Iron overload due to red blood cell (RBC) transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome (MDS) patients. Many studies have suggested improved survival after iron chelation therapy (ICT), but valid data are limited. The aim of this study was to assess the effect of ICT on overall survival and hematologic improvement in lower-risk MDS patients in the European MDS registry. We compared chelated patients with a contemporary, non-chelated control group within the European MDS registry, that met the eligibility criteria for starting iron chelation. A Cox proportional hazards model was used to assess overall survival (OS), treating receipt of chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2,200 patients, 224 received iron chelation. The hazard ratio and 95% confidence interval for OS for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative RBC transfusions, Revised-International Prognostic Scoring System (IPSS-R), and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, RBC transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R, and, in addition, corrected for cumulative RBC transfusions and presence of ringed sideroblasts, demonstrated a significantly improved OS for chelated patients with a hazard ratio of 0.42 (0.27-0.63) compared to non-chelated patients. Up to 39% of chelated patients reached an erythroid response. In conclusion, our results suggest that iron chelation may improve OS and hematopoiesis in transfused lower-risk MDS patients. This trial was registered at clinicaltrials.gov identifier: 00600860.

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

Centre for Clinical Transfusion Research Sanquin Research Leiden the Netherlands

Clinic of Hematology Clinical Center of Vojvodina Faculty of Medicine University of Novi Sad Novi Sad Serbia

Department of Clinical Epidemiology Leiden University Medical Center Leiden the Netherlands

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

Department of Haematology Aarhus University Hospital Aarhus Denmark

Department of Haematology Aberdeen Royal Infirmary Aberdeen UK

Department of Haematology Hospital Universitario y Politécnico La Fe Valencia Spain

Department of Haematology Oncology and Clinical Immunology Universitätsklinik Düsseldorf Düsseldorf Germany

Department of Haematology Oncology and Internal Medicine Warszawa Medical University Warszawa Poland

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

Department of Hematology Hospital da Luz Lisbon Portugal

Department of Hematology Oncology Fondazione Istituto Di Ricovero e Cura a Carettere Scientifico Policlinico San Matteo University of Pavia Pavia Italy

Department of Hematology Radboud University Medical Center Nijmegen the Netherlands

Department of Internal Medicine 5 Innsbruck Medical University Innsbruck Austria

Department of Internal Medicine Division of Hematology Merkur University Hospital Zagreb Croatia

Department of Medicine A Tel Aviv Sourasky Medical Center and Sackler Medical Faculty Tel Aviv University Tel Aviv Israel

Department of Medicine Division of Hematology Karolinska Institutet Stockholm Sweden

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

Department of Tumor Immunology Nijmegen Center for Molecular Life Sciences Radboud University Medical Center Nijmegen the Netherlands

Epidemiology and Cancer Statistics Group Department of Health Sciences University of York York USA

Service d'Hématologie Centre Hospitalier Universitaire Brabois Vandoeuvre Nancy France

Service d'Hématologie Hôpital Saint Louis Assistance Publique des Hôpitaux de Paris and Université Paris 7 Paris France

St James's Institute of Oncology Leeds Teaching Hospitals Leeds UK

Unit Transfusion Medicine Sanquin Blood Bank Amsterdam the Netherlands

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