PRIMARY ANTIFUNGAL PROPHYLAXIS (PAP) WITH MICAFUNGIN AT THE DOSE 50MG PER DAY IN ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL) DURING INDUCTION CHEMOTHERAPY: THE „REAL-LIFE“ EVALUATION
(Abstract release date: 05/19/16)
EHA Library. Kabut T. 06/09/16; 132736; E1187
Dr. Tomas Kabut
Contributions
Contributions
Abstract
Abstract: E1187
Type: Eposter Presentation
Background
Invasive fungal diseases (IFDs) during treatment of acute leukaemias are associated with a high morbidity and mortality. While in patients with acute myelogenous leukaemia PAP during induction treatment is well established (mainly with posaconazole), standardized PAP in patients with ALL is lacking. The major obstacle represents the risk of interactions of mould active azoles with chemotherapy agents during the intensive treatment of ALL. Thus the choice of PAP in these patients is difficult and they frequently remain without mould active PAP.
Aims
Evaluation of the efficacy and safety of micafungin PAP (dose 50mg/day) in adult patients with ALL during the induction chemotherapy.
Methods
A retrospective analysis of patients with ALL (or T-lymphoblastic lymphoma or Burkitt's leukaemia/lymphoma) treated with intensive ALL (or ALL- like) protocols in 2 tertiary care haematological centres in the Czech Republic receiving PAP with micafungin. Patients received micafungin (50 mg/day) from the start of induction chemotherapy till the neutrophils recovery. EORTC/MSG 2008 criteria for IFD diagnosis were used. CCTCAE v 4.0 criteria were used for evaluation of safety of PAP.
Results
Forty- nine patients received micafungin PAP 50 mg/day during induction chemotherapy of ALL between 2012 and 2015. ALL-CELL 2012 Junior protocol was used in 39 patients, GMALL B-ALL/NHL 2002 protocol in 3 patients and ALL-CELL 2012 elderly or EWALL Elderly protocol in 7 patients. The mean length of micafungin prophylaxis was 22 days (2-80 days).Antifungal prophylaxis failed in 2/49 (4.1%) patients, who developed IFD. Both patients developed proven IFD, no episode of probable IFD occurred. Both patients with proven IFD were successfully treated with combination of antifungal agents. One proven IFD had a form of invasive pulmonary aspergillosis (histologically proven and confirmed by PCR identification, culture negative) and occurred only early after the initiation of PAP (day 4). Second proven IFD represented disseminated Geotrichum capitatum infection (blood culture, liver and spleen) with MIC 32 μg/ml for echinocandins.Apart from the 2 IFD episodes, 10/49 (20.4%) patients developed pulmonary infiltrates – 3/49 (6.1%) specific for IFD based on EORTC/MSG 2008 criteria (without any microbiological criteria and thus fulfilling criteria for possible IFD) and 7/49 (14.3%) non-specific pulmonary infiltrates.Empirical antifungal therapy was initiated in 10/49 patients (20.4%). As an empirical therapy micafungin at dose 100mg/day was used in 8/10 patients, voriconazole in 1/10 patients and lipid based amphotericin B in 1/10 patient.All 49/49 (100%) patients developed liver function test (LFT) elevation at least grade 1-2. However 63% patients had pre-existing liver test elevations. None of these LFT elevations were concluded as probably or definitely associated with micafungin and none required an interruption of micafungin prophylaxis.
Conclusion
Our real-life data proved efficacy of micafungin 50 mg/day as PAP in this population of patients at high risk of IFD, but also at high risk of drug-drug interactions. Only 2 (4.1%) patients developed breakthrough IFD, however in 1 case in a very early stage of PAP. The elevation of LFTs represented a major limitation of the prophylaxis, but was most likely associated with a therapy of ALL and did not require an interruption of micafungin PAP. Echinocandine-based PAP could represent a safe option for prophylaxis of this difficult to treat population of patients with ALL.
Session topic: E-poster
Keyword(s): ALL, Fungal infection, Prophylaxis
Type: Eposter Presentation
Background
Invasive fungal diseases (IFDs) during treatment of acute leukaemias are associated with a high morbidity and mortality. While in patients with acute myelogenous leukaemia PAP during induction treatment is well established (mainly with posaconazole), standardized PAP in patients with ALL is lacking. The major obstacle represents the risk of interactions of mould active azoles with chemotherapy agents during the intensive treatment of ALL. Thus the choice of PAP in these patients is difficult and they frequently remain without mould active PAP.
Aims
Evaluation of the efficacy and safety of micafungin PAP (dose 50mg/day) in adult patients with ALL during the induction chemotherapy.
Methods
A retrospective analysis of patients with ALL (or T-lymphoblastic lymphoma or Burkitt's leukaemia/lymphoma) treated with intensive ALL (or ALL- like) protocols in 2 tertiary care haematological centres in the Czech Republic receiving PAP with micafungin. Patients received micafungin (50 mg/day) from the start of induction chemotherapy till the neutrophils recovery. EORTC/MSG 2008 criteria for IFD diagnosis were used. CCTCAE v 4.0 criteria were used for evaluation of safety of PAP.
Results
Forty- nine patients received micafungin PAP 50 mg/day during induction chemotherapy of ALL between 2012 and 2015. ALL-CELL 2012 Junior protocol was used in 39 patients, GMALL B-ALL/NHL 2002 protocol in 3 patients and ALL-CELL 2012 elderly or EWALL Elderly protocol in 7 patients. The mean length of micafungin prophylaxis was 22 days (2-80 days).Antifungal prophylaxis failed in 2/49 (4.1%) patients, who developed IFD. Both patients developed proven IFD, no episode of probable IFD occurred. Both patients with proven IFD were successfully treated with combination of antifungal agents. One proven IFD had a form of invasive pulmonary aspergillosis (histologically proven and confirmed by PCR identification, culture negative) and occurred only early after the initiation of PAP (day 4). Second proven IFD represented disseminated Geotrichum capitatum infection (blood culture, liver and spleen) with MIC 32 μg/ml for echinocandins.Apart from the 2 IFD episodes, 10/49 (20.4%) patients developed pulmonary infiltrates – 3/49 (6.1%) specific for IFD based on EORTC/MSG 2008 criteria (without any microbiological criteria and thus fulfilling criteria for possible IFD) and 7/49 (14.3%) non-specific pulmonary infiltrates.Empirical antifungal therapy was initiated in 10/49 patients (20.4%). As an empirical therapy micafungin at dose 100mg/day was used in 8/10 patients, voriconazole in 1/10 patients and lipid based amphotericin B in 1/10 patient.All 49/49 (100%) patients developed liver function test (LFT) elevation at least grade 1-2. However 63% patients had pre-existing liver test elevations. None of these LFT elevations were concluded as probably or definitely associated with micafungin and none required an interruption of micafungin prophylaxis.
Conclusion
Our real-life data proved efficacy of micafungin 50 mg/day as PAP in this population of patients at high risk of IFD, but also at high risk of drug-drug interactions. Only 2 (4.1%) patients developed breakthrough IFD, however in 1 case in a very early stage of PAP. The elevation of LFTs represented a major limitation of the prophylaxis, but was most likely associated with a therapy of ALL and did not require an interruption of micafungin PAP. Echinocandine-based PAP could represent a safe option for prophylaxis of this difficult to treat population of patients with ALL.
Session topic: E-poster
Keyword(s): ALL, Fungal infection, Prophylaxis
Abstract: E1187
Type: Eposter Presentation
Background
Invasive fungal diseases (IFDs) during treatment of acute leukaemias are associated with a high morbidity and mortality. While in patients with acute myelogenous leukaemia PAP during induction treatment is well established (mainly with posaconazole), standardized PAP in patients with ALL is lacking. The major obstacle represents the risk of interactions of mould active azoles with chemotherapy agents during the intensive treatment of ALL. Thus the choice of PAP in these patients is difficult and they frequently remain without mould active PAP.
Aims
Evaluation of the efficacy and safety of micafungin PAP (dose 50mg/day) in adult patients with ALL during the induction chemotherapy.
Methods
A retrospective analysis of patients with ALL (or T-lymphoblastic lymphoma or Burkitt's leukaemia/lymphoma) treated with intensive ALL (or ALL- like) protocols in 2 tertiary care haematological centres in the Czech Republic receiving PAP with micafungin. Patients received micafungin (50 mg/day) from the start of induction chemotherapy till the neutrophils recovery. EORTC/MSG 2008 criteria for IFD diagnosis were used. CCTCAE v 4.0 criteria were used for evaluation of safety of PAP.
Results
Forty- nine patients received micafungin PAP 50 mg/day during induction chemotherapy of ALL between 2012 and 2015. ALL-CELL 2012 Junior protocol was used in 39 patients, GMALL B-ALL/NHL 2002 protocol in 3 patients and ALL-CELL 2012 elderly or EWALL Elderly protocol in 7 patients. The mean length of micafungin prophylaxis was 22 days (2-80 days).Antifungal prophylaxis failed in 2/49 (4.1%) patients, who developed IFD. Both patients developed proven IFD, no episode of probable IFD occurred. Both patients with proven IFD were successfully treated with combination of antifungal agents. One proven IFD had a form of invasive pulmonary aspergillosis (histologically proven and confirmed by PCR identification, culture negative) and occurred only early after the initiation of PAP (day 4). Second proven IFD represented disseminated Geotrichum capitatum infection (blood culture, liver and spleen) with MIC 32 μg/ml for echinocandins.Apart from the 2 IFD episodes, 10/49 (20.4%) patients developed pulmonary infiltrates – 3/49 (6.1%) specific for IFD based on EORTC/MSG 2008 criteria (without any microbiological criteria and thus fulfilling criteria for possible IFD) and 7/49 (14.3%) non-specific pulmonary infiltrates.Empirical antifungal therapy was initiated in 10/49 patients (20.4%). As an empirical therapy micafungin at dose 100mg/day was used in 8/10 patients, voriconazole in 1/10 patients and lipid based amphotericin B in 1/10 patient.All 49/49 (100%) patients developed liver function test (LFT) elevation at least grade 1-2. However 63% patients had pre-existing liver test elevations. None of these LFT elevations were concluded as probably or definitely associated with micafungin and none required an interruption of micafungin prophylaxis.
Conclusion
Our real-life data proved efficacy of micafungin 50 mg/day as PAP in this population of patients at high risk of IFD, but also at high risk of drug-drug interactions. Only 2 (4.1%) patients developed breakthrough IFD, however in 1 case in a very early stage of PAP. The elevation of LFTs represented a major limitation of the prophylaxis, but was most likely associated with a therapy of ALL and did not require an interruption of micafungin PAP. Echinocandine-based PAP could represent a safe option for prophylaxis of this difficult to treat population of patients with ALL.
Session topic: E-poster
Keyword(s): ALL, Fungal infection, Prophylaxis
Type: Eposter Presentation
Background
Invasive fungal diseases (IFDs) during treatment of acute leukaemias are associated with a high morbidity and mortality. While in patients with acute myelogenous leukaemia PAP during induction treatment is well established (mainly with posaconazole), standardized PAP in patients with ALL is lacking. The major obstacle represents the risk of interactions of mould active azoles with chemotherapy agents during the intensive treatment of ALL. Thus the choice of PAP in these patients is difficult and they frequently remain without mould active PAP.
Aims
Evaluation of the efficacy and safety of micafungin PAP (dose 50mg/day) in adult patients with ALL during the induction chemotherapy.
Methods
A retrospective analysis of patients with ALL (or T-lymphoblastic lymphoma or Burkitt's leukaemia/lymphoma) treated with intensive ALL (or ALL- like) protocols in 2 tertiary care haematological centres in the Czech Republic receiving PAP with micafungin. Patients received micafungin (50 mg/day) from the start of induction chemotherapy till the neutrophils recovery. EORTC/MSG 2008 criteria for IFD diagnosis were used. CCTCAE v 4.0 criteria were used for evaluation of safety of PAP.
Results
Forty- nine patients received micafungin PAP 50 mg/day during induction chemotherapy of ALL between 2012 and 2015. ALL-CELL 2012 Junior protocol was used in 39 patients, GMALL B-ALL/NHL 2002 protocol in 3 patients and ALL-CELL 2012 elderly or EWALL Elderly protocol in 7 patients. The mean length of micafungin prophylaxis was 22 days (2-80 days).Antifungal prophylaxis failed in 2/49 (4.1%) patients, who developed IFD. Both patients developed proven IFD, no episode of probable IFD occurred. Both patients with proven IFD were successfully treated with combination of antifungal agents. One proven IFD had a form of invasive pulmonary aspergillosis (histologically proven and confirmed by PCR identification, culture negative) and occurred only early after the initiation of PAP (day 4). Second proven IFD represented disseminated Geotrichum capitatum infection (blood culture, liver and spleen) with MIC 32 μg/ml for echinocandins.Apart from the 2 IFD episodes, 10/49 (20.4%) patients developed pulmonary infiltrates – 3/49 (6.1%) specific for IFD based on EORTC/MSG 2008 criteria (without any microbiological criteria and thus fulfilling criteria for possible IFD) and 7/49 (14.3%) non-specific pulmonary infiltrates.Empirical antifungal therapy was initiated in 10/49 patients (20.4%). As an empirical therapy micafungin at dose 100mg/day was used in 8/10 patients, voriconazole in 1/10 patients and lipid based amphotericin B in 1/10 patient.All 49/49 (100%) patients developed liver function test (LFT) elevation at least grade 1-2. However 63% patients had pre-existing liver test elevations. None of these LFT elevations were concluded as probably or definitely associated with micafungin and none required an interruption of micafungin prophylaxis.
Conclusion
Our real-life data proved efficacy of micafungin 50 mg/day as PAP in this population of patients at high risk of IFD, but also at high risk of drug-drug interactions. Only 2 (4.1%) patients developed breakthrough IFD, however in 1 case in a very early stage of PAP. The elevation of LFTs represented a major limitation of the prophylaxis, but was most likely associated with a therapy of ALL and did not require an interruption of micafungin PAP. Echinocandine-based PAP could represent a safe option for prophylaxis of this difficult to treat population of patients with ALL.
Session topic: E-poster
Keyword(s): ALL, Fungal infection, Prophylaxis
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