Introduction
Fungal Infections (FI) of the Central Nervous System (FI-CNS) and Paranasal Sinuses (FI-PS) are rare life-threatening infections in hematologic patients (pts) and their management remains a challenge despite availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohort of pts focusing on these rare FI, are still lacking.
Between January 2010 and December 2016, 87 cases of Proven (51) or Probable (36) FI-CNS (69/87) or FI-PS (18/87) were collected in 26 Hematological Centers. Median age of pts was 40 yrs (3-79) and 22/87-25% had less than 18 yrs. Acute Leukemia (AML or ALL) was the most common underlying disease (59/87, 68%) and 25/87-29% cases received a previous Allo-SCT. Aspergillus sp was the most common pathogen (61 cases, 70%), followed by Zygomycetes (18 cases, 21%), Criptococcus sp (4 cases, 5%) and Fusarium sp (2 cases, 2%). The lung was the primary focus of FI in 48% of cases. The CNS biopsy was performed in 7/69-10% of FI-CNS cases and a sinus biopsy was done in 10/18-56% of FI-PS (p= 0,03). The GM Test on cerebrospinal fluid (CSF) has been performed in 41% of FI-CNS (28/69) and it was positive in 20/28-71%. Eighty-four pts received a first line antifungal therapy (AT) with Amphotericine B (mainly L-AMB) in 56/84-67% of cases and Voriconazole in 35/84-42%. Moreover, 56% of pts received 2 or more lines of AT and 43% were treated with a combination of 2 or more antifungal drugs. The median duration of AT was 58 days (range 1-835).A surgical intervention was performed in 21/87-24% of cases but only 7/69-10% of FI-CNS underwent neurosurgical intervention. The ORR to treatment (complete and partial responses) was 56% (CR 34% and PR 22%). The median OS after FI-CNS and FI-PS was 4,7 and 3,3 mths, respectively (P=ns). One year OS was 31% without significant differences between FI-CNS and FI-PS. Outcome according a multifactor risk analysis (including age, status and type of underling disease, allo-SCT, PMN at baseline and recovery, lines and duration of AT, surgical intervention, etc) has been evaluated. The FI attributable mortality was 33%.
To summarize, mortality of FI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of new antifungal drugs. The results arising from the analysis of this large cohort of cases, may allow a more effective management of these rare FI complications in hematologic pts.
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