Michel Delforge1, Dominik Selleslag2, Yves Beguin3, Agnès Triffet4, Philippe Mineur5, Koen Theunissen6, Carlos Graux7, Fabienne Trullemans8, Dominique Boulet9, Koen Van Eygen10, Lucien Noens11, Steven Van Steenweghen12, Jan Lemmens13, Pascal Pierre14, Randal D'hondt15, Augustin Ferrant16, Dries Deeren17, Ann Van De Velde18, Wim Wynendaele19, Marc André7, Robrecht De Bock20, André Efira21, Dimitri Breems22, Anne Deweweire23, Kurt Geldhof24, Wim Pluymers25, Amanda Harrington26, Karen MacDonald27, Ivo Abraham28, Christophe Ravoet29. 1. Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium. 2. Algemeen Ziekenhuis Sint-Jan, Brugge, Belgium. 3. Centre Hospitalier Universitaire de Liège and Université de Liège, Liège, Belgium. 4. Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium. 5. Grand Hôpital de Charleroi, Charleroi, Belgium. 6. Jessa Ziekenhuis, Hasselt, Belgium. 7. Cliniques Universitaires UCL de Mont-Godinne, Mont-Godinne, Belgium. 8. Universitair Ziekenhuis Brussel, Brussel, Belgium. 9. Centre Hospitalier Régional Clinique St. Joseph, Mons, Belgium. 10. Algemeen Ziekenhuis Groeninge, Kortrijk, Belgium. 11. Universitair Ziekenhuis Gent, Gent, Belgium. 12. Centre Hospitalier Régional de la Citadelle, Liège, Belgium. 13. Algemeen Ziekenhuis St-Augustinus, Wilrijk, Belgium. 14. Clinique du Sud Luxembourg, Arlon, Belgium. 15. Algemeen Ziekenhuis Damiaan, Oostende, Belgium. 16. Cliniques Universitaires UCL St. Luc, Woluwe, Belgium. 17. Heilig Hart Ziekenhuis, Roeselare, Belgium. 18. Universitair Ziekenhuis Antwerpen, Edegem, Belgium. 19. Algemeen Ziekenhuis Imelda, Bonheiden, Belgium. 20. Ziekenhuis Netwerk Antwerpen Middelheim, Antwerpen, Belgium. 21. Centre Hospitalier Universitaire Brugmann, Bruxelles, Belgium. 22. Ziekenhuis Netwerk Antwerpen Stuivenberg, Antwerpen, Belgium. 23. Réseau Hospitalier de Médecine Sociale Baudour, Baudour, Belgium. 24. Jan Yperman Ziekenhuis, Ieper, Belgium. 25. Novartis Pharma, Vilvoorde, Belgium. 26. Matrix45, Tucson, AZ, USA; Center for Health Outcomes and Pharmacoeconomic Research, University of Arizona, Tucson, AZ, USA. 27. Matrix45, Tucson, AZ, USA. 28. Matrix45, Tucson, AZ, USA; Center for Health Outcomes and Pharmacoeconomic Research, University of Arizona, Tucson, AZ, USA. Electronic address: iabraham@matrix45.com. 29. Centre Hospitalier de Jolimont, Jolimont, Belgium; Institut Jules Bordet, Bruxelles, Belgium.
Abstract
BACKGROUND: Most patients with myelodysplastic syndromes (MDS) require transfusions at the risk of iron overload and associated organ damage, and death. Emerging evidence indicates that iron chelation therapy (ICT) could reduce mortality and improve survival in transfusion-dependent MDS patients, especially those classified as International Prognostic Scoring System (IPSS) Low or Intermediate-1 (Low/Int-1). METHODS: Follow-up of a retrospective study. Sample included 127 Low/Int-1 MDS patients from 28 centers in Belgium. Statistical analysis stratified by duration (≥6 versus <6 months) and quality of chelation (adequate versus weak). RESULTS: Crude chelation rate was 63% but 88% among patients with serum ferritin ≥1000 μg/L. Of the 80 chelated patients, 70% were chelated adequately mainly with deferasirox (26%) or deferasirox following deferoxamine (39%). Mortality was 70% among non-chelated, 40% among chelated, 32% among patients chelated ≥6 m, and 30% among patients chelated adequately; with a trend toward reduced cardiac mortality in chelated patients. Overall, median overall survival (OS) was 10.2 years for chelated and 3.1 years for non-chelated patients (p<0.001). For patients chelated ≥6 m or patients classified as adequately chelated, median OS was 10.5 years. Mortality increased as a function of average monthly transfusion intensity (HR=1.08, p=0.04) but was lower in patients receiving adequate chelation or chelation ≥6 m (HR=0.24, p<0.001). CONCLUSION: Six or more months of adequate ICT is associated with markedly better overall survival. This suggests a possible survival benefit of ICT in transfusion-dependent patients with lower-risk MDS.
BACKGROUND: Most patients with myelodysplastic syndromes (MDS) require transfusions at the risk of iron overload and associated organ damage, and death. Emerging evidence indicates that iron chelation therapy (ICT) could reduce mortality and improve survival in transfusion-dependent MDSpatients, especially those classified as International Prognostic Scoring System (IPSS) Low or Intermediate-1 (Low/Int-1). METHODS: Follow-up of a retrospective study. Sample included 127 Low/Int-1MDSpatients from 28 centers in Belgium. Statistical analysis stratified by duration (≥6 versus <6 months) and quality of chelation (adequate versus weak). RESULTS: Crude chelation rate was 63% but 88% among patients with serum ferritin ≥1000 μg/L. Of the 80 chelated patients, 70% were chelated adequately mainly with deferasirox (26%) or deferasirox following deferoxamine (39%). Mortality was 70% among non-chelated, 40% among chelated, 32% among patients chelated ≥6 m, and 30% among patients chelated adequately; with a trend toward reduced cardiac mortality in chelated patients. Overall, median overall survival (OS) was 10.2 years for chelated and 3.1 years for non-chelated patients (p<0.001). For patients chelated ≥6 m or patients classified as adequately chelated, median OS was 10.5 years. Mortality increased as a function of average monthly transfusion intensity (HR=1.08, p=0.04) but was lower in patients receiving adequate chelation or chelation ≥6 m (HR=0.24, p<0.001). CONCLUSION: Six or more months of adequate ICT is associated with markedly better overall survival. This suggests a possible survival benefit of ICT in transfusion-dependent patients with lower-risk MDS.
Authors: Amer M Zeidan; Franklin Hendrick; Erika Friedmann; Maria R Baer; Steven D Gore; Medha Sasane; Carole Paley; Amy J Davidoff Journal: J Comp Eff Res Date: 2015-08 Impact factor: 1.744
Authors: Zhantao Yang; Siobán B Keel; Akiko Shimamura; Li Liu; Aaron T Gerds; Henry Y Li; Brent L Wood; Bart L Scott; Janis L Abkowitz Journal: Sci Transl Med Date: 2016-05-11 Impact factor: 17.956
Authors: Naser Mobarra; Mehrnoosh Shanaki; Hassan Ehteram; Hajar Nasiri; Mehdi Sahmani; Mohsen Saeidi; Mehdi Goudarzi; Hoda Pourkarim; Mehdi Azad Journal: Int J Hematol Oncol Stem Cell Res Date: 2016-10-01