Chair of Hematology, Department of Internal Medicine (DiMI), University of Genoa
Contributions
Type: Publication Only
Background
Prevention and prompt treatment of invasive fungal infections (IFI) in acute myeloid leukemia (AML) patients can improve overall survival by reducing infection-related mortality and allowing to receive full planned chemotherapy in a timely manner.
Aims
Since January 2013, AML patients undergoing intensive chemotherapy in our institute and potentially eligible for bone marrow transplantation received posaconazole (PSZ) as IFI prophylaxis. The aim of the present study was to evaluate tolerability and efficacy of PSZ and to optimize our clinical practice.
Methods
From January 2013 to October 2014, 35 patients treated for newly diagnosed AML in our institute received PSZ for antifungal prophylaxis.
Non promyelocytic AML patients received a fludarabine, cytarabine and idarubicin containing regimen (FLAI) as first line treatment. M3 AML patients were treated according to GIMEMA AIDA 2000 protocol.
PSZ was given at the standard dose of 200 mg for 3 times/day, concurrently with a fat snack or with at least 100 ml of an acidic drink. Because of unpredictable absorption rates PSZ serum levels (TDM) were assessed routinely according to a validated high-performance liquid chromato-graphic (HPLC) method as described. To detect factors affecting PSZ exposure we analyzed each period of hospitalization as a single independent event.
We retrospectively compared through a matched-paired analysis 22 non M3 AML patients treated with PSZ as IFI prophilaxys to a control historical series of 22 patients who had received fluconazole (FLC) or itraconazole (ITZ). Of 22 patients in PSZ cohort, 18 received subsequent induction cycle 2 and 6 received consolidation therapy, therefore accounting for a total of 46 episodes of prolonged neutropenia. In FLC/ITZ arm 22 patients received cycle 2 and 6 received consolidation therapy, for a total of 50 episodes of prolonged neutropenia. Matching variables were sex, age, response to induction. Patients median age, sex and days of severe neutropenia were not significantly different between the two cohorts. The incidence of IFI and the days of empirical or targeted intravenous antifungal therapy were analyzed.
Results
PSZ showed a good tolerability profile with no serious adverse events clearly related to prophylaxis occurring. A median number of 3 TDM for each period of hospitalization was performed (range 2-6). The achievement of a plasmatic PSZ concentration > 0,7 mcg/mL is considered optimal for prophylaxis efficacy; in 39/65 (60%) episodes of hospitalization and treatment, with at least two TDM, the threshold PSZ serum concentration was reached, with stable plasmatic levels. Median PSZ plasmatic value at first assessment was 0.73 mcg/mL (range 0.1-3.9).
The strongest negative factors affecting PSZ absorption are the temporary discontinuation of prophylaxis and the concomitant assumption of proton pump inhibitors.
No proven or probable IFI were observed in the PSZ cohort. Data coming out from the matched paired analysis demonstrated a significant reduction in IFI incidence in our institution: 0% in PSZ cohort Vs 12% (6 proven/probable IFI episodes over 50 severe neutropenic periods) in FLC/ITZ cohort (p<0.05). Mean days of targeted/empirical intravenous antifungal therapy for single patient in PSZ cohort was 0 days Vs 2.2 days in FLC/ITZ cohort (p<0.05).
Summary
Our clinical experience confirms the benefit and potential cost-effectiveness of primary prophylaxis with PSZ in AML patients receiving intensive treatment, as no patients in PSZ cohort experienced IFI nor received empirical intravenous antifungal therapy.
Keyword(s): Acute myeloid leukemia, Invasive aspergillosis, Prophylaxis
Session topic: Publication Only
Type: Publication Only
Background
Prevention and prompt treatment of invasive fungal infections (IFI) in acute myeloid leukemia (AML) patients can improve overall survival by reducing infection-related mortality and allowing to receive full planned chemotherapy in a timely manner.
Aims
Since January 2013, AML patients undergoing intensive chemotherapy in our institute and potentially eligible for bone marrow transplantation received posaconazole (PSZ) as IFI prophylaxis. The aim of the present study was to evaluate tolerability and efficacy of PSZ and to optimize our clinical practice.
Methods
From January 2013 to October 2014, 35 patients treated for newly diagnosed AML in our institute received PSZ for antifungal prophylaxis.
Non promyelocytic AML patients received a fludarabine, cytarabine and idarubicin containing regimen (FLAI) as first line treatment. M3 AML patients were treated according to GIMEMA AIDA 2000 protocol.
PSZ was given at the standard dose of 200 mg for 3 times/day, concurrently with a fat snack or with at least 100 ml of an acidic drink. Because of unpredictable absorption rates PSZ serum levels (TDM) were assessed routinely according to a validated high-performance liquid chromato-graphic (HPLC) method as described. To detect factors affecting PSZ exposure we analyzed each period of hospitalization as a single independent event.
We retrospectively compared through a matched-paired analysis 22 non M3 AML patients treated with PSZ as IFI prophilaxys to a control historical series of 22 patients who had received fluconazole (FLC) or itraconazole (ITZ). Of 22 patients in PSZ cohort, 18 received subsequent induction cycle 2 and 6 received consolidation therapy, therefore accounting for a total of 46 episodes of prolonged neutropenia. In FLC/ITZ arm 22 patients received cycle 2 and 6 received consolidation therapy, for a total of 50 episodes of prolonged neutropenia. Matching variables were sex, age, response to induction. Patients median age, sex and days of severe neutropenia were not significantly different between the two cohorts. The incidence of IFI and the days of empirical or targeted intravenous antifungal therapy were analyzed.
Results
PSZ showed a good tolerability profile with no serious adverse events clearly related to prophylaxis occurring. A median number of 3 TDM for each period of hospitalization was performed (range 2-6). The achievement of a plasmatic PSZ concentration > 0,7 mcg/mL is considered optimal for prophylaxis efficacy; in 39/65 (60%) episodes of hospitalization and treatment, with at least two TDM, the threshold PSZ serum concentration was reached, with stable plasmatic levels. Median PSZ plasmatic value at first assessment was 0.73 mcg/mL (range 0.1-3.9).
The strongest negative factors affecting PSZ absorption are the temporary discontinuation of prophylaxis and the concomitant assumption of proton pump inhibitors.
No proven or probable IFI were observed in the PSZ cohort. Data coming out from the matched paired analysis demonstrated a significant reduction in IFI incidence in our institution: 0% in PSZ cohort Vs 12% (6 proven/probable IFI episodes over 50 severe neutropenic periods) in FLC/ITZ cohort (p<0.05). Mean days of targeted/empirical intravenous antifungal therapy for single patient in PSZ cohort was 0 days Vs 2.2 days in FLC/ITZ cohort (p<0.05).
Summary
Our clinical experience confirms the benefit and potential cost-effectiveness of primary prophylaxis with PSZ in AML patients receiving intensive treatment, as no patients in PSZ cohort experienced IFI nor received empirical intravenous antifungal therapy.
Keyword(s): Acute myeloid leukemia, Invasive aspergillosis, Prophylaxis
Session topic: Publication Only