The Effect of The Oral Iron Chelator Deferiprone on Iron Overload and Oxidative Stress in Patients with Myelodysplastic Syndromes A Study by the Israeli MDS Working Group
The Author(s). Published by S. Karger AG, Basel..
BACKGROUND: Most patients with lower risk myelodysplastic neoplasms (MDS) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-chelation therapy is applied to attenuate the toxic effects of this state. Deferiprone (DFP) is an oral iron chelator, which is not commonly used in this patient population, due to safety concerns, mainly agranulocytosis. The purpose of this study was to assess the effect of DFP, on oxidative stress parameters in iron overloaded RBC transfusion-dependent patients with lower risk MDS.
METHODS: Adult lower-risk MDS patients with a cumulative transfusion burden of >20 red blood cells units and evidence of iron overload (serum ferritin >1,000 ng/mL) were included in this study. DFP was administered (100 mg/kg/day) for 4 months. Blood samples for oxidative stress parameters and iron overload parameters were done at baseline and monthly: reactive oxygen species (ROS), phosphatidylserine, reduced glutathione, membrane lipid peroxidation, serum ferritin and cellular labile iron pool. The primary efficacy variable was ROS. Tolerability and side-effects were recorded as well. A paired t-test was applied for statistical analyses.
RESULTS: Eighteen patients were treated with DFP. ROS significantly decreased in all cell lineages: median decrease of 58.6% in RBC, 33.3% in PMN, and 39.8% in platelets (p<0.01 for all). Other oxidative stress markers improved: phosphatidylserine decreased by 57.95%, lipid peroxidase decreased by 141.3%, and reduced gluthathione increased by 72.8% (p<0.01 for all). The iron-overload marker, cellular labile iron pool, decreased by 35% in RBCs, 44.3% in PMN, and 46.3% in platelets (p<0.01 for all). No significant changes were observed in SF levels. There were no events of agranulocytosis. All AEs were grade 1-2.
CONCLUSIONS: Herein we showed preliminary evidence that DFP decreases iron-induced oxidative stress in MDS patients with a good tolerability profile (albeit a short follow-up period). No cases of severe neutropenia or agranulocytosis were reported. The future challenge is to prove that reduction in iron toxicity will eventually be translated into a clinically meaningful improvement.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Acta haematologica - (2023) vom: 16. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Merkel, Drorit [VerfasserIn] |
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| Links: |
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| Themen: |
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| Anmerkungen: |
Date Revised 17.12.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1159/000535749 |
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| funding: |
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NLM365952281 |
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| 245 | 1 | 4 | |a The Effect of The Oral Iron Chelator Deferiprone on Iron Overload and Oxidative Stress in Patients with Myelodysplastic Syndromes A Study by the Israeli MDS Working Group |
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| 520 | |a The Author(s). Published by S. Karger AG, Basel. | ||
| 520 | |a BACKGROUND: Most patients with lower risk myelodysplastic neoplasms (MDS) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-chelation therapy is applied to attenuate the toxic effects of this state. Deferiprone (DFP) is an oral iron chelator, which is not commonly used in this patient population, due to safety concerns, mainly agranulocytosis. The purpose of this study was to assess the effect of DFP, on oxidative stress parameters in iron overloaded RBC transfusion-dependent patients with lower risk MDS | ||
| 520 | |a METHODS: Adult lower-risk MDS patients with a cumulative transfusion burden of >20 red blood cells units and evidence of iron overload (serum ferritin >1,000 ng/mL) were included in this study. DFP was administered (100 mg/kg/day) for 4 months. Blood samples for oxidative stress parameters and iron overload parameters were done at baseline and monthly: reactive oxygen species (ROS), phosphatidylserine, reduced glutathione, membrane lipid peroxidation, serum ferritin and cellular labile iron pool. The primary efficacy variable was ROS. Tolerability and side-effects were recorded as well. A paired t-test was applied for statistical analyses | ||
| 520 | |a RESULTS: Eighteen patients were treated with DFP. ROS significantly decreased in all cell lineages: median decrease of 58.6% in RBC, 33.3% in PMN, and 39.8% in platelets (p<0.01 for all). Other oxidative stress markers improved: phosphatidylserine decreased by 57.95%, lipid peroxidase decreased by 141.3%, and reduced gluthathione increased by 72.8% (p<0.01 for all). The iron-overload marker, cellular labile iron pool, decreased by 35% in RBCs, 44.3% in PMN, and 46.3% in platelets (p<0.01 for all). No significant changes were observed in SF levels. There were no events of agranulocytosis. All AEs were grade 1-2 | ||
| 520 | |a CONCLUSIONS: Herein we showed preliminary evidence that DFP decreases iron-induced oxidative stress in MDS patients with a good tolerability profile (albeit a short follow-up period). No cases of severe neutropenia or agranulocytosis were reported. The future challenge is to prove that reduction in iron toxicity will eventually be translated into a clinically meaningful improvement | ||
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| 700 | 1 | |a Filanovsky, Kalman |e verfasserin |4 aut | |
| 700 | 1 | |a Braester, Andrei |e verfasserin |4 aut | |
| 700 | 1 | |a Fibach, Eitan |e verfasserin |4 aut | |
| 700 | 1 | |a Dana, Mutaz |e verfasserin |4 aut | |
| 700 | 1 | |a Ofran, Yishai |e verfasserin |4 aut | |
| 700 | 1 | |a Greenbaum, Uri |e verfasserin |4 aut | |
| 700 | 1 | |a Nagler, Arnon |e verfasserin |4 aut | |
| 700 | 1 | |a Amitai, Irina |e verfasserin |4 aut | |
| 700 | 1 | |a Mittelman, Moshe |e verfasserin |4 aut | |
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