Introduction: Beta thalassaemia major (TM) is a hereditary anaemia affecting 60 000 births worldwide each year. Survival is dependent upon lifelong blood transfusions with cardiac failure secondary to myocardial iron loading being the commonest cause of death. Conventional treatment with the parenteral iron chelator deferoxamine improves mortality but prognosis remains poor and it has been reported that approximately two-thirds of patients maintained on this treatment have myocardial iron loading. More recently, the oral iron chelator, deferiprone has been demonstrated to remove myocardial iron and it has been proposed that in combination with deferoxamine it may have an additive or synergistic effect. Myocardial iron can now be rapidly and reproducibly quantified using the validated cardiac magnetic resonance (CMR) T2* technique. CMR is therefore well suited to assess the efficacy of new therapies for the removal of myocardial iron in TM.

Purpose: To report the primary outcome measure (heart T2*) from a randomized placebo controlled trial testing the hypothesis that the combined therapy of deferiprone and deferoxamine is superior in the removal of myocardial iron than the standard therapy of deferoxamine alone.

Methods: A mobile CMR scanner (1.5T Siemens Sonata) was transported to Cagliari, Italy on 3 occasions. The myocardial T2* was assessed in 167 patients with TM. 65 patients (male 27, female 38, age 30+/−5.2years) with mild-moderate myocardial iron loading (T2* 8–20ms) were randomized to receive either deferoxamine and placebo, or deferoxamine and deferiprone. The primary outcome measure of myocardial T2* was assessed at baseline, 6 and 12 months. Normal myocardial T2* is greater than 20ms.

Results: In the combined treatment group myocardial T2* improved (reducing myocardial iron) from a baseline of 11.7ms to (at 6 months) 14.6ms (+25%; CV 11.9%; p=0.007) and at 12 months 16.8ms (+40%; CV 14.2%; P<0.001). In the placebo controlled group myocardial T2* improved from a baseline of 12.4ms to (at 6 months) 14.2ms (+14%; CV 14%; p=0.15) and at 12 months 15.2ms (+21%; CV 16%; p=0.02). Analysis of covariance showed a significant difference between groups (p=0.017) with the combined group showing greater effects in improving myocardial T2* (figure 1).

Conclusion: In mild-moderate cardiac iron loading the combined therapy of deferiprone and deferoxamine is superior to deferoxamine alone in the removal of myocardial iron in TM.

Figure 1
Figure 1.
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Topics:
cardiac mri, cooley's anemia, deferiprone, deferoxamine, iron, myocardium, psychotherapy, multiple, iron chelating agents, anemia, blood transfusion

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2005, The American Society of Hematology
2005
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