Invasive fungal infections in patients with acute myeloid leukemia and in those submitted to allogeneic hemopoietic stem cell transplant: who is at highest risk?

To the Editor: Invasive fungal infections (IFIs) are a growing cause of morbidity and mortality in patients with acute myeloid leukemia (AMLs) and in recipients of allogeneic hemopoietic stem cell transplantation (allo-HSCTs) (1–6). It is widely debated if either allo-HSCTs or AMLs are to be considered at higher risk, but no data comparing the two categories of patients have been reported in literature so far. This cohort study has been conducted from January 1999 to December 2003 in hematology wards located throughout Italy. The study was aimed at evaluating the incidence and mortality for IFIs in adult AMLs and in patients submitted to all types of allo-HSCT procedures; a comparison between the two categories of patients was carried out. EORTC ⁄MSG consensus criteria were used to define IFIs (7). Only infections that were classified as ‘proven’ or ‘probable’ were included in the data analysis. Overall and IFI-attributable mortality rates (IFI-AMR) were estimated. IFI-AMR was defined as a progression of sepsis-related symptoms or of the involved organ failure in the absence of other morbid condition thought to cause death. Outcome was assessed on the 150th day after IFI diagnosis. During the 5-yr study, 1596 new patients received intensive chemotherapy for AML and 679 were submitted to allo-HSCT procedures in the nine participating centers. Proven or probable IFIs were documented in 270 AMLs (174 moulds and 96 yeasts) (incidence 16.9%) and in 56 allo-HSCTs (43 moulds and 13 yeasts) (incidence 8.2%). All yeast infections were sustained by Candida spp. Conversely, mould infections were mostly caused by Aspergillus spp (96% in AML and 91% in HSCT); only a few cases due to rare agents were observed. Significant differences emerged from the comparison of IFI incidence rates in AMLs and allo-HSCTs. The overall mortality rate for fungal infection was 5.9% in AMLs and 5.7% in allo-HSCTs, with an IFI-AMR of 34.8% and 69.6% respectively (Table 1). Furthermore, we separately analyzed mould and yeast infections. In yeast infections, the incidence was higher in AMLs (P-value <0.001), while differences in AMR were not statistically significant (P-value 0.105). As for moulds, significant differences in both incidence rate and AMR were found in AMLs and allo-HSCTs (P-value <0.001). Data about mortality rate became more impressive after having compared AML patients treated with chemotherapy (174 pts) to those treated with allo-HSCT (21 pts). Mortality reached 90.5% in transplanted patients (RR 2.58, CI95% 2.02–3.3, P-value <0.001). IFIs appeared both during the early and late phase after allo-HSCT. Interestingly in moulds infections only, AMR resulted higher for those infections occurring within 100 d from transplant (AMR 85% in early vs. 56% in late aspergillosis, P-value 0.04); it means that patients receiving allo-HSCT continue to be at risk for IFIs even after 100 d, but risk of mortality decreases during the post-engraftment phase.