Red blood cell transfusions remain one of the cornerstones in supportive care of lower-risk patients with myelodysplastic syndromes. We hypothesized that patients develop oxidant-mediated tissue injury through the formation of toxic iron species, caused either by red blood cell transfusions or by ineffective erythropoiesis. We analyzed serum samples from 100 lower-risk patients with myelodysplastic syndromes at six-month intervals for transferrin saturation, hepcidin-25, growth differentiation factor 15, soluble transferrin receptor, non-transferrin bound iron and labile plasma iron in order to evaluate temporal changes in iron metabolism and the presence of potentially toxic iron species and their impact on survival. Hepcidin levels were low in 34 patients with ringed sideroblasts compared to 66 patients without. Increases of hepcidin and non-transferrin bound iron levels were visible early in follow-up of all transfusion-dependent patient groups. Hepcidin levels significantly decreased over time in transfusion-independent patients with ringed sideroblasts. Increased soluble transferrin receptor levels in transfusion-independent patients with ringed sideroblasts confirmed the presence of ineffective erythropoiesis and suppression of hepcidin production in these patients. Detectable labile plasma iron levels in combination with high transferrin saturation levels occurred almost exclusively in patients with ringed sideroblasts and all transfusion-dependent patient groups. Detectable labile plasma iron levels in transfusion-dependent patients without ringed sideroblasts were associated with decreased survival. In conclusion, toxic iron species occurred in all transfusion-dependent patients and in transfusion-independent patients with ringed sideroblasts. Labile plasma iron appeared to be a clinically relevant measure for potential iron toxicity and a prognostic factor for survival in transfusion-dependent patients. clinicaltrials.gov Identifier: 00600860.

Center of Hematology and Bone Marrow Transplantation Fundeni Clinical Institute Bucharest Romania

Department of Clinical Hematology Institute of Hematology and Blood Transfusion Prague Czech Republic

Department of Haematology Aberdeen Royal Infirmary UK

Department of Haematology Airedale NHS trust UK

Department of Haematology Blackpool Victoria Hospital Lancashire UK

Department of Hematology Cancer Center Amsterdam VU University Medical Center The Netherlands

Department of Hematology Laikon General Hospital National and Kapodistrian University of Athens Greece

Department of Hematology Radboud university medical center Nijmegen the Netherlands

Department of Hematology University Medical Centre Groningen the Netherlands

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Masaryk University Czech Republic

Department of Laboratory Medicine Hepcidinanalysis com and Radboudumc expertise center for iron disorders Radboud university medical center Nijmegen the Netherlands and

Department of Medicine Division of Hematology Karolinska Institutet Stockholm Sweden

Department of Medicine Division of Hematology University of Patras Medical School Greece

Department of Medicine Section of Hematology and Coagulation Sahlgrenska University Hospital Göteborg Sweden

Epidemiology and Cancer Statistics Group University of York UK

Nijmegen Center for Molecular Life Sciences Department of Tumor Immunology Radboud university medical center the Netherlands

St James's Institute of Oncology Leeds Teaching Hospitals UK

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Toxic iron species in lower-risk myelodysplastic syndrome patients: course of disease and effects on outcome

Novel dynamic outcome indicators and clinical endpoints in myelodysplastic syndrome; the European LeukemiaNet MDS Registry and MDS-RIGHT project perspective

Impact of treatment with iron chelation therapy in patients with lower-risk myelodysplastic syndromes participating in the European MDS registry

Impact of red blood cell transfusion dose density on progression-free survival in patients with lower-risk myelodysplastic syndromes

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ClinicalTrials.gov
NCT00600860