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Finally, the small number of patients, the lack of sensitivity of the pan-fungal PCR, and the once-a-week screening do not permit conclusions to be drawn on the relevance of the strategy. In France, we ran a randomized trial comparing a purely empirical versus a pre-emptive approach in 293 high-risk neutropenic patients [31, 39]. With 67% of AML patients, the median duration of neutropenia Selleckchem Bafilomycin A1 in the case of predefined clinical symptoms or septic shock. Overall survival at day 42 after inclusion (primary FMO5 endpoint) was not statistically different in both groups (97% in the empirical group vs 95% in the pre-emptive group). As expected, amphotericin-B was given to fewer patients and for shorter durations in the pre-emptive group. However, two main issues pushed our group to go further: (i) the incidence of proven/probable IFD was significantly higher in the pre-emptive group both in the whole population (9.1% vs 2.7%; p?www.selleckchem.com/products/pf-06463922.html of the pre-emptive approach on overall survival. Knowing the high risk of IFD in this subgroup of patients, any doubts concerning a loss in survival or gain of IFD risk makes it difficult to implement the pre-emptive strategy without further studies. Second, the difference in IFD incidence cannot be considered as incidental because this may impact on outcome [6]. A similar trial was run by Tan et?al. [34] but was underpowered to draw any conclusion. Recently, Morrissey et?al. compared a hybrid empirical approach (fever and CT scan driven), with a hybrid pre-emptive approach using twice-weekly blood testing with GM and two-nested PCR qualitative assays targeting Aspergillus spp. A CT scan was performed in the case of positive biomarker(s) or of persistent fever [33]. Among the 240 included patients, most were allogeneic HSCT recipients. The choice of antifungals was left to the initiative of the investigator. The use of empirical antifungal drugs at week 26 (the primary endpoint) was significantly lower in the pre-emptive compared with the empirical group (15% vs 32%; p?0.002). Overall survival was not different between groups but the trial was not powered to assess survival. IFD, and especially probable IA, were significantly more frequent in the pre-emptive group than in the standard group (24.5% vs 4.1%; p?