Determinants of Multi-Organ Morbidity in Neo-Transfusion-Dependent Thalassemia: A Cross-Sectional Analysis

<b>Background:</b> This multicenter cross-sectional study aimed to assess the prevalence of vascular, hepatic, cardiac, endocrine, and bone complications and to identify factors associated with their occurrence in adult patients with neo-transfusion-dependent thalassemia (neo-TDT). <b>Methods:</b> A total of 140 adult neo-TDT patients (defined as receiving >4 transfusions/year; mean age 44.3 ± 12.1 years; 56.4% female) were retrospectively enrolled from the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) network. Iron overload (IO) was assessed by magnetic resonance imaging and complications were classified according to established clinical criteria. Logistic regression analyses were performed to investigate associations of complications with age, sex, splenectomy status, chelation therapy, hemoglobin < 9 g/dL, ferritin ≥ 1000 ng/mL, and hepatic, pancreatic, and cardiac IO. <b>Results:</b> Complications affecting fewer than 5% of patients-including leg ulcers, cirrhosis, thrombosis, heart failure, and hypoparathyroidism-were excluded from statistical analysis. Bone metabolism disorders were the most prevalent complications (68.6%), followed by impaired glucose metabolism (15.7%). The prevalence of other complications was: extramedullary hematopoiesis (EMH) 19.3%, pulmonary hypertension (PH) 7.1%, arrhythmias 12.1%, hypogonadism 11.4%, and hypothyroidism 15.0%. Male sex was independently associated with EMH (odds-ratio [OR] = 2.67; <i>p</i> = 0.027). Hepatic IO was the only significant predictor of PH (OR = 4.12; <i>p</i> = 0.047). Arrhythmias were strongly associated with older age (OR = 22.67; <i>p</i> < 0.0001), while both older age (OR = 4.42; <i>p</i> = 0.004) and pancreatic IO (OR = 7.40; <i>p</i> = 0.012) were independently associated with impaired glucose metabolism. No significant associations were identified for hypogonadism, hypothyroidism, or bone metabolism disorders. <b>Conclusion:</b> This study offers updated insights into the burden of complications in neo-TDT patients and highlights specific risk factors that may inform comprehensive, multidisciplinary surveillance strategies.