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Cited by 87Hemoglobinopathies and Related DisordersIron Metabolism and DisordersAntioxidant Activity and Oxidative Stress

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Inflammation and oxidant-stress in -thalassemia patients treated with iron chelators deferasirox (ICL670) or deferoxamine: an ancillary study of the Novartis CICL670A0107 trial

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Walter, P. B., Macklin, E. A., Porter, J., Evans, P., Kwiatkowski, J. L., Neufeld, E. J., Coates, T., Giardina, P. J., Vichinsky, E., Olivieri, N., Alberti, D., Holland, J., Harmatz, P., for the Thalassemia Clinical Research Network·2008·Haematologica
DOI 10.3324/haematol.11755
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Abstract

BACKGROUND: We assessed whether oxidant-stress and inflammation in beta-thalassemia could be controlled by the novel oral iron chelator deferasirox as effectively as by deferoxamine. DESIGN AND METHODS: Forty-nine subjects were enrolled from seven sites and studied at baseline, and after 1, 6, and 12 months of therapy. Malondialdehyde, protein carbonyls, vitamins E and C, total non-transferrin bound iron, transferrin saturation, C-reactive protein, cytokines, serum ferritin concentration and liver iron concentration were measured. RESULTS: Liver iron concentration and ferritin declined significantly in both treatment groups during the study. This paralleled a significant decline in the oxidative-stress marker malondialdehyde (deferasirox -22%/year, deferoxamine -28%/year, average decline p=0.006). The rates of decline did not differ between treatment groups. Malondialdehyde was higher in both treatment groups than in a group of 30 non-thalassemic controls (p < 0.001). The inflammatory marker high-sensitivity C-reactive protein decreased significantly only in the group receiving deferasirox (deferasirox -51%/year, deferoxamine +8.5%/year, p = 0.02). This result was confounded by a chance difference in the level of high-sensitivity C-reactive protein between the two groups at baseline, but analyses controlling for this difference suggested an equally large treatment effect. CONCLUSIONS: Iron chelation therapy with deferoxamine or with deferasirox was equally effective in decreasing iron burden and malondialdehyde. The possible differential effect of the two chelators on inflammation warrants further investigation.

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  • Infections and inflammations are more frequent in thalassemic patients with iron overload induced by frequent blood transfusions.

    “Infections and inflammations are more frequent in thalassemic patients with iron overload induced by frequent blood transfusions [104].”

    From The utility of iron chelators in the management of inflammatory disorders (2015) · cites this paper as [104]

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Metadata

Authors
Walter, P. B., Macklin, E. A., Porter, J., Evans, P., Kwiatkowski, J. L., Neufeld, E. J., Coates, T., Giardina, P. J., Vichinsky, E., Olivieri, N., Alberti, D., Holland, J., Harmatz, P., & for the Thalassemia Clinical Research Network
Affiliations
  • New England Research Institutes (US)
  • Massachusetts General Hospital (US)
  • Children's Hospital of Philadelphia (US)
  • Boston Children's Hospital (US)
  • Children's Hospital Los Angeles (US)
  • NewYork–Presbyterian Hospital (US)
  • University Health Network (CA)
  • Novartis (United States) (US)
Corresponding author
Harmatz, P.
ORCID
Venue
Haematologica
Publisher
Ferrata Storti Foundation (Haematologica)
Published
2008-06-01
Volume
93
Issue
6
Pages
817-825
ISSN
  • 0390-6078 (ISSN-L)
  • 1592-8721
DOI
10.3324/haematol.11755
OpenAlex
W2125610771
Cited by
87
References
2
Citations by year
2026: 4 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 8 · 2014: 7 · 2013: 8 · 2012: 6
FWCI
2.61
Type
journal article
Language
en
Open access
Locations
  • Haematologica (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Children's Hospital of Philadelphia
  • New England Research Institutes
  • University College London
  • Translational Cancer Research Network
  • National Institutes of Health (5u01hl065260-10, 5r01dk057778-07)
  • National Heart, Lung, and Blood Institute (U01-HL-65244, U01-HL-65238, U01-HL65233, U01HL065232, U01-HL-65239, U01-HL65232, U01HL065244, U01-HL-65260, U01HL065238, U01-HL065260, U01HL065233, U01HL065239)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK57778)
  • National Center for Research Resources (M01-RR02172, M01 RR 01271, M01RR001271, UL1RR024134, M01RR002172)
Topics
  • Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords
beta-thalassemia, deferasirox, deferoxamine, iron chelation therapy, oxidative stress, inflammation, malondialdehyde, C-reactive protein, liver iron concentration, serum ferritin, iron overload
MeSH terms
Deferasirox, Adolescent, Adult, Ascorbic Acid, Benzoates, C-Reactive Protein, Child, Deferoxamine, Female, Humans, Iron Chelating Agents, Male, Triazoles, Vitamin E, Lipid Peroxidation, Oxidants, beta-Thalassemia, Oxidative Stress

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