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


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.
Walter
Patrick B
PB
Children's Hospital & Research Center Oakland, 747 52nd Street, Oakland, CA 94609, USA.
Macklin
Eric A
EA
Porter
John
J
Evans
Patricia
P
Kwiatkowski
Janet L
JL
Neufeld
Ellis J
EJ
Coates
Thomas
T
Giardina
Patricia J
PJ
Vichinsky
Elliott
E
Olivieri
Nancy
N
Alberti
Daniele
D
Holland
Jaymes
J
Harmatz
Paul
P
D000293:Adolescent; D000328:Adult; D001205:Ascorbic Acid / Q000378:metabolism; D001565:Benzoates / Q000009:adverse effects / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D000077588:Deferasirox; D003676:Deferoxamine / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology*; D014810:Vitamin E / Q000378:metabolism; D017086:beta-Thalassemia / Q000188:drug therapy* / Q000473:pathology
D001565:Benzoates; D007502:Iron Chelating Agents; D016877:Oxidants; D014230:Triazoles; D014810:Vitamin E; D002097:C-Reactive Protein; D003676:Deferoxamine; D001205:Ascorbic Acid; D000077588:Deferasirox