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

Drorit Merkel, Shelly Soffer, Kalman Filanovsky, Andrei Braester, Eitan Fibach, Mutaz Dana, Yishai Ofran, Uri Greenbaum, Arnon Nagler, Irina Amitai, Moshe Mittelman

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Most patients with lower risk myelodysplastic neoplasms or syndromes (MDSs) become RBC transfusiondependent, 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.

Original languageEnglish
JournalActa Haematologica
Early online date16 Dec 2023
DOIs
StateE-pub ahead of print - 16 Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s). Published by S. Karger AG, Basel.

Keywords

  • Deferiprone
  • Iron overload
  • Iron-chelation therapy
  • Myelodysplastic syndromes
  • Oxidative stress

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