Current approach to iron chelation in children

Abstract

SummaryTransfusion-dependent children, mostly with thalassaemia major, but also and occasionally to a more significant degree, with inherited bone marrow failures, can develop severe iron overload in early life. Moreover, chronic conditions associated with ineffective erythropoiesis, such as non-transfusiondependent thalassaemia (NTDT), may lead to iron overload through increased gut absorption of iron starting in childhood. Currently, the goal of iron chelation has shifted from treating iron overload to preventing iron accumulation and iron-induced end-organ complications, in order to achieve a normal pattern of complication-free survival and of quality of life. New chelation options increase the likelihood of achieving these goals. Timely initiation, close monitoring and continuous adjustment are the cornerstones of optimal chelation therapy in children, who have a higher transfusional requirements compared to adults in order to reach haemoglobin levels adequate for normal growth and development. Despite increased knowledge, there are still uncertainties about the level of body iron at which iron chelation therapy should be started and about the appropriate degree of iron stores' depletion.

Thalassemia 2016: Modern medicine battles an ancient disease

“…However, desferrioxamine is not suitable for all patients and even early on, investigators were working on new chelators [32]. At the present time there are three chelators, two oral and one parenteral, in routine use, all of which are effective to varying degrees and which have differing adverse effects [33,34]. The availability of orally active chelators has greatly improved compliance which is still an issue for patients requiring this treatment on a lifelong basis.…”

“…The availability of orally active chelators has greatly improved compliance which is still an issue for patients requiring this treatment on a lifelong basis. New combination therapy approaches and intensification of dosing are promising in terms of increased efficacy [33]. While long hypothesized but not absolutely proven [35], recent in vitro evidence demonstrates synergistic chelation efficacy using a combination of different types of chelators [36].…”

“…An algorithm has been developed for routine use of cardiac MRI to guide long term optimum chelation [40]. Ferritin remains useful in young children, for whom the use of MRI requiring sedation is problematic and needs to be weighed individually [33].…”

Information Technology–Assisted Treatment Planning and Performance Assessment for Severe Thalassemia Care in Low- and Middle-Income Countries: Observational Study (Preprint)

“…Categorized clinical notes allows doctors to find context-appropriate details. Continuous dose adjustment is critical to the success of iron chelation therapy [39,40]: The system prompts if the medication doses do not agree with treatment protocols based upon laboratory results and patient's weight. The system also tracks compliance to treatment by tracking the purchase/issue of drugs [41] which are dispensed directly by centers.…”

Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia

“…These were initially introduced as second line agents in children six years and older with β -thalassaemia major, or in people when DFO is contraindicated or found to be inadequate (Fisher 2013). These oral agents are becoming more commonly used, particularly DFX, because of the ease of administration compared to subcutaneous or intravenous DFO (Aydinok 2014). The price of therapy varies depending on the formulation and the dose prescribed, but treatments can cost in excess of £1000 per month.…”