OJBD  Vol.1 No.1 , September 2011
Is Iron-Chelation Therapy Useful in Persons with Myelodysplastic Syndrome Receive?
Abstract: Iron overload in myelodysplastic syndrome (MDS) results from multiple RBC-transfusions and inappropriate increased iron absoption associated with ineffective erythropoiesis. Data from hereditary iron-loading anemias indicate long-term consequences of iron toxicity are preventable and potentially reversible by effective iron-chelation therapy (ICT). There is increasing interest in using ICT in persons with MDS because of the recent introduction of orally effective iron-chelators which are suitable for older persons, (1-4). Ideally, evidence supporting the benefit of ICT in MDS should be evidenced-based, especially data from randomized trials showing better survival and, in exceptional cases, improved heart function . Such data are lacking. Nevertheless, it is possible to rely on the extensive data from trials of ICT in persons with thalassemia and to use well-defined predictors of increased risks of life-threatening complications to identify persons with MDS most likely to benefit from iron-chelating therapy.
Cite this paper: nullC. Hershko and R. Gale, "Is Iron-Chelation Therapy Useful in Persons with Myelodysplastic Syndrome Receive?," Open Journal of Blood Diseases, Vol. 1 No. 1, 2011, pp. 3-7. doi: 10.4236/ojbd.2011.11002.

[1]   N. Gattermann, “The Treatment of Secondary Hemoch-romatosis,” Deutsch Arzteblatt International, Vol. 106, No. 30, 2009, pp. 499-504. doi: 10.3238/arztebl.2009.0499

[2]   G. Metzgeroth, D. Dinter, B. Schultheis, et al., “Defera-sirox in MDS Patients with Transfusion-Caused Iron Overload—A Phase-II Study,” Annals Hematology, Vol. 88, No. 4, 2009, pp. 301-310. doi:10.1007/s00277-008-0588-3

[3]   P. Fenaux and C. Rose, “Impact of Iron Overload in Myelodysplastic Syndromes,” Blood Reviews, Vol.23 Suppl. 1, 2009, pp. S15-S19. doi:10.1016/S0268-960X(09)70005-0

[4]   L. Malcovati, “Red Blood Cell Transfusion Therapy and Iron Chelation in Patients with Myelodysplastic Syn-dromes,” Clinical Lymphoma Myeloma & Leukemia, Vol. 9, Suppl. 3, 2009, pp. S305-S311.

[5]   J. M. Bennett, “MDS Foundation’s Working Group on Transfusional Iron Overload. Consensus Statement on Iron Overload in Myelodysplastic Syndromes,” American Journal Hematology, Vol. 83, No.11, 2008, pp. 858-861. doi:10.1002/ajh.21269

[6]   L. M. Buja, W. C. Roberts, “Iron in the Heart. Etiology and Clinical Significance,” American Journal Medicine, Vol. 51, No. 2, 1971, pp. 209-221. doi:10.1016/0002-9343(71)90240-3

[7]   A. I. Schafer, R. G. Cheron, R. Dluhy, et al., “Clinical Consequences of Acquired Transfusional Iron Overload in Adults, The New England Journal Medicine, Vol. 304, No. 6, 1981, pp. 319-324. doi:10.1056/NEJM198102053040603

[8]   P. D. Jensen, F. T. Jensen, T Christensen, et al., “Evaluation of Myocardial Iron by Magnetic Resonance Imaging during Iron Chelation Therapy with Deferrio- xamine: Indication of Close Relation between Myocardial iron Content and Chelatable Iron Pool,” Blood, Vol. 101, No. 11, 2003, pp. 4632-4639.

[9]   A. A. Di Tucci, G. Matta, S. Deplano, et al., “Myocardial Iron Overload Assessment by T2* Magnetic Resonance Imaging in Adult Transfusion Dependent Patients with Acquired Anemias,” Haematologica, Vol. 93, No. 9, 2008, pp. 1385-1388. [10] J. Chacko, D. J. Pennell, M. A. Tanner, et al., “Myocardial Iron Loading by Magnetic Resonance Imaging T2* in Good Prognostic Myelodysplastic Syndrome Patients on Long-Term Blood Transfusions,” British Journal Hae-matology, Vol. 138, No. 5, 2007, pp. 587-593. doi:10.1111

[10]   Y. Matzner, A. M. Konijn and C. Hershko, “Serum Ferri-tin in Hematologic Malignancies,” American Journal Hematology, Vol. 9, No. 1, 1980, pp. 13-22. doi:10.1002/ajh.2830090103

[11]   M. H. Lee and R. T. Means Jr, “Extremely Elevated Serum Ferritin Levels in a University Hospital: Associated Diseases and Clinical Significance,” American Journal Medicine, Vol. 98, No. 6, 1995, pp. 566-571. doi:10.1016/S0002-9343(99)80015-1

[12]   A. Tefferi and J. W. Vardiman, “Myelodysplastic Syn-dromes,” The New England Journal Medicine, Vol. 361, No. 19, 2009, pp. 1872-1885. doi:10.1056/NEJMra0902908

[13]   C. Hershko, “Oral Iron Chelators: New Opportunities and New Dilemmas,” Haematologica, Vol. 91, No. 10, 2006, 1307-1312.

[14]   G. Zanninelli, W. Breuer and Z. I. Cabancthik, “Daily Labile Plasma Iron as an Indicator of Chelator Activity in Thalassaemia Major Patients,” British Journal Haema-tology, Vol. 147, No. 5, 2009, pp. 744-751. doi:10.1111/j.1365-2141.2009.07907.x

[15]   A. Raptis, M. S. Duh, S. T. Wang, et al., “Treatment of Transfusional Iron Overload in Patients with Myelodys-plastic Syndrome or Severe Anemia: Data from Multi-center Clinical Practices,” Transfusion, Vol. 50, No. 1, 2010, pp. 190-199.

[16]   H. A. Leitch, J. M. Chase, T. A. Goodman, et al., “Im-proved Survival in Red Blood Cell Transfusion Dependent Patients with Primary Myelofibrosis (PMF) Receiving Iron Chelation Therapy,” Journal of Hematology Oncology, Vol. 28, No. 1, 2009, pp. 40-48.

[17]   C. Rose, S. Brechignac, D. Vassilief, et al., “GFM (Groupe Francophone des Myélodysplasies).Does Iron Chelation Therapy Improve Survival in Regularly Trans-fused Lower Risk MDS Patients? A Multicenter Study by the GFM,” Leukemia Research, Vol. 34, No. 7, 2010, pp. 864-870. doi:10.1016/j.leukres.2009.12.004

[18]   P. D. Jensen, I. M. Jensen and J. Ellegaard, “Desferriox-amine Treatment Reduces Blood Transfusion Require-ments in Patients with Myelodysplastic Syndrome,” British Journal Haematology, Vol. 80, No. 1, 1992, pp. 121-124.

[19]   E. Messa, D. Cilloni, F. Messa, et al., “Deferasirox Treatment Improved the Hemoglobin Level and Decreased Transfusion Requirements in Four Patients with the Myelodysplastic Syndrome and Primary Myelofibrosis,” Acta Haematologia, Vol. 120, No. 2, 2008, pp. 70-74.

[20]   C. Camaschella, A. Campanella, L. De Falco, et al., “The Human Counterpart of Zebrafish Shiraz Shows Siderob-lastic-Like Microcytic Anemia and Iron Overload,” Blood, Vol. 110, No. 4, 2007, pp. 1353-1358.

[21]   V. Pullarkat, “Objectives of Iron Chelation Therapy in Myelodysplastic Syndromes: More than Meets the Eye?” Blood, Vol. 114, No. 26, 2009, pp. 5251-5255.

[22]   J. Koreth, J. H. Antin, “Iron Overload in Hematologic Malignancies and Outcome of Allogeneic Hematopoietic Stem Cell Transplantation,” Haematologica, Vol. 95, No. 3, 2010, pp. 364-366.

[23]   C. E. Cooper, G. R. Lynagh, K. P. Hoyes, et al., “The Relationship of Intracellular Iron Chelation to the Inhibition and Regeneration of Human Ribonucleotide Reductase,” The Journal of Biological Chemistry, Vol. 271, No. 34, 1996, pp. 20291-20299. doi:10.1074/jbc.271.34.20291

[24]   E. Angelucci, G M. Brittenham, C. E. McLaren, et al., “Hepatic Iron Concentration and Total Body Iron Stores in Thalassemia Major,” The New England Journal Medicine, Vol. 343, No. 5, 2000, pp. 327-331. doi:10.1056/NEJM200008033430503