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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Bibliographic Details
Published in:Journal of cardiovascular magnetic resonance Vol. 10; no. 1; p. 12
Main Authors: 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
Language:English
Published: London BioMed Central 25.02.2008
BioMed Central Ltd
Elsevier
Subjects:
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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Summary: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
Bibliography: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