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.