Iron overload is the most important cause of mortality in patients with thalassaemia major. Iron chelation is therefore a critical issue in the management of these patients and others with transfusion-dependent haemoglobinopathies and congenital anaemias. In recent years, significant developments have been made in the assessment of iron overload, including the use of magnetic resonance imaging for measuring liver and cardiac iron. Advances in the modalities available for iron chelation, with the advent of oral iron chelators including deferiprone and deferasirox in addition to parenteral desferrioxamine, have expanded treatment options. A group of Australian haematologists has convened to formulate guidelines for managing iron overload on the basis of available evidence, and to describe best consensus practice as undertaken in major Australian Haemoglobinopathy units. The results of their discussions are described in this article, with the aim of providing guidance in the management of iron overload in these patients.

Acquired hemophilia A (AH) is a rare and serious acquired bleeding disorder where prompt and correct diagnosis is crucial, and immune suppression is often required for factor VIII (FVIII) autoantibody eradication. The acquired FVIII deficiency usually manifests as bruises and bleeding, and treatment such as FVIII has limited efficacy because of the neutralizing FVIII inhibitor. Expensive bypassing agents such as recombinant activated factor VII (rFVIIa) may be required to treat clinically significant bleeding. This report summarizes the experience related to AH from a large Australian hemophilia center based in South Australia. We identified 25 patients retrospectively over 12 years (1997 to 2008) and reviewed diagnostic features, treatment for bleeds and to eradicate the autoantibody, treatment response, and survival outcomes. The incidence in South Australia was 1.20 cases per million/year with a median age of 78 years with an approximately equivalent sex ratio (12 males versus 13 females); median FVIII and inhibitor titer were 2.5 IU/dL and 11.0 BU/mL, respectively. Twenty-four patients were evaluated further. Thirteen patients (54%) required hemostatic agents, and rFVIIa was used in seven for major bleeds, of which four were limb or life threatening. Eighteen patients were treated by hematologists with immune suppression, and combination steroid and azathioprine was used most commonly to eradicate autoantibody; 15 of these 18 achieved remission (i.e., 83% response rate). Two patients had persistent low-titer inhibitor when treatments were withdrawn, and one died of a fatal bleed shortly after starting treatment. One had spontaneous remission. Five patients (33%) relapsed, three in less than 6 months after starting treatment; all were retreated successfully. Rituximab was used in six patients for high-titer inhibitor, second relapse, two life-threatening bleeds, underlying lymphoma, and steroid intolerance, respectively. Overall mortality was 25% ( N = 6), five of whom were not treated. Advanced age and lack of treatment were predictive of poor survival outcomes. The very elderly (>75 years of age) may warrant a different treatment modality such as rituximab, which is potentially more tolerable and efficacious.

There is still a clinical need for a well-tolerated and safe iron chelator for the treatment of transfusional iron overload. We describe the pharmacokinetic properties and safety data after 7 days of dosing of FBS0701, a novel oral, once-daily iron chelator. Design and MethodsThis phase 1b dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload, was conducted in 16 adult patients with iron overloaded consequent to transfusions. FBS0701 was given daily for 7 days at doses up to 32 mg/kg and was well tolerated at all dose levels. ResultsPharmacokinetics showed dose-proportionality. The maxium plasma concentration (Cmax) was reached within 60-90 minutes of dosing and the drug was rapidly distributed at the predicted therapeutic doses. The plasma elimination half-life (t1/2) was approximately 19 hours. There were no serious adverse events associated with the drug. ConclusionsOn the basis of these safety and pharmacokinetic data, FBS0701 warrants further clinical evaluation in patients with transfusional iron overload.

Very low cardiac T2* values <10 ms are common in adults with beta thalassaemia and are significantly associated with risk of cardiac events. This permits the use of individually targeted chelation strategies which are more effective in removing cardiac iron.

Once-daily deferasirox over 1 yr significantly increased myocardial T2* and reduced LIC. This confirms that single-agent deferasirox is effective in the management of cardiac iron, especially for patients with myocardial T2* >10 ms (Clinicaltrials.gov identifier: NCT00673608).