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RED score and hepcidin:ferritin in lower-risk MDS
which in turns induces proliferation of these cells and pos- sible improvement of anemia.30 An ongoing clinical trial is investing the use of low-dose deferasirox in anemic patients with lower-risk MDS who have failed to respond to treatment with ESA (ClinicalTrials.gov identifier: NCT03387475). Secondly, increasing hepcidin level could prevent further accumulation of iron and reduce iron- mediated tissue injury by redistributing iron from parenchymal tissues to macrophages where iron is less toxic. A clinical trial with an agonist of hepcidin (LJPC- 410) is ongoing in patients with b-thalassemia with myocardial iron overload (ClinicalTrials.gov identifier: NCT03381833). In patients with dysregulated iron home- ostasis, hepcidin agonists or low-dose deferasirox could be considered in combination with ESA.
Concerning the RED score, the data are consistent with those of other flow cytometry scores described by the European LeukemiaNet predicting a lower response to ESA or hypomethylating agents in MDS patients.31-33 Flow cytometry techniques have been recommended by inter- national expert panels for use in the diagnosis of MDS, particularly in order to measure dyserythropoiesis objec- tively.14,34 A French national survey on the practical use of flow cytometry in the diagnosis of MDS showed that about 12 of the 50 French centers that routinely perform
flow cytometry for the diagnosis of myeloid neoplasms use flow cytometry for the diagnosis of MDS and only four centers use the RED score (Orianne Wagner-Ballon, personal communication). However, if other larger studies confirm the usefulness of the RED score in the prediction of response to ESA, these techniques will be used more often in a practical way.
To conclude, in our series, the flow cytometry RED score and hepcidin:ferritin ratio enabled identification of patients who would not respond to ESA, and GDF-15 lev- els and hepcidin:ferritin ratio predicted shorter duration of response. These results warrant confirmation in larger series. In patients with MDS, other treatments aimed at restoring redox and iron homeostasis could efficiently improve the erythroid response.
Acknowledgments
This study received the support of a research grant from Hospira/Pfizer and the institutional support of Assistance Publique-Hôpitaux de Paris through the Unité de Recherche Clinique Paris Descartes Necker Cochin. The authors thank all investigators of the Groupe Francophone des Myélodysplasies (GFM) and Audrey Gauthier for technical assistance. We wish to pay tribute to Christian Rose who died recently. He was an active member of the GFM and a leader in the field of iron chelation.
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