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

Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, Pibiri M, Nair SV, Walker JM, Pennell DJ - J Cardiovasc Magn Reson (2008)

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, London, UK. mark.tanner@imperial.nhs.uk

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.

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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.
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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.

Mentions: There was a significant reduction in ferritin, from 2057 μg/L (CV 7.6%) at baseline to 666 μg/L (CV 13.2%) at 12 months (ANOVA p < 0.001; figure 5).


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

Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, Pibiri M, Nair SV, Walker JM, Pennell DJ - J Cardiovasc Magn Reson (2008)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2289829&req=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.
Mentions: There was a significant reduction in ferritin, from 2057 μg/L (CV 7.6%) at baseline to 666 μg/L (CV 13.2%) at 12 months (ANOVA p < 0.001; figure 5).

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, London, UK. mark.tanner@imperial.nhs.uk

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.

Show MeSH
Related in: MedlinePlus