We sincerely thank Piperno and colleagues for their comment1 on our work.2 We fully agree on the importance of not overlooking hyperferritinemia in patients with β-thalassemia trait, a condition often underestimated. In the suspicion of iron overload, liver magnetic resonance imaging should be offered for accurate assessment of parenchymal iron burden, and standardized diagnostic cut-offs are needed to better stratify risk and guide treatment decisions. Our study showed that mini-phlebotomies are an effective and well-tolerated approach, although sometimes prolonged treatment may be required. Subcutaneous bolus injections of desferrioxamine, while theoretically feasible, remain scarcely explored in the literature and seldom used in clinical practice.3 We, therefore, agree that, in selected cases, such as patients with moderate anemia or severe iron overload, access to other effective therapies should be considered. Oral iron chelators, already validated in transfusion- and non-transfusion-dependent thalassemias,4 may represent a more practical option, but their use should be restricted to carefully selected patients, as they are not devoid of risks, particularly concerning renal, gastrointestinal, visual, and hearing toxicity.
Given the high prevalence of β-thalassemia trait and the fact that a subset of individuals may develop clinically relevant multifactorial iron overload, further studies are warranted to explore novel therapeutic approaches, including oral iron chelators, in this underserved population.
Footnotes
- Received August 28, 2025
- Accepted September 2, 2025
Correspondence
Disclosures
DG is a consultant for Sanofi, Kedrion-Pharmacosmos, Vifor Pharma and Novo Nordisk. FB has no conflicts of interest to disclose.
Contributions
References
- Piperno A, Mariani R. β-thalassemia trait and iron overload: is it time to consider oral iron chelators? Comments on: “A case series of patients with β-thalassemia trait and iron overload: from multifactorial hepcidin suppression to treatment with mini-phlebotomies”. Haematologica. 2026; 111(2):768-769. Google Scholar
- Busti F, Castagna A, Marchi G. A case series of patients with β-thalassemia trait and iron overload: from multifactorial hepcidin suppression to treatment with mini-phlebotomies. Haematologica. 2025; 110(5):1226-1231. Google Scholar
- Franchini M, Gandini G, de Gironcoli M, Vassanelli A, BorgnaPignatti C, Aprili G. Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload. Blood. 2000; 95(9):2776-2779. Google Scholar
- Cappellini MD, Scaramellini N, Leoni S, Motta I. Iron chelation therapy. Adv Exp Med Biol. 2025; 1480:361-370. Google Scholar
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