Apparent plateaus during iron chelation in transfusion-dependent β-thalassemia: interpretation and clinical...

Transfusion-dependent β-thalassemia (TDT) has become a chronic, survivable condition, but transfusional iron overload remains a central driver of cardiac, hepatic, and endocrine morbidity. Clinicians increasingly encounter patients whose iron indices 'stall' despite seemingly appropriate chelation, creating uncertainty about whether the problem is correctable (iron balance, adherence, dosing) or reflects a harder biological limitation in iron mobilization.

A narrative review of pivotal randomized trials, prospective cohorts, and major observational MRI datasets evaluating deferoxamine, deferiprone, deferasirox, and combination regimens in TDT was performed. Literature was identified via structured searches of PubMed and key hematology/cardiometabolic journals (2000-February 2026), prioritizing primary studies with MRI liver iron concentration (LIC) and cardiac T2* endpoints, and supplemented by regulatory prescribing information for safety monitoring.

Many 'plateaus' are predictable steady-state iron balance-ongoing transfusional iron input matches achievable chelator-mediated excretion-and can be addressed by quantifying iron intake, verifying adherence, and rationally intensifying therapy. A second category, a hypothesized 'biological ceiling,' may arise when stored iron becomes less accessible (slow-turnover pools, tissue remodeling, altered export). Clinicians can disentangle these mechanisms by integrating transfusion iron input calculations with serial multi-organ MRI trajectories, then tailoring chelator strategy to the dominant iron compartment and organ risk.