Changes in parameters of oxidative stress and free iron biomarkers during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndromes

Ghoti, Hussam; Fibach, Eitan; Merkel, Drorit; Perez-Avraham, Galit; Grisariu, Sigal; Rachmilewitz, Eliezer A.

doi:10.3324/haematol.2010.024992

Cited by 77 publications

(56 citation statements)

References 12 publications

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“…In addition to direct iron accumulation, labile plasma iron (LPI), non-transferrin-bound iron (NTBI) and reactive oxygen species (ROS) appear to play an important role in the pathogenesis of ironrelated organ damage in patients with IO [22,32,[37][38][39][40][41][42]. DFX therapy leads to sustained and rapid reductions in levels of LPI, NTBI and ROS within 3 months of initiation of DFX therapy [21][22][23][24]43] …”

Section: Discussionmentioning

confidence: 99%

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

et al. 2015

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Aims: Iron overload adversely affects patients with myelodysplastic syndromes (MDS), but benefits of iron chelation therapy have not been clearly demonstrated. We examined the association between deferasirox (DFX) therapy and mortality in transfusion-receiving Medicare patients. Patients & methods: MDS patients from 2005 to 2008 were identified using ICD-9 codes from 100% Medicare claims. Patients receiving ≥20 blood units were observed until death or end of study. Marginal structural models were used for estimation. Results: 3926 patients (10.1% used DFX) were observed for a mean of 48.8 weeks. Each incremental week of DFX was associated with a significant reduction in mortality risk (hazard ratio [HR]: 0.989; 95% CI: 0.983-0.996; p = 0.001). Conclusion: DFX therapy is associated with a reduced mortality risk among older MDS patients who received a minimum transfusion threshold.

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Section: Discussionmentioning

confidence: 99%

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

et al. 2015

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“…21,[24][25][26] This hypothesis is supported by the ability of deferasirox to provide 24-hour sustained suppression of LPI 17 and to significantly reduce reactive oxygen species. 37 In vitro and in vivo data in leukemia cell lines and peripheral mononuclear cells collected from patients with MDS have demonstrated the inhibitory effects of deferasirox on nuclear factor-κB (NF-κB) activity. 38 This protein has been shown to be constitutively activated in bone marrow samples from patients with MDS, 39 and is involved in several cellular processes including cell proliferation and differentiation and suppression of apoptosis.…”

Section: Hematologic Response In Mdsmentioning

confidence: 99%

Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

et al. 2012

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BackgroundReductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on these reductions/improvements have been limited to case reports and small studies. Design and MethodsTo explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients' Iron Chelation with Exjade ® (EPIC) study using International Working Group 2006 criteria. ResultsTwo-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders. ConclusionsThis analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes.Key words: myelodysplastic syndromes, deferasirox, iron overload, iron chelation therapy, hematologic response. Haematologica 2012;97(9):1364-1371. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Gattermann N, Finelli C, Della Porta M, Fenaux P, Stadler M, Guerci-Bresler A, Schmid M, Taylor K, Vassilieff D, Habr D, Marcellari A, Roubert B, and Rose C. Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes. Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

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“…This hypothesis is supported by the ability of deferasirox to provide 24-h sustained suppression of labile plasma iron and to significantly reduce reactive oxygen species. 6 In vitro and in vivo data have demonstrated the inhibitory effects of deferasirox on Nuclear factor-kappa B activity. Alternative mechanisms may include redistribution of iron from storage sites to hematopoietic tissue, or an effect on the clone or on BM.…”

mentioning

confidence: 99%

Deferasirox improves hematopoiesis after allogeneic hematopoietic SCT

Visani

Guiducci

Giardini

et al. 2014

Bone Marrow Transplant

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Changes in parameters of oxidative stress and free iron biomarkers during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndromes

Cited by 77 publications

References 12 publications

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

Deferasirox improves hematopoiesis after allogeneic hematopoietic SCT

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