Results
Thirty three IFI episodes in 28 patients were examined. Two or more episodes were recorded in four patients. Demographic and clinical characteristics of the patients, and data for IFI were listed inTable 1 . None of the patients underwent hematopoietic stem cell transplantation prior to IFI onset. GM analysis was applied to all patients at the beginning of a febrile neutropenia attack and in the continuation in necessary patients, and was positive in 10 (32.3%) episodes. The mean GM index of the positive episodes was 3.27 ± 3.35 (0.74-9). The most common radiological findings were ground-glass view (75.8%), nodules (54.5%) and consolidations (24.3%). Cavitation and/or halo sign were recorded in 7 episodes. All 27 episodes that were detected any radiological finding were pulmonary IFI; the remainder were hepatosplenic (in 2 episodes), central nervous system (in 1 episode), and paranasal (in 1 episode) involvement, respectively.
Liposomal amphotericin B (LAmB) was the first antifungal agent for monotherapy in 16 (50%) of IFI episodes, caspofungin in 11 (34.4%), and voriconazole in 5 (15.6%) episodes. Mean duration of monotherapy was 12.84 ± 4.28 (5-24) days. The second antifungal was added because of insufficient response at all episodes, and preferences were listed as follows: voriconazole in 22 (68.7%) patients, LAmB in 7 (21.8%) patients, caspofungin in 2 (6.4%) patients, and posaconazole in 1 (3.2%) patient. CAT was initiated directly in only one episode as voriconazole plus caspofungin. Preferred combination regimes; duration of therapy, treatment responses, and mortality rates were summarized inTable 2 . Range for treatment duration with combined antifungal was 15-67 days, and the range of transition day from combined regimen to monotherapy in surviving patients was 28-67 days. The effect of the combination regimen type on mortality was found to be statistically insignificant (z = 1.3; p = 0.192). In both of the proven IFI episodes, the causative agents were Candida spp .
The 12-week and overall survival rate of the patients was 75% and 39.2%, repectively. The cause of death was IFI progression in 13 of the 17 patients, and the remaining patients had non-responsiveness to underlying disease treatment. IFI attributable mortality rate was 76.5%. Mortality rate was significantly higher in patients with relapse (χ2 = 7.47; p = 0.006). Complete response (CR) to the treatment was obtained in 9 (81.8%) of 11 surviving patients. Mean recovery time in patients with CR was 96.45 ± 57.95 (48-210) days. Neutropenia duration (z = 0.39; p = 0.695), duration of CAT (z = 1.37;p = 0.173), and recovery time (z =0.768; p = 0.443) were not found statistically different in the episodes with/without death. The effect of the selected primary antifungal agent could not be evaluated due to insufficient number of cases. Duration of neutropenia (z = 0.22; p = 0.821) and CAT (t = 0.795; p = 0.446), and recovery time (t = 0.991; p = 0.355) were also not statistically different according to relapse or remission status. There was no statistically significant relationship between IFI classification and the episodes with/without death (χ2 = 3.726; p = 0.293). Among the surviving patients, voriconazole was preferred in 9 patients as the secondary antifungal prophylactic agent, and posaconazole in two patients.
CAT was well tolerated in most patients. Renal dysfunction accompanied by electrolyte disturbances in one patient and increased transaminases in two patients were seen as adverse effects of CAT, and treatment discontinuation was required in only one patient because of side effects. Plasma levels monitoring for voriconazole was not provided since not implemented in our center. IFI-induced surgical procedure was not applied to any patient.