Positive effects on hematopoiesis in patients with myelodysplastic syndrome receiving deferasirox as oral iron chelation therapy: A brief review

Guariglia, Roberto; Martorelli, Maria Carmen; Villani, Oreste; Pietrantuono, Giuseppe; Mansueto, Giovanna; D’Auria, Fiorella; Grieco, Vitina; Bianchino, Gabriella; Lerose, Rosa; Bochicchio, Giovanni Battista; Musto, Pellegrino

doi:10.1016/j.leukres.2010.11.027

Cited by 60 publications

(55 citation statements)

References 35 publications

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“…Reduction in oxidative stress, a state which has a variety of inhibitory effects on erythroid and hematopoietic function, 35 has been proposed as a possible explanation for the observed hematologic improvement. 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.…”

Section: Hematologic Response In Mdsmentioning

confidence: 93%

“…[6][7][8][9][10][11][12][13][14][15] In addition to reports of reduction in iron burden, 16,17 a number of recently published case reports and studies have reported improvements in hematologic parameters and transfusion requirements during iron chelation therapy with deferasirox. [17][18][19][20][21][22][23][24][25][26] There is also limited evidence of hematologic improvement in patients with MDS treated with deferoxamine, 27,28 although the exact mechanism of the hematologic response to iron chelators is unknown.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Hematologic Response In Mdsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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“…Recently, an oral iron chelator, deferasirox, was for the first time developed and is used for decreasing iron overload in the patients of transfusion-dependent anemic diseases with success (23,24). Here, we used deferasirox or intensive phlebotomy in rats, following intraperitoneal injection of crocidolite, to evaluate their effects on mesothelial carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Deferasirox Induces Mesenchymal–Epithelial Transition in Crocidolite-Induced Mesothelial Carcinogenesis in Rats

Nagai

Okazaki

Chew

et al. 2013

Cancer Prevention Research

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Asbestos was used worldwide in huge quantities in the past century. However, because of the unexpected carcinogenicity to mesothelial cells with an extremely long incubation period, many countries face this long-lasting social problem. Mesothelioma is often diagnosed in an advanced stage, for which no effective therapeutic protocols are yet established. We previously reported on the basis of animal experiments that the major pathology in asbestos-induced mesothelial carcinogenesis is local iron overload. Here, we undertook to find an effective strategy to prevent, delay, or lower the malignant potential of mesothelioma during asbestos-induced carcinogenesis. We used intraperitoneal injections of crocidolite to rats. We carried out a 16-week study to seek the maximal-tolerated intervention for iron reduction via oral deferasirox administration or intensive phlebotomy. Splenic iron deposition was significantly decreased with either method, and we found that Perls' iron staining in spleen is a good indicator for iron reduction. We injected a total of 10 mg crocidolite at the age of six weeks, and the preventive measures were via repeated oral administration of 25 to 50 mg/kg/d deferasirox or weekly to bimonthly phlebotomy of 4 to 10 mL/kg/d. The animals were observed until 110 weeks. Deferasirox administration significantly increased the fraction of less malignant epithelioid subtype. Although we found a slightly prolonged survival in deferasirox-treated female rats, larger sample size and refinement of the current protocol are necessary to deduce the cancer-preventive effects of deferasirox. Still, our results suggest deferasirox serves as a potential preventive strategy in people already exposed to asbestos via iron reduction. Cancer Prev Res; 6(11); 1222-30. Ó2013 AACR.

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“…Patients are affected by the inconvenient administration, which subsequently leads to lower adherence to the treatment and insufficient IC resulting in increased morbidity and mortality [5,6]. Interestingly, IC has been shown to improve hematopoiesis in some patients [11][12][13]. Although the exact mechanism is not clear yet improvement of hematopoiesis might be due to a reduction of oxidative stress in hematopoietic progenitors in general and erythropoietic progenitors in particular [10].…”

Section: Introductionmentioning

confidence: 99%

Updated recommendations on the management of gastrointestinal disturbances during iron chelation therapy with Deferasirox in transfusion dependent patients with myelodysplastic syndrome – Emphasis on optimized dosing schedules and new formulations

Nolte¹,

Angelucci²,

Breccia³

et al. 2015

Leukemia Research

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a b s t r a c tMyelodysplastic syndromes (MDS) are oligoclonal hematopoietic disorders characterized by peripheral cytopenias with anemias being the most prevalent feature. The majority of patients will depend on regular transfusions of packed red blood cells (PRBC) during the course of the disease. Particularly patients with MDS and low risk for transformation into acute myeloid leukemia and low risk of early death will receive PRBC transfusions on a regular basis, which puts them at high risk for transfusional iron overload. Transfusion dependence has been associated with negative impact on organ function and reduced life expectancy.Recently, several retrospective but also some prospective studies have indicated, that transfusion dependent patients with MDS might benefit from consequent iron chelation with regard to morbidity and mortality. However, low treatment adherence due to adverse events mainly gastrointestinal in nature is an important obstacle in achieving sufficient iron chelation in MDS patients. Here, we will summarize and discuss the existing data on Deferasirox in low risk MDS published so far and provide recommendations for optimal management of gastrointestinal adverse events during iron chelation aiming at improving treatment compliance and, hence, sufficiently removing excess iron from the patients.

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Positive effects on hematopoiesis in patients with myelodysplastic syndrome receiving deferasirox as oral iron chelation therapy: A brief review

Cited by 60 publications

References 35 publications

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

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

Deferasirox Induces Mesenchymal–Epithelial Transition in Crocidolite-Induced Mesothelial Carcinogenesis in Rats

Updated recommendations on the management of gastrointestinal disturbances during iron chelation therapy with Deferasirox in transfusion dependent patients with myelodysplastic syndrome – Emphasis on optimized dosing schedules and new formulations

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