Long-term follow up of invasive aspergillosis in allogeneic stem cell transplantation recipients and leukemia patients: Differences in risk factors and outcomes

Antifungal prophylaxis (AP) has dramatically changed the epidemiology of invasive aspergillosis (IA). To better understand the differences in terms of clinical significance of IA between allogeneic stem cell transplantation (allo-SCT) recipients and patients treated for leukemia, we report a single-center study of 735 unselected consecutive patients treated between 2000 and 2004, before the era of systematic AP. Probable or confirmed IA were observed in 29 patients (2008 EORTC/MSG criteria), including 7/235 undergoing allo-SCT (5.2%), 19/380 treated for acute leukemia (5.0%), 1/116 for chronic lymphocytic leukemia (0.9%) and 2/104 for myelodysplastic syndrome (1.9%). In allo-SCT recipients, IA occurred later than in leukemia patients, after the neutropenic period. The median time between the last treatment and the diagnosis of IA was 231 days (range, 68-341) in allo-SCT recipients and 17 days (6-57) in leukemia patients (P<0.001). Importantly, the 7 cases of IA after allo- SCT occurred only in patients treated with corticosteroids for graft-versus-host disease (GVHD). Mortality directly related to IA was 24%. The 100-day, 2-year and 10-year overall survival were 42.9%, 0%, 0% in allo-SCT recipients compared to 68.1%, 18.2%, 13.6% in leukemia patients, respectively (P≥0.05). These poor outcomes were mainly attributable to non-relapse mortality (NRM). In conclusion, our data allows distinguishing 2 types of IA occurring at different time in the treatment course. In both cases, the NRM is very high and treatment remains challenging. Thus, systematic broad-spectrum AP against Aspergillus should be considered in acute leukemia patients during the neutropenic phase and in all patients undergoing allo-SCT who develop GVHD.