Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study

Leukemia Research

Volumn 34, Issue 9, 2010, Pages 1143-1150

  Gattermann, Norbert ^a   Finelli, Carlo ^b   Della Porta, Matteo ^c   Fenaux, Pierre ^d   Ganser, Arnold ^e   Guerci Bresler, Agnes ^f   Schmid, Mathias ^g   Taylor, Kerry ^h   Vassilieff, Dominique ⁱ   Habr, Dany ^j   Domokos, Gabor ^j   Roubert, Bernard ^j   Rose, Christian ^k   Agaoglu, L ^l   Alimena, G ^m   Alonso, D ⁿ   Ame, S ^o   Angelucci, E ^p   Arrizabalaga, B ^q   Athanasiou Metaxa, M ^r   Augustson, B ^s   Aydinok, Y ^t   Baba, A ^u   Baccarani, M ^v   Beck, J ^w   Beris, P ^x   Beyne Rauzy, O ^y   Birgens, H ^z   Bordessoule, D ^aa   Borgna Pignatti, C ^ab   Bosly, A ^ac   Bouabdallah, K ^ad   Bowden, D ^ae   Bowen, D ^af   Bron, D ^ag   Cappellini, M D ^ah   Capra, M ^ai   Cartron, G ^aj   Cazzola, M ^ak   Chalkias, C ^al   Chan, L L ^am   Chancharunee, S ^an   Chapman, C ^ao   Charoenkwan, P ^ap   Chasapopoulou, E ^aq   Cheze, S ^ar   Chuansumrit, A ^an   Cianciulli, P ^as   Dauriac, C ^at   Delforge, M ^au   Dolken G ^av   Dombret, H ^aw   Duyster, J ^ax   Economopoulos, T ^ay   Ehninger, G ^az   Elalfy, M ^ba   El Beshlawy, A ^bb   Enggaard, L ^bc   Fillet, G ^bd   Filosa, A ^be   Forni, G ^bf   Galanello, R ^bg   Gastl, G ^bh   Giraudier, S ^bi   Goldfarb, A ^bj   Grigg, A ^bk   Gumruk, F ^bl   Ha, S Y ^bm   Haase, D ^bn   Heinrich, B ^bo   Hertzberg, M ^bp   Ho, J ^bq   Hsu, H C ^br   Huang, S ^bs   Hunault Berger, M ^bt   Inusa, B ^bu   Jaulmes, D ^bv   Jensen, J ^bw   Kattamis, A ^bx   Kilinc, Y ^by   Kim, K H ^bz   Kinsey, S ^ca   Kjeldsen, L ^cb   Koren, A ^cc   Lai, M E ^bg   Lai, Y ^cd   Lee, J W ^ce   Lee, K H ^cf   Lee, S H ^cg   Legros, L ^ch   Li, C ^ci   Li, C K ^cj   Li, Q ^ck   Lin, K H ^cl   Linkesch, W ^cm   Lubbert M ^cn   Lutz, D ^co   Mohamed Thalha, A J ^cp   Mufti, G ^cq   Muus, P ^cr   Nobile, F ^cs   Papadopoulos, N ^r   Perrotta, S ^ct   Petrini, M ^cu   Pfeilstocker M ^cv   Piga, A ^cw   Poole, J ^cx   Porter, J B ^cy   Pungolino, E ^ah   Quarta, G ^cz   Ravoet, C ^da   Jolimont Lobbes, H H ^da   Remacha, A F ^db   Roy, L ^dc   Saglio, G ^dd   Sanz, G ^de   Schmugge, M ^df   Schots, H ^dg   Secchi, G ^dh   Seymour, J F ^di   Shah, F ^dj   Shah, H ^dk   Shen, Z ^dl   Slama, B ^dm   Sutcharitchan, P ^dn   Taher, A ^do   Tamary, H ^dp   Tesch, H J ^dq   Thein, S L ^cq   Troncy, J ^dr   Villegas, A ^ds   Viprakasit, V ^dt   Wainwright, L ^du   Wassmann, B ^dv   Wettervald, M ^dw   Will, A ^dx   Wormann B ^dy   Wright, J ^dz   Yeh, S P ^ea   Yoon, S S ^eb   Zoumbos, N C ^ec   Zweegman, S ^ed   more..

^a HEINRICH HEINE UNIVERSITY   (Germany)

^b UNIVERSITY OF BOLOGNA   (Italy)

^c UNIVERSITY OF PAVIA   (Italy)

^d AVICENNE HOSPITAL   (France)

^e HANNOVER MEDICAL SCHOOL   (Germany)

^f CHU NANCY BRABOIS   (France)

^g UNIVERSITY HOSPITAL ULM   (Germany)

^h MATER ADULT HOSPITAL   (Australia)

ⁱ Paris 5 University ^*  (France)

^j NOVARTIS PHARMA AG   (Switzerland)

^k Hopital Saint Vincent de Paul GHICL   (France)

^l ISTANBUL UNIVERSITY   (Turkey)

^m POLICLINICO UMBERTO I   (Italy)

ⁿ HOSPITAL UNIVERSITARIO VIRGEN DEL ROCÍO   (Spain)

^o HÔPITAL DE HAUTEPIERRE   (France)

^p Ospedale Oncologico A Businco   (Italy)

^q HOSPITAL DE CRUCES   (Spain)

^r ARISTOTLE UNIVERSITY OF THESSALONIKI   (Greece)

^s SIR CHARLES GAIRDNER HOSPITAL   (Australia)

^t EGE UNIVERSITY   (Turkey)

^u HOSPITAL UNIVERSITI SAINS MALAYSIA   (Malaysia)

^v Az Ospedaliera di Bologna   (Italy)

^w UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^x GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^y CHU PURPAN   (France)

^z Amtssygehusetl Herlev   (Denmark)

^aa LIMOGES UNIVERSITY HOSPITAL   (France)

^ab UNIVERSITY HOSPITAL OF FERRARA   (Italy)

^ac UNIVERSITY HOSPITAL OF MONT GODINNE   (Belgium)

^ad BORDEAUX UNIVERSITY HOSPITAL   (France)

^ae MONASH MEDICAL CENTRE   (Australia)

^af LEEDS GENERAL INFIRMARY   (United Kingdom)

^ag JULES BORDET INSTITUTE   (Belgium)

^ah UNIVERSITY OF MILAN   (Italy)

^ai Ospedale Civico M Ascoli   (Italy)

^aj Clinique Victor Hugo   (France)

^ak FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^al GENERAL HOSPITAL OF LARISSA   (Greece)

^am UNIVERSITY MALAYA MEDICAL CENTRE   (Malaysia)

^an MAHIDOL UNIVERSITY   (Thailand)

^ao LEICESTER ROYAL INFIRMARY   (United Kingdom)

^ap CHIANG MAI UNIVERSITY   (Thailand)

^aq AHEPA UNIVERSITY HOSPITAL   (Greece)

^ar CHU Clemenceau   (France)

^as S EUGENIO HOSPITAL   (Italy)

^at PONTCHAILLOU UNIVERSITY HOSPITAL   (France)

^au UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^av UNIVERSITY OF GREIFSWALD   (Germany)

^aw SAINT LOUIS HOSPITAL   (France)

^ax TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^ay UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^az UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^ba AIN SHAMS UNIVERSITY   (Egypt)

^bb CAIRO UNIVERSITY   (Egypt)

^bc HILLERØD HOSPITAL   (Denmark)

^bd CHU SART TILMAN   (Belgium)

^be CARDARELLI HOSPITAL   (Italy)

^bf GALLIERA HOSPITAL   (Italy)

^bg Osp Regionale per le Microcitemie   (Italy)

^bh INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^bi HENRI MONDOR HOSPITAL   (France)

^bj HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^bk ROYAL MELBOURNE HOSPITAL   (Australia)

^bl HACETTEPE UNIVERSITY   (Turkey)

^bm QUEEN MARY HOSPITAL   (Hong Kong)

^bn UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^bo Gemeinschaftspraxis Brudler Heinrich   (Germany)

^bp WESTMEAD HOSPITAL   (Australia)

^bq ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^br TAIPEI VETERANS GENERAL HOSPITAL   (Taiwan)

^bs Guang Zhou Zhong Shan No2 Hospital   (China)

^bt ANGERS UNIVERSITY HOSPITAL   (France)

^bu EVELINA LONDON CHILDREN S HOSPITAL   (United Kingdom)

^bv HÔPITAL SAINT ANTOINE   (France)

^bw AARHUS UNIVERSITY HOSPITAL   (Denmark)

^bx UNIVERSITY OF ATHENS   (Greece)

^by CUKUROVA UNIVERSITY   (Turkey)

^bz Samsung Medical Center   (South Korea)

^ca ST JAMES S UNIVERSITY HOSPITAL   (United Kingdom)

^cb Rigshospitalet   (Denmark)

^cc HAEMEK MEDICAL CENTER   (Israel)

^cd NANJING MEDICAL UNIVERSITY   (China)

^ce The Catholic University of Korea   (South Korea)

^cf Asan Medical Center   (South Korea)

^cg ROYAL ADELAIDE HOSPITAL   (Australia)

^ch CENTRE HOSPITALIER UNIVERSITAIRE DE NICE   (France)

^ci FIRST MILITARY MEDICAL UNIVERSITY   (China)

^cj CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^ck Shanghai No1 People's Hospital   (China)

^cl NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^cm UNIVERSITY HOSPITAL GRAZ   (Austria)

^cn UNIVERSITY OF FREIBURG   (Germany)

^co A Ö Krankenhausder Elisabethinen   (Austria)

^cp UNIVERSITI KEBANGSAAN MALAYSIA MEDICAL CENTER   (Malaysia)

^cq KING S COLLEGE HOSPITAL   (United Kingdom)

^cr RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^cs BIANCHI MELACRINO MORELLI HOSPITAL   (Italy)

^ct UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^cu Ospedali Riuniti S Chiara   (Italy)

^cv HANUSCH HOSPITAL   (Austria)

^cw REGINA MARGHERITA CHILDREN S HOSPITAL   (Italy)

^cx UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^cy UNIVERSITY COLLEGE LONDON   (United Kingdom)

^cz Ospedale A Perrino   (Italy)

^da Universitàdegli Studidi Milano ^*

^db Hospitaldela SantaCreuiSantPau   (Spain)

^dc CENTRE JEAN BERNARD   (France)

^dd SAN LUIGI GONZAGA HOSPITAL   (Italy)

^de HOSPITAL UNIVERSITARIO LA FE   (Spain)

^df UNIVERSITY CHILDREN S HOSPITAL   (Switzerland)

^dg GHENT UNIVERSITY HOSPITAL   (Belgium)

^dh SS Annunziata Hospital   (Italy)

^di PETER MACCALLUM CANCER CENTRE   (Australia)

^dj WHITTINGTON HOSPITAL   (United Kingdom)

^dk HOSPITAL KUALA LUMPUR   (Malaysia)

^dl SHANGHAI SECOND MEDICAL UNIVERSITY   (China)

^dm CENTRE HOSPITALIER D AVIGNON   (France)

^dn CHULALONGKORN UNIVERSITY   (Thailand)

^do AMERICAN UNIVERSITY OF BEIRUT   (Lebanon)

^dp SCHNEIDER CHILDREN S MEDICAL CENTER OF ISRAEL   (Israel)

^dq Onkologische Gemeinschaftspraxis   (Germany)

^dr EDOUARD HERRIOT HOSPITAL   (France)

^ds HOSPITAL CLÍNICO SAN CARLOS   (Spain)

^dt MAHIDOL UNIVERSITY   (Thailand)

^du UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^dv GOETHE UNIVERSITY   (Germany)

^dw Dunkerque Hospital   (France)

^dx Manchester Children's Hospital   (United Kingdom)

^dy KLINIKUM BRAUNSCHWEIG   (Germany)

^dz ROYAL HALLAMSHIRE HOSPITAL   (United Kingdom)

^ea CHINA MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^eb Seoul National University Hospital   (South Korea)

^ec UNIVERSITY OF PATRAS   (Greece)

^ed VU UNIVERSITY MEDICAL CENTER   (Netherlands)

more..

Author keywords

Deferasirox; Iron chelation therapy; Labile plasma iron; Myelodysplastic syndromes; Serum ferritin

Indexed keywords

ALANINE AMINOTRANSFERASE; DEFERASIROX; FERRITIN; IRON;

ABDOMINAL PAIN; ADOLESCENT; ADULT; AGED; ANEMIA; ARTICLE; CHELATION THERAPY; CHILD; CLINICAL TRIAL; COLITIS; CONSTIPATION; CREATININE BLOOD LEVEL; CYTOPENIA; DEMENTIA; DIARRHEA; DOSE RESPONSE; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FATALITY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG WITHDRAWAL; DUODENITIS; ERYTHROCYTE TRANSFUSION; ESOPHAGITIS; FEMALE; FERRITIN BLOOD LEVEL; FEVER; GASTRITIS; GASTROINTESTINAL SYMPTOM; HEARING IMPAIRMENT; HEART FAILURE; HUMAN; HYPERTHERMIA; IRON BLOOD LEVEL; IRON INTAKE; IRON OVERLOAD; LEUKOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; MYELODYSPLASTIC SYNDROME; NEUTROPENIA; PANCYTOPENIA; PRESCHOOL CHILD; PRIORITY JOURNAL; PROSPECTIVE STUDY; RASH; SCHOOL CHILD; SIDE EFFECT; THROMBOCYTOPENIA; UPPER ABDOMINAL PAIN; VOMITING; WEIGHT REDUCTION;

EID: 77955268192     PISSN: 01452126     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.leukres.2010.03.009     Document Type: Article

References (28)

1. Andrews N.C. Disorders of iron metabolism. N Engl J Med 1999, 341:1986-1995.
2. Goldberg S.L., Chen E., Corral M., Guo A., Laouri M. Influence of RBC transfusions on clinical outcomes among USA Medicare beneficiaries with newly diagnosed myelodysplastic syndromes. Leuk Res 2009, 33(Suppl. 1):S116. [Abstract P099].
3. Sanz G., Nomdedeu B., Such E., Bernal T., Belkaid M., Ardanaz T., et al. Independent impact of iron overload and transfusion dependency on survival and leukemic evolution in patients with myelodysplastic syndrome. Blood 2008, 112(11). [Abstract 640].
4. Rose C, Brechignac S, Vassilief D, Pascal L, Stamatoullas A, Guerci-Bresler A, et al. Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A multicenter study by the GFM. Leuk Res 2010; [Epub ahead of print].
5. Bennett J.M. Consensus statement on iron overload in myelodysplastic syndromes. Am J Hematol 2008, 83:858-861.
6. Gattermann N. Iron overload in myelodysplastic syndromes. Hematol Oncol Clin N Am 2005, 19(Suppl. 1):1-26.
7. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology v.1: Myelodysplastic Syndromes; 2009. Available at: http://www.nccn.org/professionals/physician_gls/pdf/mds.pdf.
8. Jaeger M., Aul C., Sohngen D., Germing U., Schneider W. Iron overload in polytransfused patients with MDS: use of L1 for oral iron chelation. Drugs of Today 1992, 28(Suppl. A):143-147.
9. Jensen P.D., Heickendorff L., Pedersen B., Bendix-Hansen K., Jensen F.T., Christensen T., et al. The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload. Br J Haematol 1996, 94:288-299.
10. Jensen P.D., Jensen F.T., Christensen T., Nielsen J.L., Ellegaard J. Relationship between hepatocellular injury and transfusional iron overload prior to and during iron chelation with desferrioxamine: a study in adult patients with acquired anemias. Blood 2003, 101:91-96.
11. Kersten M.J., Lange R., Smeets M.E., Vreugdenhil G., Roozendaal K.J., Lameijer W., et al. Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. Ann Hematol 1996, 73:247-252.
12. Porter J., Galanello R., Saglio G., Neufeld E.J., Vichinsky E., Cappellini M.D., et al. Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study. Eur J Haematol 2008, 80:168-176.
13. Metzgeroth G., Dinter D., Schultheis B., Dorn-Beineke A., Lutz K., Leismann O., et al. Deferasirox in MDS patients with transfusion-caused iron overload-a phase-II study. Ann Hematol 2009, 88:301-310.
14. Wimazal F., Nosslinger T., Baumgartner C., Sperr W.R., Pfeilstocker M., Valent P. Deferasirox induces regression of iron overload in patients with myelodysplastic syndromes. Eur J Clin Invest 2009, 39:406-411.
15. Min Y., Cheong J., Kim H., Lee K., Yoon S., Lee J., et al. A multi-center, open label study evaluating the efficacy of iron chelation therapy with deferasirox in transfusional iron overload patients with myelodysplastic syndromes or aplastic anemia using quantitative R2 MRI. Leuk Res 2009, 33(Suppl. 1):S118-S119. [Abstract P102].
16. ®) therapy in a cohort of patients with MDS. Leuk Res 2009, 33(Suppl. 1):S120. [Abstract P104].
17. ®) improves iron burden in patients with myelodysplastic syndromes (MDS). Blood 2008, 112(11). [Abstract 634].
18. Ghoti H., Fibach E, Merkel D, Perez-Avraham G, Grisariu S, Rachmilewitz EA. Changes in parameters of oxidative stress and free iron biomarkers during treatment with deferasirox in iron-overloaded patients with myelodysplastic syndromes. Haematologica 2010; [Epub ahead of print].
19. ®) in 1744 patients with various transfusion-dependent anemias. Haematologica 2010, 95:557-566.
20. Esposito B.P., Breuer W., Sirankapracha P., Pootrakul P., Hershko C., Cabantchik Z.I. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood 2003, 102:2670-2677.
21. Cabantchik Z.I., Breuer W., Zanninelli G., Cianciulli P. LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol 2005, 18:277-287.
22. Brissot P, Deugnier Y, Cianciulli P, Cairo H, Jeng M, Rabault B. Dose dependent reductions in serum transaminases and ferritin levels correlate during long-term therapy with deferasirox (Exjade, ICL670). In: Book of abstracts. International BioIron Society; 2007; [Abstract 105].
23. Jones D.P., Carlson J.L., Mody V.C., Cai J., Lynn M.J., Sternberg P. Redox state of glutathione in human plasma. Free Radic Biol Med 2000, 28:625-635.
24. Fibach E., Rachmilewitz E. The role of oxidative stress in hemolytic anemia. Curr Mol Med 2008, 8:609-619.
25. Ghoti H., Amer J., Winder A., Rachmilewitz E., Fibach E. Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndrome. Eur J Haematol 2007, 79:463-467.
26. Olivieri N.F., Nathan D.G., MacMillan J.H., Wayne A.S., Liu P.P., McGee A., et al. Survival in medically treated patients with homozygous b-thalassemia. N Engl J Med 1994, 331:574-578.
27. Olivieri N.F., Brittenham G.M. Iron-chelating therapy and the treatment of thalassemia. Blood 1997, 89:739-761.
28. ®) in myelodysplastic syndromes (MDS) and non-MDS patients with transfusional iron overload: a pooled analysis focusing on renal function. Blood 2009, 114(22). [Abstract 1768].