Monitoring long-term efficacy of iron chelation treatment with biomagnetic liver susceptometry.
In patients with thalassemia, the assessment of liver iron concentration (LIC) can be used to initiate chelation treatment with desferrioxamine (DFO), deferiprone (DFP), or novel chelators (deferasirox); to adjust chelation dose according to the actual blood transfusion rate; and to monitor chelation efficacy. The results from measurements by SQUID biomagnetic liver susceptometry in the LIC range 17-11,500 microg/g of liver in about 1000 patients were used to derive nonstandard parameters, which may be useful in the treatment monitoring of patients with thalassemia. From these measurements, including liver volumes, the documented chelation dose rates, and the blood transfusion rates, the chelator index (equivalent Therapeutical Index), the total body iron elimination rate, and the molar efficacy were calculated. Chelator indices (CIs) ranged from 0.1 to 11.7 mmol/d/g of Fe for DFO, with a threshold of CI greater than 1.2 mmol/d/g of Fe indicating DFO toxicity. For DFP, CI ranged from 0.1 to 23.2 mmol/d/g of Fe. In long-term studies (2 and 4 years), mean molar efficacies of DFO and DFP were found to be quite stable with 17.6 +/- 4.8% and 4.9 +/- 1.4%, respectively. Currently, specific chelation dose is based upon body weight. Because liver iron measurements by biosusceptometry are now regularly available in Europe and America, as well as quantitative MRI worldwide, these methods may be used to adjust chelation treatment regimens to body iron stores.
Fischer
Roland
R
University Medical Center Hamburg-Eppendorf, Department of Molecular Cell Biology, Hamburg, Germany. rfischer@mail.cho.org
Piga
Antonio
A
Harmatz
Paul
P
Nielsen
Peter
P
D000465:Algorithms; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001803:Blood Transfusion; D015913:Chelation Therapy; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019190:Iron Overload / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D013789:Thalassemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D001565:Benzoates; D007502:Iron Chelating Agents; D011728:Pyridones; D014230:Triazoles; D000077543:Deferiprone; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox