Efficacy and safety of calcium channel blockers in preventing cardiac siderosis in thalassemia patients: An updated meta-analysis with trial sequential analysis.

OBJECTIVES: Iron overload in patients with thalassemia represents a serious complication by affecting numerous organ systems. This meta-analysis aims to establish an evidence regarding the effect of amlodipine on cardiac iron overload in thalassemia patients. METHODS: We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for all relevant randomized controlled trials (RCTs). The primary outcomes were cardiac T2* and myocardial iron concentration (MIC). Secondary outcomes were liver iron concentration (LIC), risk of Gastrointestinal (G.I.) upset and risk of lower limb edema. We used Hedges' g to pool continuous outcomes, while odds ratio was used for dichotomous outcomes. RESULTS: Seven RCTs were eligible for this systematic review and meta-analysis, comprising of 233 patients included in the analysis. Amlodipine had a statistically significant lower MIC (Hedges' g = -0.82, 95% confidence interval [CI] [-1.40, -0.24], p < .001) and higher cardiac T2* (Hedges' g = 0.36, 95% CI [0.10, 0.62], p = .03). Amlodipine was comparable to standard chelation therapy in terms of the risk of lower limb edema and GI upset. CONCLUSION: Our meta-analysis found that amlodipine significantly increases cardiac T2* and decreases MIC, hence decreasing the incidence of cardiomyopathy-related iron overload in thalassemia patients.

Treatment of superficial siderosis with iron chelation therapy.

Superficial siderosis is caused by recurrent haemorrhage in the subarachnoid space leading to haemosiderin deposition. It typically causes the triad of ataxia, deafness and myelopathy. We report a patient who developed superficial siderosis following neurosurgery for syringomyelia and who had an improvement in his hearing and mobility following treatment with a new iron chelation therapy that can penetrate the blood-brain barrier. It provides an intriguing insight into a therapy that could potentially modify the course of this rare neurodegenerative disorder. Further studies are required to assess the clinical efficacy of deferiprone in superficial siderosis.

Follow-up report on the 2-year cardiac data from a deferasirox monotherapy trial.

The trial CICL670AUS04 was a single-arm, open-label study of the cardiac efficacy of 18 months of deferasirox monotherapy [1]. Cardiac response in this study was related to the degree of liver siderosis. Patients with mild to moderate liver siderosis improved their cardiac T2* while more severely siderotic patients did not, regardless of initial cardiac iron burden. In this letter, we report 2-year data in those patients who completed a 6-month extension phase (N 5 10). Cardiac and liver iron improved steadily during the 24-month period, with final cardiac T2* and LIC improving 37% and 27%, respectively, in this cohort. Serum ferritin and LVEF were not statistically different at anytime-point. When the extension phase (18-24 months) was considered in isolation, serum ferritin, liver iron concentration, and left ventricular ejection fraction were nearly identical to 18 month results. Despite this, cardiac T2* continued to trend higher, increasing 12.7% from 9.5 ms to 10.7 ms (P 5 0.06). Thus defersirox continued to demonstrate cardiac efficacy in patients with mild to moderate hepatic siderosis throughout 2 years of therapy.

Update on thalassemia treatment in Taiwan, including bone marrow transplantation, chelation therapy, and cardiomyopathy treatment effects.

Over the past few decades, Taiwan has seen striking improvements in the life expectancy of its 400 registered beta-thalassemia major (beta-TM) patients due mainly to adequate transfusion regimens and effective iron chelation therapy. Since 1995, Taiwanese citizens have enjoyed universal health care through National Health Insurance (NIH), receiving comprehensive treatment at minimal cost. In 1984, a national program for thalassemia prevention, control, and hematopoietic stem cell transplantation (HSCT) was initiated. Recent data show 1- and 2-year event-free survival rates of 85 and 78%, respectively. Chelation agents like deferoxamine (DFO), deferiprone (L1) and deferasirox (DFRA) are available in Taiwan, and therapy is tailored to individuals based on drug availability and tissue distribution of iron load. Intensive chelation regimens combining L1 and DFO are recommended in patients with cardiac complications, while DFRA has been found to be effective in reducing serum ferritin, with acceptable side effects. Here, we report advances in thalassemia treatment in Taiwan and suggest treatment guidelines.

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

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.

High dosage desferrioxamine therapy in a female patient with acquired aplastic anaemia and transfusion siderosis.

A 32 year old woman with severe aplastic anaemia required frequent transfusions and consequently developed hyperferrioxaemia (54 microMol/l) and hyperferritinaemia (1,700 ng/ml). For the treatment of transfusion siderosis she was given 18 high dose courses each comprising 35 g of desferrioxamine. Because of pre-existing thrombocytopenia (platelet count 5 X 10(9)/l) the iron chelating agent was given by continuous intravenous infusion over 3 1/2 days. High dose desferrioxamine had to be abandoned because of severe bone pain. The desferrioxamine infusions achieved a negative iron balance, iron loss after each infusion being 100 to 200 mg in the urine and 400 mg in the faeces. Serum iron and ferritin concentrations fell almost to normal. This report shows that faecal iron excretion must be taken into account in assessing the balance of iron input and output during desferrioxamine treatment.