To the Editor: Patients with clinically significant forms of β-thalassemia have been historically classified as having a β-thalassemia major or β-thalassemia intermedia phenotype, with the first primarily referring to patients who present with severe anemia during early childhood and require lifelong transfusion therapy and the latter relating to patients who present later in childhood or adolescence with mild–moderate anemia that does not necessitate immediate commitment to regular transfusion therapy.1 In more recent years, the terms transfusion-dependent β-thalassemia (TDT) and non-transfusion-dependent β-thalassemia (NTDT) gradually replaced the two conventional phenotypes, respectively, to highlight the importance of transfusion-dependence in determining the dominant pathophysiology and treatment needs.2 International management guidelines and clinical trial eligibility criteria are now clearly differentiated for TDT and NTDT.3,4 Based on clinical observation, NTDT patients may still require occasional transfusion therapy in cases of infection, pregnancy, or surgery, while some go on to receive more frequent transfusions or become transfusiondependent for various clinical reasons or as heir disease progresses. The rate and determinants of such ‘phenoconversion’ from NTDT to TDT remain poorly understood and have never been previously evaluated. Such data remain essential to fully understand the natural course of β-thalassemia as a disease spectrum
