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).


CONCLUSIONS
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.


BACKGROUND
This trial is registered as NCT00103753.
Tanner
Mark A
MA
Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, London, UK. mark.tanner@imperial.nhs.uk
Galanello
Renzo
R
Dessi
Carlo
C
Smith
Gillian C
GC
Westwood
Mark A
MA
Agus
Annalisa
A
Pibiri
Martina
M
Nair
Sunil V
SV
Walker
J Malcolm
JM
Pennell
Dudley J
DJ
D000284:Administration, Oral; D000328:Adult; D009202:Cardiomyopathies / Q000150:complications / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000077543:Deferiprone; D003676:Deferoxamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007279:Injections, Subcutaneous; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007558:Italy; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011446:Prospective Studies; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D012806:Siderosis / Q000150:complications / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D017086:beta-Thalassemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D007502:Iron Chelating Agents; D011728:Pyridones; D020097:Natriuretic Peptide, Brain; D000077543:Deferiprone; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine