Hematological improvement during iron-chelation therapy in myelodysplastic syndromes: The experience of the “Rete Ematologica Lombarda”

Molteni, Alfredo; Riva, Marta; Pellizzari, Annamaria; Borin, Lorenza; Freyre, Alessandra; Greco, Rosa; Ubezio, Marta; Bernardi, Massimo; Fariciotti, Alessio; Nador, Guido; Nichelatti, Michele; Ravano, Emanuele; Morra, Enrica

doi:10.1016/j.leukres.2013.07.006

Cited by 21 publications

(18 citation statements)

References 24 publications

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“…The resulting iron overload is a common complication of MDS management and is treated with iron chelators (Gattermann et al , ). Intriguingly, several retrospective (Molteni et al , ; Molica et al , ) and prospective (Gattermann, ; Gattermann et al , ; List et al , ; Angelucci et al , ) clinical reports have shown an additional positive effect of the iron chelator deferasirox (DFX) on haematopoiesis (reviewed in Guariglia et al , ), leading to a partial reduction or a complete interruption of transfusions in a limited but significant proportion (10–15%) of MDS patients. Of note, none of the reported studies focused on the haematological response as end‐point.…”

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confidence: 99%

The iron chelator deferasirox affects redox signalling in haematopoietic stem/progenitor cells

et al. 2015

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The iron chelator deferasirox (DFX) prevents complications related to transfusional iron overload in several haematological disorders characterized by marrow failure. It is also able to induce haematological responses in a percentage of treated patients, particularly in those affected by myelodysplastic syndromes. The underlying mechanisms responsible for this feature, however, are still poorly understood. In this study, we investigated the effect of DFX-treatment in human haematopoietic/progenitor stem cells, focussing on its impact on the redox balance, which proved to control the interplay between stemness maintenance, self-renewal and differentiation priming. Here we show, for the first time, that DFX treatment induces a significant diphenyleneiodonium-sensitive reactive oxygen species (ROS) production that leads to the activation of POU5F1 (OCT4), SOX2 and SOX17 gene expression, relevant in reprogramming processes, and the reduction of the haematopoietic regulatory proteins CTNNB1 (β-Catenin) and BMI1. These DFX-mediated events were accompanied by decreased CD34 expression, increased mitochondrial mass and up-regulation of the erythropoietic marker CD71 (TFRC) and were compound-specific, dissimilar to deferoxamine. Our findings would suggest a novel mechanism by which DFX, probably independently on its iron-chelating property but through ROS signalling activation, may influence key factors involved in self-renewal/differentiation of haematopoietic stem cells.

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confidence: 99%

The iron chelator deferasirox affects redox signalling in haematopoietic stem/progenitor cells

et al. 2015

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“…Hematologic improvement may also involve other lineages. [10][11][12][13] In the RYTHMEX study, we observed major HI-P and/or HI-N in half of patients treated at least 9 months with deferasirox, therefore suggesting an effect of deferasirox on non-erythroid response. Although time to hematologic improvement observed in our study was particularly late (6 months and 10 months for HI-N and HI-P, respectively), it has to be noted that, although more rarely, hematologic improvement may occur early, 11 even in the setting of higher risk patients.…”

Section: Changes In Serum Ferritin Levelsmentioning

confidence: 69%

Prospective evaluation of the effect of deferasirox on hematologic response in transfusion‐dependent patients with low‐risk MDS and iron overload

Rosé

Lenoir

Gyan

et al. 2018

European J of Haematology

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“…Several case descriptions 10,11 and published cohorts [12][13][14][15][16][17][18] have reported improved erythropoiesis and a decreased transfusion requirement in mds patients treated with iron chelation.…”

Section: Discussionmentioning

confidence: 98%

“…A recent retrospective cohort described outcomes for 53 patients with transfusion-dependent mds treated with deferasirox (n = 36) and deferoxamine (n = 17) 14 . The authors of that study reported that 19 patients (35.8%) experienced an erythroid response by International Working Group 2000 criteria 14,20 . Of those 19, 5 experienced a major erythroid response, with 3 becoming transfusion-independent; the remaining 14 experienced a minor erythroid response.…”

Section: Discussionmentioning

confidence: 99%

A Case of Transfusion Independence in a Patient with Myelodysplastic Syndrome Using Deferasirox, Sustained for Two Years after Stopping Therapy

Sanford

Hsia

2015

Current Oncology

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Patients with myelodysplastic syndrome (mds) experience clinical complications related to progressive marrow failure and have an increased risk of developing acute myeloid leukemia. Frequent red blood cell transfusion can lead to clinical iron overload and is associated with decreased survival in mds patients. Iron chelation therapy reduces markers of iron overload and prevents end-organ damage.Here, we present the case of a patient with lowrisk mds with transfusional iron overload. He was treated for 2 years with an oral iron chelator, deferasirox, and after 12 months of treatment, he experienced a hemoglobin increase of more than 50 g/L, becoming transfusion-independent. He has remained transfusion-independent, with a normal hemoglobin level, for more than 2 years since stopping chelation therapy. Hematologic and erythroid responses have previously been reported in mds patients treated with iron chelation. The durability of our patient’sresponse suggests that iron chelation might alter the natural history of mds in some patients.

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Hematological improvement during iron-chelation therapy in myelodysplastic syndromes: The experience of the “Rete Ematologica Lombarda”

Cited by 21 publications

References 24 publications

The iron chelator deferasirox affects redox signalling in haematopoietic stem/progenitor cells

The iron chelator deferasirox affects redox signalling in haematopoietic stem/progenitor cells

Prospective evaluation of the effect of deferasirox on hematologic response in transfusion‐dependent patients with low‐risk MDS and iron overload

A Case of Transfusion Independence in a Patient with Myelodysplastic Syndrome Using Deferasirox, Sustained for Two Years after Stopping Therapy

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