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 pros...

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Veröffentlicht in:	Journal of cardiovascular magnetic resonance Jg. 10; H. 1; S. 12
Hauptverfasser:	Tanner, Mark A, Galanello, Renzo, Dessi, Carlo, Smith, Gillian C, Westwood, Mark A, Agus, Annalisa, Pibiri, Martina, Nair, Sunil V, Walker, J Malcolm, Pennell, Dudley J
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London BioMed Central 25.02.2008 BioMed Central Ltd Elsevier
Schlagworte:	Administration, Oral Adult Angiology beta-Thalassemia - complications beta-Thalassemia - drug therapy beta-Thalassemia - metabolism beta-Thalassemia - pathology beta-Thalassemia - physiopathology Cardiology Cardiomyopathies - complications Cardiomyopathies - drug therapy Cardiomyopathies - etiology Cardiomyopathies - metabolism Cardiomyopathies - pathology Cardiomyopathies - physiopathology Cardiomyopathy Care and treatment Chelation therapy Deferiprone Deferoxamine - administration & dosage Deferoxamine - adverse effects Deferoxamine - therapeutic use Diagnosis Drug Therapy, Combination Female Ferritins - blood Heart diseases Humans Imaging Injections, Subcutaneous Iron - metabolism Iron Chelating Agents - administration & dosage Iron Chelating Agents - adverse effects Iron Chelating Agents - therapeutic use Italy Liver - drug effects Liver - metabolism Magnetic Resonance Imaging Male Medicine Medicine & Public Health Myocardium - metabolism Natriuretic Peptide, Brain - blood Prevention Prospective Studies Pyridones - administration & dosage Pyridones - adverse effects Pyridones - therapeutic use Radiology Severity of Illness Index Siderosis - complications Siderosis - drug therapy Siderosis - etiology Siderosis - metabolism Siderosis - pathology Siderosis - physiopathology Stroke Volume - drug effects Thalassemia Treatment Outcome Ventricular Dysfunction, Left - drug therapy Ventricular Dysfunction, Left - etiology Ventricular Dysfunction, Left - metabolism Ventricular Dysfunction, Left - physiopathology Serum Ferritin Cardiovascular Magnetic Resonance Deferiprone Thalassemia Major Deferoxamine
ISSN:	1097-6647, 1532-429X, 1532-429X
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Zusammenfassung:	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%) μg/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
Bibliographie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1097-6647 1532-429X 1532-429X
DOI:	10.1186/1532-429X-10-12