Efficacy and safety of a novel combination of two oral chelators deferasirox/deferiprone over deferoxamine/deferiprone in severely iron overloaded young beta thalassemia major patients

European Journal of Haematology

Volumn 95, Issue 5, 2015, Pages 411-420

  Elalfy, Mohsen S ^a   Adly, Amira M ^a   Wali, Yasser ^b   Tony, Samir ^b   Samir, Ahmad ^a   Elhenawy, Yasmine I ^a  

^a AIN SHAMS UNIVERSITY   (Egypt)

^b SULTAN QABOOS UNIVERSITY HOSPITAL   (Oman)

Author keywords

Cardiac MRI; Combined oral iron chelators; Liver iron; Quality of life; Thalassemia major

Indexed keywords

AMINOTRANSFERASE; CREATININE; DEFERASIROX; DEFERIPRONE; DEFEROXAMINE; FERRITIN; IRON; BENZOIC ACID DERIVATIVE; IRON CHELATING AGENT; PYRIDONE DERIVATIVE; TRIAZOLE DERIVATIVE;

ABDOMINAL PAIN; ACUTE CHOLECYSTITIS; ADULT; AMINOTRANSFERASE BLOOD LEVEL; ARTHRALGIA; ARTICLE; CARDIOVASCULAR MAGNETIC RESONANCE; COMPARATIVE STUDY; CONCENTRATION (PARAMETERS); CONTINUOUS INFUSION; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DEMOGRAPHY; DISEASE SEVERITY; DRUG EFFICACY; DRUG SAFETY; ECHOCARDIOGRAPHY; ELECTROCARDIOGRAM; FEMALE; FERRITIN BLOOD LEVEL; HEMATOLOGICAL PARAMETERS; HUMAN; IRON CHELATION; IRON OVERLOAD; IRON RESTRICTION; LIVER IRON CONCENTRATION; MAJOR CLINICAL STUDY; MALE; MAXIMUM TOLERATED DOSE; MEDICATION COMPLIANCE; NAUSEA; NEUTROPENIA; NUCLEAR MAGNETIC RESONANCE IMAGING; PATIENT COMPLIANCE; PATIENT SATISFACTION; PRIORITY JOURNAL; PROSPECTIVE STUDY; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; RASH; SHORT FORM 36; THALASSEMIA MAJOR; THORAX RADIOGRAPHY; TREATMENT RESPONSE; ADOLESCENT; BETA-THALASSEMIA; CHILD; CLINICAL TRIAL; COMBINATION DRUG THERAPY; COMPLICATION; MULTICENTER STUDY; PRESCHOOL CHILD; SEVERITY OF ILLNESS INDEX;

ADOLESCENT; BENZOATES; BETA-THALASSEMIA; CHILD; CHILD, PRESCHOOL; DEFEROXAMINE; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; IRON CHELATING AGENTS; IRON OVERLOAD; MALE; PYRIDONES; SEVERITY OF ILLNESS INDEX; TRIAZOLES;

EID: 84940782881     PISSN: 09024441     EISSN: 16000609     Source Type: Journal    
DOI: 10.1111/ejh.12507     Document Type: Article

References (37)

1. Ladis V, Chouliaras G, Berdousi H, Kanavakis E, Kattamis C. Longitudinal study of survival and causes of death in patients with thalassemia major in Greece. Ann N Y Acad Sci 2005;1054:445-50.
2. Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004;89:1187-93.
3. Esposito BP, Breuer W, Sirankapracha P, Pootrakul P, Hershko C, Cabantchik ZI. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood 2003;102:2670-7.
4. Breuer W, Shvartsman M, Cabantchik Z. Intracellular labile iron. Int J Biochem Cell Biol 2008;40:350-4.
5. Porter JB. Deferoxamine pharmacokinetics. Semin Hematol 2001;38:63-8.
6. Cianciulli P. Iron chelation therapy in thalassemia syndromes. Mediterr J Hematol Infect Dis 2009;1:e2009034.
7. Cabantchik Z, Breuer W, Zanninelli G, Cianciulli P. LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol 2005;18:277-87.
8. Tanner MA, Galanello R, Dessi C, et al. A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance. Circulation 2007;115:1876-84.
9. Berdoukas V, Farmaki K, Carson S, Wood J, Coates T. Treating thalassemia major-related iron overload: the role of deferiprone. J Blood Med 2012;3:119-29.
10. Wood JC, Kang BP, Thompson A, Giardina P, Harmatz P, Glynos T, Paley C, Coates TD. The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores. Blood 2010;116:537-43.
11. Telfer PT, Prestcott E, Holden S, Walker M, Hoffbrand AV, Wonke B. Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. Br J Haematol 2000;110:971-7.
12. Motamed N, Ayatollahi AR, Zare N, Sadeghi-Hassanabadi A. Validity and reliability of the Persian translation of the SF-36 version 2 questionnaire. East Mediterr Health J 2005;11:349-57.
13. Rofail D, Abetz L, Viala M, Gait C, Baladi JF, Payne K. Satisfaction and adherence in patients with iron overload receiving iron chelation therapy as assessed by a newly developed patient instrument. Value Health 2009;12:109-17.
14. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN. Histological grading and staging of chronic hepatitis. J Hepatol 1995;22:696-9.
15. Pepe A, Lombardi M, Positano V, Cracolici E, Capra M, Malizia R, Prossomariti L, De Marchi D, Midiri M, Maggio A. Evaluation of the efficacy of oral deferiprone in beta-thalassemia major by multislicemultiecho T2*. Eur J Haematol 2006;76:183-92.
16. Davis B, Porter J. Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk β-thalassemia. Blood 2000;95:1229-36.
17. Taher A, Cappellini MD, Vichinsky E, Galanello R, Piga A, Lawniczek T, Clark J, Habr D, Porter JB. Efficacy and safety of deferasirox doses of >30 mg/kg per d in patients with transfusion-dependent anaemia and iron overload. Br J Haematol 2009;147:752-9.
18. Walter PB, Macklin EA, Porter J, et al.; Thalassemia Clinical Research Network. Inflammation and oxidant-stress in beta-thalassemia patients treated with iron chelators deferasirox (ICL670) or deferoxamine: an ancillary study of the Novartis CICL670A0107 trial. Haematologica 2008;93:817-25.
19. Poggiali E, Cassinerio E, Zanaboni L, Cappellini M. An update on iron chelation therapy. Blood Transfus 2012;10:411-22.
20. Farmaki K, Tzoumari I, Pappa C. Oral chelators in transfusion-dependent thalassemia major patients may prevent or reverse iron overload complications. Blood Cells Mol Dis 2011;47:33-40.
21. Glickstein H, El RB, Link G, Breuer W, Konijn AM, Hershko C, Nick H, Cabantchik ZI. Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences. Blood 2006;108:3195-203.
22. Hoffbrand V, Taher A, Cappellini D. How I treat transfusional iron overload. Blood 2012;120:3657-69.
23. Voskaridou E, Christoulas D, Terpos E. Successful chelation therapy with the combination of deferasirox and deferiprone in a patient with thalassaemia major and persisting severe iron overload after single-agent chelation therapies. Br J Haematol 2011;154:654-6.
24. Berdoukas V, Carson S, Nord A, Dongelyan A, Gavin S, Hofstra TC, Wood JC, Coates T. Combining two orally active iron chelators for thalassemia. Ann Hematol 2010;89:1177-8.
25. Balocco M, Carrara P, Pinto V, Forni GL. Daily alternating deferasirox and deferiprone therapy for "hard-to-chelate" beta-thalassemia major patients. Am J Hematol 2010;85:460-1.
26. Pennell DJ, Porter JB, Cappellini MD, et al. Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload. Haematologica 2011;96:48-54.
27. Taher A, Elalfy MS, Al ZK, Daar S, Al Jefri A, Habr D, Kriemler-Krahn U, El-Ali A, Roubert B, El-Beshlawy A. Importance of optimal dosing ≥30 mg/kg/d during deferasirox treatment: 2.7-yr follow-up from the ESCALATOR study in patients with β-thalassaemia. Eur J Haematol 2011;87:355-65.
28. Pennell DJ, Porter JB, Piga A, et al.; CORDELIA study investigators. A 1-year randomized controlled trial of deferasirox versus deferoxamine for myocardial iron removal in beta-thalassemia major (CORDELIA). Blood 2014;123:1447-54.
29. Aydinok Y, Ulger Z, Nart D, Terzi A, Cetiner N, Ellis G, Zimmermann A, Manz C. A randomized controlled 1-year study of daily deferiprone plus twice weekly desferrioxamine compared with daily deferiprone monotherapy in patients with thalassemia major. Haematologica 2007;92:1599-606.
30. Tavecchia L, Masera N, Russo P, Ciro A, Vincenzi A, Vimercati C, Masera G. Successful recovery of acute hemosiderotic heart failure in beta-thalassemia major treated with a combined regimen of desferrioxamine and deferiprone. Haematologica 2006;91:ECR19.
31. Evans P, Kayyali R, Hider RC, Eccleston J, Porter JB. Mechanisms for the shuttling of plasma non-transferrin-bound iron (NTBI) onto deferoxamine by deferiprone. Transl Res 2010;156:55-67.
32. Porter JB, Rafique R, Srichairatanakool S, Davis BA, Shah FT, Hair T, Evans P. Recent insights into interactions of deferoxamine with cellular and plasma iron pools: implications for clinical use. Ann N Y Acad Sci 2005;1054:155-68.
33. Roberts DJ, Brunskill SJ, Doree C, Williams S, Howard J, Hyde CJ. Oral deferiprone for iron chelation in people with thalassemia. Cochrane Database Syst Rev 2007;18:CD004839.
34. Porter J, Bowden DK, Economou M, et al. Health-related quality of life, treatment satisfaction, adherence and persistence in β-thalassemia and myelodysplastic syndrome patients with iron overload receiving deferasirox: results from the epic clinical trial. Anemia 2012;2012:297641.
35. Elalfy MS, Massoud W, Elsherif NH, Labib JH, Elalfy OM, Elaasar S, von Mackensen S. A new tool for the assessment of satisfaction with iron chelation therapy (ICT-Sat) for patients with β-thalassemia major. Pediatr Blood Cancer 2012;58:910-5.
36. Vichinsky E, Pakbaz Z, Onyekwere O, et al. Patient-reported outcomes of deferasirox (Exjade, ICL670) versus deferoxamine in sickle cell disease patients with transfusional hemosiderosis: substudy of a randomized open-label phase II trial. Acta Haematol 2008;119:133-41.
37. Elalfy M, Wali YA, Qari M, et al. Deviating from safety guidelines during deferiprone therapy in clinical practice may not be associated with higher risk of agranulocytosis. Pediatr Blood Cancer 2014;61:879-84.