Progression-free survival (PFS) of patients with lower-risk myelodysplastic syndromes (MDS) treated with red blood cell transfusions is usually reduced, but it is unclear whether transfusion dose density is an independent prognostic factor. The European MDS Registry collects prospective data at 6-monthly intervals from newly diagnosed lower-risk myelodysplastic syndromes patients in 16 European countries and Israel. Data on the transfusion dose density - the cumulative dose received at the end of each interval divided by the time since the beginning of the interval in which the first transfusion was received - were analyzed using proportional hazards regression with time-varying co-variates, with death and progression to higher-risk MDS/acute myeloid leukemia as events. Of the 1,267 patients included in the analyses, 317 died without progression; in 162 patients the disease had progressed. PFS was significantly associated with age, EQ-5D index, baseline World Health Organization classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with PFS (P<1×10-4): dose density had an increasing effect on hazard until a dose density of 3 units/16 weeks. The transfusion dose density effect continued to increase beyond 8 units/16 weeks after correction for the impact of treatment with erythropoiesis-stimulating agents, lenalidomide and/or iron chelators. In conclusion, the negative effect of transfusion treatment on PFS already occurs at transfusion densities below 3 units/16 weeks. This indicates that transfusion dependency, even at relatively low dose densities, may be considered as an indicator of inferior PFS. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

Center for Clinical Transfusion Research Sanquin Research Leiden the Netherlands

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

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

Department of Clinical Hematology Hospital da Luz Lisbon Portugal

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

Department of Haematology Aberdeen Royal Infirmary Aberdeen UK

Department of Hematology Aarhus University Hospital Aarhus Denmark

Department of Hematology Democritus University of Thrace Medical School University Hospital of Alexandroupolis Alexandroupolis Greece

Department of Hematology Hospital Universitario y Politécnico La Fe Valencia Spain

Department of Hematology Oncology and Clinical Immunology Universitatsklinik Düsseldorf Düsseldorf Germany

Department of Hematology Oncology and Internal Medicine Warsaw Medical University Warsaw Poland

Department of Hematology Oncology Fondazione IRCCS 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 UK

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

Service de Médecine Interne IUCT Oncopole CHU Toulouse Toulouse France

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

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A predictive algorithm using clinical and laboratory parameters may assist in ruling out and in diagnosing MDS

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

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ClinicalTrials.gov
NCT00600860