Desferrioxamine treatment reduces blood transfusion requirements in patients with myelodysplastic syndrome

Jensen, Peter D. Ørberg; Jensen, I.; Ellegaard, J.

doi:10.1016/0145-2126(91)90455-3

Cited by 16 publications

(24 citation statements)

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“…Some reports in recent years have described a hematopoiesis improvement under highly effective chelation therapy almost exclusively with deferioxamine. 16,17 More recently, a similar effect was observed also during deferasirox treatment within only a few months of therapy.…”

Section: Discussionmentioning

confidence: 48%

“…[12][13][14] The effect seems to be shared by different diseases, including both MDS and primary myelofibrosis, but has never been observed in thalassemia patients. There are very few reports of similar effects with other iron chelators: 15,16 In 1996, Jensen et al described a hemoglobin improvement, but in some cases there were even trilinear responses in 11 MDS patients treated with deferioxamine for up to 60 months. 17 It has also been reported that myelofibrotic patients have a similar response to deferiprone.…”

Section: Introductionmentioning

confidence: 99%

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Deferasirox is a powerful NF- B inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging

Messa¹,

Carturan²,

Maffè³

et al. 2010

Haematologica

122

115

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BackgroundUsefulness of iron chelation therapy in myelodysplastic patients is still under debate but many authors suggest its possible role in improving survival of low-risk myelodysplastic patients. Several reports have described an unexpected effect of iron chelators, such as an improvement in hemoglobin levels, in patients affected by myelodysplastic syndromes. Furthermore, the novel chelator deferasirox induces a similar improvement more rapidly. Nuclear factor-κB is a key regulator of many cellular processes and its impaired activity has been described in different myeloid malignancies including myelodysplastic syndromes. Design and MethodsWe evaluated deferasirox activity on nuclear factor-κB in myelodysplastic syndromes as a possible mechanism involved in hemoglobin improvement during in vivo treatment. Forty peripheral blood samples collected from myelodysplastic syndrome patients were incubated with 50 μM deferasirox for 18h. ResultsNuclear factor-κB activity dramatically decreased in samples showing high basal activity as well as in cell lines, whereas no similar behavior was observed with other iron chelators despite a similar reduction in reactive oxygen species levels. Additionally, ferric hydroxyquinoline incubation did not decrease deferasirox activity in K562 cells suggesting the mechanism of action of the drug is independent from cell iron deprivation by chelation. Finally, incubation with both etoposide and deferasirox induced an increase in K562 apoptotic rate. ConclusionsNuclear factor-κB inhibition by deferasirox is not seen from other chelators and is iron and reactive oxygen species scavenging independent. This could explain the hemoglobin improvement after in vivo treatment, such that our hypothesis needs to be validated in further prospective studies.Key words: iron chelation therapy, nuclear factor-κB, myelodysplastic symdrome. Haematologica 2010;95(8):1308-1316. doi:10.3324/haematol.2009 Deferasirox is a powerful NF-κB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging Citation: Messa E, Carturan S, Maffè C, Pautasso M, Bracco E, Roetto A, Messa F, Arruga F, Defilippi I, Rosso V, Zanone C, Rotolo A, Greco E, Pellegrino RM, Alberti D, Saglio G, and Cilloni D. Deferasirox is a powerful NF-κB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging.

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Section: Discussionmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Deferasirox is a powerful NF- B inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging

Messa¹,

Carturan²,

Maffè³

et al. 2010

Haematologica

122

115

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“…[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%

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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“…Desferrioxamine (DFO) is of benefit for patients receiving a large amount of erythrocytes in preventing the accumulation of iron and the end organ damage caused by it. Jensen and coworkers recently suggested [10] that DFO treatment has a beneficial effect on erythropoiesis in patients with MDS. Moreover, it also increased platelet and granulocyte counts in these patients.…”

Section: Discussionmentioning

confidence: 99%

Pyridoxin‐responsive anaemia in a patient with a history of polycythaemia vera

vanGameren¹,

Wijnja²,

Louwes

et al. 1997

Journal of Internal Medicine

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). Pyridoxinresponsive anaemia in a patient with a history of polycythaemia vera (Case Report). J Intern Med 1997; 242: 79-81.Pancytopenia in the course of polycythaemia vera (PV) following the proliferative and stable phase, ultimately leads to a spent phase characterized by extensive marrow fibrosis. We describe a patient with a history of PV and pancytopenia caused by myelodysplasia, before a genuine end stage myelofibrosis had occurred. The related anaemia was responsive to pyridoxin.

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Desferrioxamine treatment reduces blood transfusion requirements in patients with myelodysplastic syndrome

Cited by 16 publications

References 0 publications

Deferasirox is a powerful NF- B inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging

Deferasirox is a powerful NF- B inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging

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

Pyridoxin‐responsive anaemia in a patient with a history of polycythaemia vera

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