The Effect of Oral Iron Chelator Deferiprone on Iron Overload and Oxidative Stress in Patients with Myelodysplastic Syndromes: A Study by the Israeli MDS Working Group.

Autor:	Merkel D; Chaim Sheba Medical Center, Tel Hashomer, Israel.; School of Medicine, Tel Aviv University, Tel Aviv, Israel., Soffer S; School of Medicine, Tel Aviv University, Tel Aviv, Israel., Filanovsky K; Kaplan Medical Center, Rehovot, Israel.; Hadassah Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel., Braester A; Galilee Medical Center, Faculty of Medicine, 'AZRIELI', Bar-Ilan University, Nahariya, Israel., Fibach E; Hadassah Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel., Dana M; Hadassah Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel., Ofran Y; Hadassah Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.; Shaare Zedek Medical Center, Jerusalem, Israel., Greenbaum U; Soroka Medical Center, Beer Sheba, Israel.; Ben-Gurion University, Beer Sheba, Israel., Nagler A; Chaim Sheba Medical Center, Tel Hashomer, Israel.; School of Medicine, Tel Aviv University, Tel Aviv, Israel., Amitai I; Chaim Sheba Medical Center, Tel Hashomer, Israel, irinayoav@gmail.com.; School of Medicine, Tel Aviv University, Tel Aviv, Israel, irinayoav@gmail.com., Mittelman M; School of Medicine, Tel Aviv University, Tel Aviv, Israel.; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Jazyk:	angličtina
Zdroj:	Acta haematologica [Acta Haematol] 2024; Vol. 147 (4), pp. 427-434. Date of Electronic Publication: 2023 Dec 16.
DOI:	10.1159/000535749
Abstrakt:	Background: Most patients with lower risk myelodysplastic neoplasms or syndromes (MDSs) 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 MDSs. Methods: Adult lower risk MDS patients with a cumulative transfusion burden of >20 red blood cell 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 and 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 grades 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. (© 2023 The Author(s). Published by S. Karger AG, Basel.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu