Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2008 Feb 25;10(1):12.
doi: 10.1186/1532-429X-10-12.

Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction

Mark A Tanner  1 , Renzo Galanello, Carlo Dessi, Gillian C Smith, Mark A Westwood, Annalisa Agus, Martina Pibiri, Sunil V Nair, J Malcolm Walker, Dudley J Pennell
Affiliations
Clinical Trial

Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction

Mark A Tanner et al. J Cardiovasc Magn Reson. .

Abstract

Background: In thalassemia major (TM), severe cardiac siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial siderosis, but has not been prospectively examined in severe myocardial siderosis.

Methods: T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up.

Results: At baseline, deferoxamine was prescribed at 38 +/- 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 +/- 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 +/- 0.98 ms to 7.9 +/- 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 +/- 10.9% to 65.6 +/- 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) microg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 +/- 2.9 ms to 10.8 +/- 7.3 ms; p = 0.006).

Conclusion: In patients with severe myocardial siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans.

Trial registration: This trial is registered as NCT00103753.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Myocardial T2* improved significantly between baseline and 12 months. Standard error bars are shown. The p values shown are post-hoc analyses for 0–6 months, and 0–12 months.
Figure 2
Figure 2
Liver T2* improved significantly between baseline and 12 months. Standard error bars are shown. The p values shown are post-hoc analyses for 0–6 months, and 0–12 months.
Figure 3
Figure 3
There was a significant improvement in LV ejection fraction over 12 months. Standard error bars are shown. The p values shown are post-hoc analyses for 0–6 months, and 0–12 months.
Figure 4
Figure 4
LV end-systolic volume index decreased significantly over 12 months. Standard error bars are shown. The p values shown are post-hoc analyses for 0–6 months, and 0–12 months.
Figure 5
Figure 5
There was a significant reduction in serum ferritin over 12 months. The vertical axis shows the geometric mean of ferritin. Standard error bars are shown. The p values shown are post-hoc analyses for 0–6 months, and 0–12 months.
See this image and copyright information in PMC

References

    1. Weatherall DJ, Clegg JB. The thalassaemia syndromes. 4. Oxford, England: Blackwell Science; 2001.
    1. Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A, Martin M, Koren G, Cohen AR. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med. 1994;331:574–8. doi: 10.1056/NEJM199409013310903. - DOI - PubMed
    1. 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. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004;89:1187–93. - PubMed
    1. Telfer P, Coen PG, Christou S, Hadjigavriel M, Kolnakou A, Pangalou E, Pavlides N, Psiloines M, Simamonian K, Skordos G, Sitarou M, Angastiniotis M. Survival of medically treated thalassemia patients in Cyprus. Trends and risk factors over the period 1980–2004. Haematologica. 2006;91:1187–92. - PubMed
    1. Modell B, Khan M, Darlison M. Survival in beta thalassaemia major in the UK: Data from the UK Thalassaemia Register. Lancet. 2000;355:2051–2. doi: 10.1016/S0140-6736(00)02357-6. - DOI - PubMed

Publication types

MeSH terms

Associated data