Background/Objectives: Transfusion-dependent β-thalassaemia (TDT) is a lifelong condition requiring coordinated multidisciplinary care. In France, where the disease is rare, transition from pediatric to adult care remains poorly structured, potentially compromising adherence and long-term outcomes. Methods: This national retrospective study evaluated current transition practices and their clinical impact among young adults with TDT. Patients aged 20-25 years in December 2022 were identified from the national NaThalY registry. Those diagnosed and managed in France before age 15 were included. Clinical data were collected for the two years preceding and following transition. Transition practices were assessed using a standardized questionnaire sent to pediatric centers. Results: Thirty-four patients were included (mean transition age: 19 years). The rate of response to the questionnaire was 90.5%, with feedback from 19 centers. Only one-third of centers offered joint pediatric-adult consultations, and one-quarter provided transition-focused education. No written transition protocols were reported. Mean pre-transfusion hemoglobin levels were significantly lower after the transition (8.5 vs. 8.0 g/dL; p = 0.01). Ferritin levels showed a non-significant increase, with no statistically significant changes observed in hepatic or cardiac iron concentrations. Conclusions: This study demonstrates marked heterogeneity and limited formalization of transition practices in France. Development of structured, standardized transition pathways is urgently needed to ensure continuity of care and optimal disease management in adults with TDT.

Topic: 27. Thalassemias Background: Endocrinopathies remain the main complication of iron overload in Transfusion Dependent Thalassemia (TDT), hypogonadism, generally due to oxidative stress related pituitary damage, being the most frequent and often the earliest manifestation. A well-managed chelation therapy initiated during infancy reduces the risk of pubertal delay and hypogonadism. Few data about the current pubertal development of TDT patients receiving DFX are available in literature. Aims: The aim of this national study was to evaluate pubertal development and hypogonadism in TDT adolescents and young adults included in the French National Thalassemia Registry (NaThalY) who received oral chelation with DFX. Methods: This retrospective study concerned all TDT patients included in the national registry (HSCT recipients excluded) who received DFX for at least three years before puberty. Patients were born between 1997 (maximum age of 10 years when DFX was marketed in 2007) and 2009 (evaluable for puberty in 2022). Delayed puberty was defined as lack of testicular development at 14 years old in boys and absence of thelarche at 13 years old in girls. Simple delayed puberty was defined as puberty with a delayed onset but then proceeding normally without the need for any treatment to achieve full pubertal development and hypogonadism as insufficient synthesis of sexual hormones. Results: Fifty patients fulfilled inclusion criteria. Their median age at evaluation was 18 years (range 13-24) and 25 patients (50%) were male. The median duration of DFX chelation before puberty was 7 years (3 -12). 80% of patients were born in France. Regular transfusion regimen and chelation therapy were initiated early, at 1.3 years (0.2-4) and 3 years (1-6) respectively. The median age at puberty onset was 14 years in males and 12 years in females with a median age at first menstruation of 13.5 years (Table). Ten patients (20%) had pubertal development anomalies or hypogonadism. Six patients had simple pubertal delay (n=5) or a transient arrest of puberty with a spontaneous favorable outcome (n=1). One patient developed persistent primary amenorrhea despite a one-year estrogen-progestogen hormone therapy and three others had early secondary amenorrhea: one had a severe chronic iron overload, the second received hormone replacement therapy for a central and peripheral hypogonadism with premature ovarian insufficiency and the third patient had secondary amenorrhea just after a normal pregnancy (the only pregnancy registered in the cohort) currently under investigation. These 10 patients (median age of 20.5 years, range 16-24) had all a beta0/0 genotype and 7/10 experienced a history of severe iron overload (Serum ferritin > 2500 ug/L or liver iron concentration > 15 mg/g). Nonetheless the duration of DFX before puberty and the age at the start of chelation were similar to the other 40 patients with no delay in puberty onset. The final height reached in 35 patients was slightly reduced (-0.7 DS) with a median pubertal growth spurt (difference between final height and prepubertal height) of 18 cm in girls and 21.5 cm in boys. Summary/Conclusion: In adolescents and young adults starting chelation therapy early and receiving before puberty a median of 7 years of DFX, the residual frequency of pubertal anomalies or hypogonadism was of 20% half of them presenting a simple pubertal delay. A pubertal growth spurt was observed leading to a final height only mildly reduced. Specialized follow-up of puberty even in the absence of abnormality is mandatory in TDT children. In the next years the frequency of hypogonadism in young adults could be also assessed.Keywords: Iron overload, Blood transfusion, Iron chelation, beta thalassemia

Introduction: The heterozygous condition for beta-thalassemia mutation associated with an extra functional a-globin gene can produce a Thalassemia Intermedia (TI) phenotype. This genotype is the second in frequency in the French Thalassemia Registry NaThalY that prospectively collects laboratory and clinical data. Materials and Methods: The present report analyses transfusion needs, iron overload (ferritin, hepatic and cardiac iron concentrations), and complication rates in 45 patients included in NaThalY and presenting a heterozygous beta(0) or beta(+)-thalassemia mutation associated with a triplication at HBA locus. This cohort was compared to a cohort of patients with TI due to mutations in the beta-globin gene only and included in the French registry. Results: Patients with an extra functional a-globin gene showed a less severe anemia, lower transfusion needs and lower complication rates than those with TI related to the beta-globin gene only. Nevertheless, some of them displayed complications such as cholelithiasis or extramedullary hematopoiesis. In addition, one third of the cohort needed transfusions and another third was under iron chelation. Conclusion: The genotype associating a heterozygous beta(0) or beta(+)-thalassemia mutation with a triplication at HBA locus should be accurately diagnosed as it could lead to symptomatic anemia and to potential iron overload and iron-related complications even in patients with no transfusion need.

β-thalassemia is an haemoglobinopathy characterized by a defective synthesis of the β-globin chain. To assess the current state of health of paediatric patients with β-thalassemia, data from the French national registry regarding children born between 2005 and 2020 with β-thalassemia intermedia (TI) or major (TM) were collected. A total of 237 patients (median age 7.1 years at last visit) were analysed, of whom 156 (65.8%) were born in France and 162 (68.4%) had a TM phenotype. The probability of survival for children with TM born in France was 98.3% at 15 years. Fifty-four (22.8%) children received a haematopoietic stem cell transplant with a success rate of 88.8%. Hepatic and cardiac iron overload monitoring in non-transplanted patients showed moderate overload in 15.7% (18/115) and 7.1% (7/99) of cases, respectively, while clinical complications were found in only 4 patients with TM (hepatic in 3 cases). At last visit, mean ferritinemia was 1293 ng/ml (±759). Overall, less than 10% of children underwent splenectomy. No significant impact of the disease on growth or academic achievement was observed. Deferasirox was the main first-line chelator, prescribed in 78.2% of cases, with side effects reported in 11.7% of instances.