Thalassemia in europe: A cross-border real-world data analysis from the radeep registry

Abstract

Abstract Introduction Advances in understanding the pathophysiology and clinical heterogeneity of Thalassemia (THAL) have enabled the development of new therapeutic strategies and patient stratification. However, limited availability of cross border standardized data and insufficient integration into health policy frameworks continue to hamper tailored clinical care pathways based on equitable resource allocation and to advance research in personalized medicine. We present the results of the first European dataset of THAL patients captured in the RADeep Registry, endorsed by the European Hematology Association (EHA), from 2013-12-16 to 2025-05-26. The aim is to characterize the disease burden, the occurrence of key clinical outcomes: acute events and progressive organ damage, treatment patterns and healthcare resource utilization. Methods Patient individual data (PID) is collected prospectively and longitudinally from health care providers directly or through national registries within the RADeep participating EU countries. The dataset includes patients with beta-thalassemia major and intermedia (BT) and alpha-thalassemia/Hemoglobin H disease (AT) excluding those who undergone hematopoietic stem cell transplantation (HSCT) or gene therapy prior to registry enrollment. Results on clinical outcome and disease severity were analyzed stratified by age (pediatric <18 and adult) and transfusion dependence (TD, NTD). TD was defined as having ≥6 transfusion events over a 12-month period. Results Standardized PID was collected on 900 THAL patients. Fifty one centers reported data on BT (Belgium, 5; Cyprus, 3; Denmark, 1; Greece, 1; Italy, 23 and Spain, 18) while only 14 reported on AT (Belgium, 1; Cyprus, 2; Denmark, 1; Greece, 1; Italy, 3 and Spain, 1) likely due to lower reporting rate because of the milder clinical phenotype of AT. Overall, 81.3% (732) of patients were diagnosed with BT and 18.7% (168) with AT. The cohort was gender-balanced across all countries (54.6% female). The median age was significantly lower in the AT group (28 y.o.) compared to the BT group (39 y.o.), which is consistent with the lower historical prevalence of AT and recent migration waves from Asian countries. TD was remarkably different among pediatric and adult patients in both BT (73.9% vs 90.7%) and AT (2% vs 15.5%) suggesting possible worsening of intermediate phenotypes over time. Cyprus had the highest transfusion dependency rate (93% vs. overall 85.8%) and was the only country with a mean hemoglobin level above the overall average (10.7 g/dL vs. 10.1 g/dL). Hydroxyurea usage was reported in 4.8% of BT and 2.1% of AT patients. Splenectomy was performed in 36.6% of BT and 6.3% of AT patients, showing marked differences between adult and pediatric populations: 50.8% vs. 2.2% for BT, and 8.4% vs. 2.1% for AT, which may reflect outdated clinical practices in adult THAL patients. Regarding specific treatments, in AT 29% of patients received folic acid and 19% vitamin D, with similar rates across TD status and age groups. In BT, vitamin D use was comparable, while folic acid was prescribed more frequently in pediatric than adult patients (26% vs 12%). At least one clinical manifestation of chronic organ damage was reported in 62.1% of BT, being the most frequent osteoporosis (30.9%) and hypogonadism (20.1%). Notably 36.5% of AT patients presented at least one clinical manifestation of chronic organ damage, with osteoporosis (14.9%) and hepatic fibrosis (12.2%) as the most reported. A total of 14% of BT and 14.9% AT patients presented at least one acute complication related to the disease that led them to an emergency room visit or hospitalization in the last 24 months. Similar distributions were observed when stratifying by TD and age groups. Conclusions These initial findings support the idea that AT remains underappreciated and underreported compared to BT, while also highlighting significant rate of clinical complications, especially in the adult population. As a cross-border patient registry, RADeep is capable of pooling and standardizing data across Europe, enabling systematic monitoring of THAL, and robust data-driven research to optimize care pathways. In this context, it provides a framework for generating regulatory-grade real-world evidence and offers standardized data to support patient cohort identification for advanced clinical studies in THAL.