of posaconazole for the prevention of IA in patients with acute leukemia who underwent Allo-HSCT between May 2010 and October 2012.
Methods: A total of 62 patients, 40 with acute myeloid leukemia (AML), and 22 with acute lymphoblastic leukemia (ALL) were analyzed. Primary prophylaxis with posaconazole was commenced on day 0 with a dose 400 mg/bid. Failure of prophylaxis was characterized as progressive clinical or radiologic parameters compared with baseline, and as switch to another systemic antifungal agent. The observation period lasted from start of prophylaxis until to the day +100.
Results: Posaconazole prophylaxis failed in 20 patients (32.2%). While possible IA was observed in 5 patients (8%), no proven/probable IA was documented. The potential risk factors for failure of prophylaxis were evaluated by multivariate analyses as well as univariate analysis (Table I). The multivariate analysis showed that the following factors were associated with failure of prophylaxis: remission status of disease up-front Allo-HSCT and type of conditioning regimen. Patients with active disease up-front Allo-HSCT or usage of cyclophosphamide + busulfex as a conditioning regimen were more likely to have failure of posaconazole prophylaxis. In addition, overall mortality (first 100 days) was much higher in the patients having prophylaxis failure (20% vs 0%, p=0.018).
Conclusions:Posaconazole was effective oral antifungal prophylaxis in acute leukemia patients who underwent Allo-HSCT. However, having an active disease up-front of the HSCT and usage of cyclophosphamide + busulfex as a conditioning regimen were associated with failure of posaconazole prophylaxis. The physicians must identify IA cases as soon as possible in order to guarantee early and adequate treatment to these high-risk patient subpopulations
Full conference title:
- EBMT 39th (2013)