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Aurelio Maggio - One of the best experts on this subject based on the ideXlab platform.
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deferiprone versus Deferoxamine in thalassemia intermedia results from a 5 year long term italian multicenter randomized clinical trial
American Journal of Hematology, 2015Co-Authors: Giuseppina Calvaruso, Angela Vitrano, Rosario Di Maggio, Grazia Colletta, Alessandra Quota, Massimiliano Sacco, Calogera Gerardi, Luciana Rigoli, Lorella Pitrolo, Aurelio MaggioAbstract:In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are Deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus Deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value = 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the Deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the Deferoxamine treatment (P-value = 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of Deferoxamine, suggesting that this drug is an alternative option in cases in which Deferoxamine and deferasirox are contraindicated. Am. J. Hematol. 90:634–638, 2015. © 2015 Wiley Periodicals, Inc.
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improving survival with deferiprone treatment in patients with thalassemia major a prospective multicenter randomised clinical trial under the auspices of the italian society for thalassemia and hemoglobinopathies
Blood Cells Molecules and Diseases, 2009Co-Authors: Aurelio Maggio, Angela Vitrano, Marcello Capra, Liana Cuccia, Francesco Gagliardotto, Aldo Filosa, Carmelo Magnano, Michele Rizzo, Vincenzo Caruso, Calogera GerardiAbstract:Abstract The prognosis for thalassemia major has dramatically improved in the last two decades. However, many transfusion-dependent patients continue to develop progressive accumulation of iron. This can lead to tissue damage and eventually death, particularly from cardiac disease. Previous studies that investigated iron chelation treatments, including retrospective and prospective non-randomised clinical trials, suggested that mortality, due mainly to cardiac damage, was reduced or completely absent in patients treated with deferiprone (DFP) alone or a combined deferiprone–Deferoxamine (DFP–DFO) chelation treatment. However, no survival analysis has been reported for a long-term randomised control trial. Here, we performed a multicenter, long-term, randomised control trial that compared Deferoxamine (DFO) versus DFP alone, sequential DFP–DFO, or combined DFP–DFO iron chelation treatments. The trial included 265 patients with thalassemia major, with 128 (48.3%) females and 137 (51.7%) males. No deaths occurred with the DFP-alone or the combined DFP–DFO treatments. One death occurred due to graft versus host disease (GVHD) in a patient that had undergone bone marrow transplantation; this patient was censored at the time of transplant. Only one death occurred with the DFP–DFO sequential treatment in a patient that had experienced an episode of heart failure one year earlier. Ten deaths occurred with the Deferoxamine treatment. The main factors that correlated with an increase in the hazard ratio for death were: cirrhosis, arrhythmia, previous episode of heart failure, diabetes, hypogonadism, and hypothyroidism. In a Cox regression model, the interaction effect of sex and age was statistically significant ( p -value p -value In conclusion, the results of this study show that the risk factors for predicting mortality in patients with thalassemia major are Deferoxamine-treatment, complications, and the interaction effect of sex and age.
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light and shadows in the iron chelation treatment of haematological diseases
British Journal of Haematology, 2007Co-Authors: Aurelio MaggioAbstract:This review outlines the main chelator groups studied to date, and the evidence for their clinical effectiveness. For each treatment, the strength of evidence was documented according to the guidelines from the American College of Cardiology and the American Heart Association. Three main haematological diseases were considered as models: thalassaemia major, sickle-cell disorders and myelodysplasia. Although the data in the literature do not allow firmly evidence-based conclusions, the findings suggest that in thalassaemia major: (i) Deferoxamine remains the drug of choice for chelation treatment; (ii) if there is Deferoxamine intolerance or a change of treatment is suggested, the options are deferiprone or, if the liver iron concentration is high, deferasirox treatment; and (iii) if the ferritin level is >2500 microg/l and liver iron concentation is >7 mg/g/dry weight, continuous subcutaneous (s.c.) or intravenous (i.v.) Deferoxamine, or combined treatment with deferiprone and Deferoxamine is advised. In case of heart failure, there is currently more solid documentation to support continuous s.c. or i.v. Deferoxamine treatment than combined treatment with deferiprone and Deferoxamine. However, more recent data in the literature suggest that the latter could be a satisfactory alternative. Finally, if iron chelation is required for sickle-cell disorders or myelodysplastic syndromes, the current data support the use of Deferoxamine treatment.
Calogera Gerardi - One of the best experts on this subject based on the ideXlab platform.
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deferiprone versus Deferoxamine in thalassemia intermedia results from a 5 year long term italian multicenter randomized clinical trial
American Journal of Hematology, 2015Co-Authors: Giuseppina Calvaruso, Angela Vitrano, Rosario Di Maggio, Grazia Colletta, Alessandra Quota, Massimiliano Sacco, Calogera Gerardi, Luciana Rigoli, Lorella Pitrolo, Aurelio MaggioAbstract:In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are Deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus Deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value = 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the Deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the Deferoxamine treatment (P-value = 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of Deferoxamine, suggesting that this drug is an alternative option in cases in which Deferoxamine and deferasirox are contraindicated. Am. J. Hematol. 90:634–638, 2015. © 2015 Wiley Periodicals, Inc.
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deferiprone versus Deferoxamine in thalassemia intermedia results from a 5 year long term italian multicenter randomized clinical trial
American Journal of Hematology, 2015Co-Authors: Giuseppina Calvaruso, Angela Vitrano, Rosario Di Maggio, Grazia Colletta, Alessandra Quota, Massimiliano Sacco, Calogera Gerardi, Luciana Rigoli, Eliana Lai, Lorella PitroloAbstract:In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are Deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus Deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value = 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the Deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the Deferoxamine treatment (P-value = 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of Deferoxamine, suggesting that this drug is an alternative option in cases in which Deferoxamine and deferasirox are contraindicated.
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improving survival with deferiprone treatment in patients with thalassemia major a prospective multicenter randomised clinical trial under the auspices of the italian society for thalassemia and hemoglobinopathies
Blood Cells Molecules and Diseases, 2009Co-Authors: Aurelio Maggio, Angela Vitrano, Marcello Capra, Liana Cuccia, Francesco Gagliardotto, Aldo Filosa, Carmelo Magnano, Michele Rizzo, Vincenzo Caruso, Calogera GerardiAbstract:Abstract The prognosis for thalassemia major has dramatically improved in the last two decades. However, many transfusion-dependent patients continue to develop progressive accumulation of iron. This can lead to tissue damage and eventually death, particularly from cardiac disease. Previous studies that investigated iron chelation treatments, including retrospective and prospective non-randomised clinical trials, suggested that mortality, due mainly to cardiac damage, was reduced or completely absent in patients treated with deferiprone (DFP) alone or a combined deferiprone–Deferoxamine (DFP–DFO) chelation treatment. However, no survival analysis has been reported for a long-term randomised control trial. Here, we performed a multicenter, long-term, randomised control trial that compared Deferoxamine (DFO) versus DFP alone, sequential DFP–DFO, or combined DFP–DFO iron chelation treatments. The trial included 265 patients with thalassemia major, with 128 (48.3%) females and 137 (51.7%) males. No deaths occurred with the DFP-alone or the combined DFP–DFO treatments. One death occurred due to graft versus host disease (GVHD) in a patient that had undergone bone marrow transplantation; this patient was censored at the time of transplant. Only one death occurred with the DFP–DFO sequential treatment in a patient that had experienced an episode of heart failure one year earlier. Ten deaths occurred with the Deferoxamine treatment. The main factors that correlated with an increase in the hazard ratio for death were: cirrhosis, arrhythmia, previous episode of heart failure, diabetes, hypogonadism, and hypothyroidism. In a Cox regression model, the interaction effect of sex and age was statistically significant ( p -value p -value In conclusion, the results of this study show that the risk factors for predicting mortality in patients with thalassemia major are Deferoxamine-treatment, complications, and the interaction effect of sex and age.
Lorella Pitrolo - One of the best experts on this subject based on the ideXlab platform.
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deferiprone versus Deferoxamine in thalassemia intermedia results from a 5 year long term italian multicenter randomized clinical trial
American Journal of Hematology, 2015Co-Authors: Giuseppina Calvaruso, Angela Vitrano, Rosario Di Maggio, Grazia Colletta, Alessandra Quota, Massimiliano Sacco, Calogera Gerardi, Luciana Rigoli, Lorella Pitrolo, Aurelio MaggioAbstract:In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are Deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus Deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value = 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the Deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the Deferoxamine treatment (P-value = 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of Deferoxamine, suggesting that this drug is an alternative option in cases in which Deferoxamine and deferasirox are contraindicated. Am. J. Hematol. 90:634–638, 2015. © 2015 Wiley Periodicals, Inc.
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deferiprone versus Deferoxamine in thalassemia intermedia results from a 5 year long term italian multicenter randomized clinical trial
American Journal of Hematology, 2015Co-Authors: Giuseppina Calvaruso, Angela Vitrano, Rosario Di Maggio, Grazia Colletta, Alessandra Quota, Massimiliano Sacco, Calogera Gerardi, Luciana Rigoli, Eliana Lai, Lorella PitroloAbstract:In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are Deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus Deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value = 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the Deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the Deferoxamine treatment (P-value = 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of Deferoxamine, suggesting that this drug is an alternative option in cases in which Deferoxamine and deferasirox are contraindicated.
Max Costa - One of the best experts on this subject based on the ideXlab platform.
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egr 1 mediates hypoxia inducible transcription of the ndrg1 gene through an overlapping egr 1 sp1 binding site in the promoter
Cancer Research, 2007Co-Authors: Ping Zhang, Kammeng Tchouwong, Max CostaAbstract:N-myc down-regulated gene 1 ( NDRG1/Cap43 ) is inducible by a variety of environmental stressors, including hypoxia. The present study identified a cis -acting element mediating the transactivation of the NDRG1 gene in murine RAW264.7 macrophage cells treated with hypoxia or Deferoxamine, an iron chelator mimicking hypoxia. Through a series of deletions of the promoter of NDRG1 luciferase constructs, a minimal cis -acting element conferring inducibility by hypoxia and Deferoxamine was localized to an early growth response 1 (Egr-1) and Sp1 overlapping binding site. Electrophoretic mobility shift assay, antibody supershift assay, and mutations of the Egr-1 binding site confirmed the specific binding of Egr-1 protein to this Egr-1/Sp1 motif. In addition, hypoxia increased the level of Egr-1 protein that correlated with induction of NDRG1 expression at both RNA and protein levels. Transient transfection of the Egr-1 gene into HeLa cells also resulted in up-regulation of the NDRG1 mRNA. The role of Egr-1 was further verified by mutations in the Egr-1 binding site, which reduced promoter inducibility by hypoxia and Deferoxamine. Furthermore, the induction of NDRG1 expression by hypoxia and Deferoxamine was diminished by RNA interference knockdown of Egr-1 gene expression and in Egr-1 −/− mouse embryonic fibroblasts (MEF) compared with Egr-1 +/− MEFs. These results showed for the first time that Egr-1 regulates NDRG1 transcription through an overlapping Egr-1/Sp1 binding site that acts as a major site of positive regulation of the NDRG1 promoter by hypoxia signaling. [Cancer Res 2007;67(19):9125–33]
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egr 1 mediates hypoxia inducible transcription of the ndrg1 gene through an overlapping egr 1 sp1 binding site in the promoter
Cancer Research, 2007Co-Authors: Ping Zhang, Kammeng Tchouwong, Max CostaAbstract:N-myc down-regulated gene 1 (NDRG1/Cap43) is inducible by a variety of environmental stressors, including hypoxia. The present study identified a cis-acting element mediating the transactivation of the NDRG1 gene in murine RAW264.7 macrophage cells treated with hypoxia or Deferoxamine, an iron chelator mimicking hypoxia. Through a series of deletions of the promoter of NDRG1 luciferase constructs, a minimal cis-acting element conferring inducibility by hypoxia and Deferoxamine was localized to an early growth response 1 (Egr-1) and Sp1 overlapping binding site. Electrophoretic mobility shift assay, antibody supershift assay, and mutations of the Egr-1 binding site confirmed the specific binding of Egr-1 protein to this Egr-1/Sp1 motif. In addition, hypoxia increased the level of Egr-1 protein that correlated with induction of NDRG1 expression at both RNA and protein levels. Transient transfection of the Egr-1 gene into HeLa cells also resulted in up-regulation of the NDRG1 mRNA. The role of Egr-1 was further verified by mutations in the Egr-1 binding site, which reduced promoter inducibility by hypoxia and Deferoxamine. Furthermore, the induction of NDRG1 expression by hypoxia and Deferoxamine was diminished by RNA interference knockdown of Egr-1 gene expression and in Egr-1-/- mouse embryonic fibroblasts (MEF) compared with Egr-1+/- MEFs. These results showed for the first time that Egr-1 regulates NDRG1 transcription through an overlapping Egr-1/Sp1 binding site that acts as a major site of positive regulation of the NDRG1 promoter by hypoxia signaling.
Angela Vitrano - One of the best experts on this subject based on the ideXlab platform.
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deferiprone versus Deferoxamine in thalassemia intermedia results from a 5 year long term italian multicenter randomized clinical trial
American Journal of Hematology, 2015Co-Authors: Giuseppina Calvaruso, Angela Vitrano, Rosario Di Maggio, Grazia Colletta, Alessandra Quota, Massimiliano Sacco, Calogera Gerardi, Luciana Rigoli, Lorella Pitrolo, Aurelio MaggioAbstract:In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are Deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus Deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value = 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the Deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the Deferoxamine treatment (P-value = 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of Deferoxamine, suggesting that this drug is an alternative option in cases in which Deferoxamine and deferasirox are contraindicated. Am. J. Hematol. 90:634–638, 2015. © 2015 Wiley Periodicals, Inc.
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deferiprone versus Deferoxamine in thalassemia intermedia results from a 5 year long term italian multicenter randomized clinical trial
American Journal of Hematology, 2015Co-Authors: Giuseppina Calvaruso, Angela Vitrano, Rosario Di Maggio, Grazia Colletta, Alessandra Quota, Massimiliano Sacco, Calogera Gerardi, Luciana Rigoli, Eliana Lai, Lorella PitroloAbstract:In patients with thalassemia intermedia (TI), such as beta-TI, alpha-thalassemia (mainly HbH disease and mild/moderate forms of HbE/beta-thalassemia), iron overload is an important challenge in terms of diagnosis, monitoring, and treatment. Moreover, to date, the only possible chelators available are Deferoxamine, deferasirox, and deferiprone. Here, we report the first 5-year long-term randomized clinical trial comparing the effectiveness of deferiprone versus Deferoxamine in patients with TI. Body iron burden, which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model (GLMM), showed a linear decrease over time in the mean serum ferritin levels in both treatment groups (P-value = 0.035). The overall period of observation was 235.2 person-years for the deferiprone patients compared with 214.3 person-years for the Deferoxamine patients. The results of the log-rank test suggested that the deferiprone treatment did not affect survival compared with the Deferoxamine treatment (P-value = 0.360). The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia. Neutropenia and agranulocytosis were also detected, suggesting needing of strict hematological control. In conclusion, long-term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of Deferoxamine, suggesting that this drug is an alternative option in cases in which Deferoxamine and deferasirox are contraindicated.
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improving survival with deferiprone treatment in patients with thalassemia major a prospective multicenter randomised clinical trial under the auspices of the italian society for thalassemia and hemoglobinopathies
Blood Cells Molecules and Diseases, 2009Co-Authors: Aurelio Maggio, Angela Vitrano, Marcello Capra, Liana Cuccia, Francesco Gagliardotto, Aldo Filosa, Carmelo Magnano, Michele Rizzo, Vincenzo Caruso, Calogera GerardiAbstract:Abstract The prognosis for thalassemia major has dramatically improved in the last two decades. However, many transfusion-dependent patients continue to develop progressive accumulation of iron. This can lead to tissue damage and eventually death, particularly from cardiac disease. Previous studies that investigated iron chelation treatments, including retrospective and prospective non-randomised clinical trials, suggested that mortality, due mainly to cardiac damage, was reduced or completely absent in patients treated with deferiprone (DFP) alone or a combined deferiprone–Deferoxamine (DFP–DFO) chelation treatment. However, no survival analysis has been reported for a long-term randomised control trial. Here, we performed a multicenter, long-term, randomised control trial that compared Deferoxamine (DFO) versus DFP alone, sequential DFP–DFO, or combined DFP–DFO iron chelation treatments. The trial included 265 patients with thalassemia major, with 128 (48.3%) females and 137 (51.7%) males. No deaths occurred with the DFP-alone or the combined DFP–DFO treatments. One death occurred due to graft versus host disease (GVHD) in a patient that had undergone bone marrow transplantation; this patient was censored at the time of transplant. Only one death occurred with the DFP–DFO sequential treatment in a patient that had experienced an episode of heart failure one year earlier. Ten deaths occurred with the Deferoxamine treatment. The main factors that correlated with an increase in the hazard ratio for death were: cirrhosis, arrhythmia, previous episode of heart failure, diabetes, hypogonadism, and hypothyroidism. In a Cox regression model, the interaction effect of sex and age was statistically significant ( p -value p -value In conclusion, the results of this study show that the risk factors for predicting mortality in patients with thalassemia major are Deferoxamine-treatment, complications, and the interaction effect of sex and age.
