Annals of Hematology

, Volume 85, Issue 5, pp 315–319

Combined therapy with desferrioxamine and deferiprone in beta thalassemia major patients with transfusional iron overload

Original Article

Abstract

Iron overload is the main cause of morbidity and mortality especially from heart failure in patients with beta thalassemia major (TM). Successful iron chelation is therefore essential for the optimal management of TM. Although desferrioxamine (DFX) has been the major iron-chelating treatment of transfusional iron overload, compliance is a major hindrance in achieving optimal therapeutic results. The availability of oral iron chelation with deferiprone (L1) since 1987 is useful but showed poor efficacy when used alone as compared to DFX. We therefore decided to compare DFX alone with a prospective combined therapy with DFX and L1 in beta thalassemia major patients with iron overload. We studied 91 patients with beta thalassemia major (mean age±SD, 15.02±5.8; range 2–30 years) attending the day care unit for regular transfusional support. They received packed red cells every 3–4 weeks to maintain pretransfusion hemoglobin concentration above 9 g/dl. They had been receiving DFX at a daily dose of 40 mg kg−1 day−1 by subcutaneous infusion for 8–10 h on 4–5 nights each week for the past several years. However, due to various reasons, they had developed considerable transfusional iron overload. These patients were allocated to prospectively receive additional therapy with oral iron chelator L1 at 75 mg kg−1 day−1 body weight in three divided doses with food after informed consent and continued to receive treatment with DFX as per the above dosage. Of the 91 patients, six developed severe gastrointestinal (GI) upset, two agranulocytosis, two arthropathy, one persistently raised liver enzymes, two died owing to sepsis, and two received allogeneic bone marrow transplantation. Amongst the remaining 76 patients, 21 were found noncompliant (not taking DFX regularly, but taking L1 regularly). Thus, in the 55 evaluable patients {6–48 months on combination therapy; mean [(±SD)22±12 months]}, the mean serum ferritin (±SD) fell dramatically from 3,088 (±1,299) ng/ml (DFX alone) to 2,051 (±935) ng/ml (DFX and L1; p<0.001). It is interesting to note that there was also a significant improvement in the myocardial function as assessed by the ejection fraction (p<0.004) and fractional shortening (p<0.05) in those patients (n=42) who could be studied after being on combination therapy for a minimum of 1 year. The study emphasizes that beta thalassemia major patients with transfusional iron overload can be successfully treated with a combination of DFX and L1. Our results also demonstrate a significant statistical improvement after as little as 6 months of combination therapy. Furthermore, these improvements lead to a progressive fall in the mean serum ferritin. Lastly, the study also demonstrates significant improvement in the echocardiographic parameters of myocardial performance in these patients receiving combination therapy.

Keywords

Transfusional iron overload Beta thalassemia major Desferrioxamine (DFX) Deferiprone (L1

References

  1. 1.
    Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, Firmin DN, Wonke B, Porter J, Walker JM, Pennell (2001) Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 22:2171–2179CrossRefPubMedGoogle Scholar
  2. 2.
    Westwood M, Anderson L, Firmin DN, Gatehouse PD, Charrier CC, Wonke B, Pennell DJ (2003) A single breath-hold multiecho T2* cardiovascular magnetic resonance technique for diagnosis of myocardial iron overload. J Magn Reson Imaging 18:33–39CrossRefPubMedGoogle Scholar
  3. 3.
    Ehlers KH, Giardina PJ, Lesser ML, Engle MA, and Hilgartner MW (1991) Prolonged survival in patients with beta-thalassemia major treated with deferioxamine. J Pediatr 540–545Google Scholar
  4. 4.
    Porter JB (2001) Practical Management of iron chelation. Br J Haematol 115:239–252CrossRefPubMedGoogle Scholar
  5. 5.
    Mourad FH, Hoffbrand AV, Sheikh-Taha M, Kousa S (2003) Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassemia patients. Br J Hematol 121:187–189CrossRefGoogle Scholar
  6. 6.
    Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, Allen CJ, Farrell DE, Harris JW (1994) Efficacy of deferioxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 331(9):567–573CrossRefPubMedGoogle Scholar
  7. 7.
    Davis SC, Porter JB (2000) Long term outcome of continuous 24-hour deferioxamine infusion via indwelling intravenous catheters in high-risk beta thalassemia. Blood 95(4):1229–1236PubMedGoogle Scholar
  8. 8.
    Hoffbrand VA, Wonke B (1998) Long-term deferiprone in 51 transfusion-dependant iron overloaded patients. Blood 91(1):295–300PubMedGoogle Scholar
  9. 9.
    Anderson LJ, Wonke B, Prescot E, Holden S, Walker MJ, Pennell J (2002) Comparison of effects of oral deferiprone and subcutaneous desferrioxamine on myocardial iron concentrations and ventricular function in beta thalassemia. Lancet 360:516–520CrossRefPubMedGoogle Scholar
  10. 10.
    Grady RW, Berdoukas VA, Giardina PJ (1998) Iron chelators: combined therapy could be a better approach. Blood 92 (Suppl 1):16bGoogle Scholar
  11. 11.
    Weatherall DJ, Clegg JB (1981) The thalassemia syndromes, 3rd edn. Blackwell, Oxford, U.K.Google Scholar
  12. 12.
    Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, Romeo MA, Forni GL, Gamberini MR, Ghilardi R, Piga A, Cnaan A (2004) Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica (10):1187–1193 (Oct 89)Google Scholar
  13. 13.
    Pootrakul P, Vongsmasa V, Laongpanich P, Wasi P (1981) Serum ferritin levels in thalassemia and the effect of splenectomy. Acta Haematol 12:90–93Google Scholar
  14. 14.
    Villeneuve JP, Bilodeau M, Lepage R, Cote J, Lefebvre M (1996) Variability in hepatic iron concentration measurement from needle-biopsy specimens. J Hepatol 25(2):172–177CrossRefPubMedGoogle Scholar
  15. 15.
    Anguelucci E, Baronciani D, Lucarelli G, Baldassarri M, Galimberti M, Giardini C, Martinelli F, Polchi P, Polizzi V, Ripalti M (1995) Needle liver biopsy in thalassemia: analysis of diagnostic accuracy and safety in 1184 consecutive biopsies. Br J Haematol 89:757–761Google Scholar
  16. 16.
    Wanless IR, Sweeney G, Dhillon AP, Guido M, Piga A, Galanello R, Gamberini RM, Sahwartz E, Cohen AR (2002) Lack of progressive hepatic fibrosis during long-term therapy with Deferiprone in subjects with transfusion-dependent beta-thalassaemia. Blood 100:1566–1569CrossRefPubMedGoogle Scholar
  17. 17.
    Brittenham GM, Allen CJ, Farrell DE, Harris JW (1989) Hepatic iron stores in thalassemia: non-invasive magnetic measurements. Prog Clin Biol Res 309:101–106PubMedGoogle Scholar
  18. 18.
    Wonke B, Wright S, Hoffbrand AV (1998) Combined therapy with deferiprone and desferrioxamine. Br J Haematol 103:361–364CrossRefPubMedGoogle Scholar
  19. 19.
    Balveer K, Pyar K, Wonke B (2000) Combined oral and parenteral iron chelation in beta thalassemia major. Med J Malays 55:493–497Google Scholar
  20. 20.
    Origa R, Bina P, Agus A, Crobu G, Defraia E, Dessi C., Leoni G, Muroni Pier P, Galanello R (2005) Combined therapy with defeprone and desferrioxamine in thalassemia major. Haematologia 90:1309–1314Google Scholar
  21. 21.
    Aydinok Y, Nisli G, Kavakli K, Coker C, Kantar M, Cetingul N (1999) Sequential use of deferiprone and desferrioxamine in primary school children with thalassaemia major in Turkey. Acta Haematol 102:17–21CrossRefPubMedGoogle Scholar
  22. 22.
    Franchini M (2005) Recent acquisitions in the management of iron overload. Ann Hematol 84:640–645CrossRefPubMedGoogle Scholar
  23. 23.
    Naithani R, Chandra J, Sharma S (2005) Safety of oral iron chelator deferiprone in young thalassemics. Eur J Haematol 74:217–220CrossRefPubMedGoogle Scholar
  24. 24.
    Hoffbrand AV, Cohen A, Hershko C (2003) Role of deferiprone in chelation therapy for transfusional iron overload. Blood 102:17–24CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Day Care Unit, Department of HaematologyCollege of Medicine, Sultan Qaboos UniversityMuscatSultanate of Oman

Personalised recommendations