Pediatric

Hemoglobinopathies are a group of genetic disorders affecting the structure or production of the hemoglobin molecule. The most common conditions in this group consist of sickle cell anemia (SCD) and β-Thalassemia, two disorders that come with a significant burden for both patients and the healthcare system as a whole. Geographically, SCD predominantly occurs in sub-Saharan Africa, whereas β-Thalassemia is most commonly found in mediterranean countries, the Middle-East and India. However, due to migration streams, physicians in Northern Europe are increasingly being confronted with these diseases.

In this daily highlights video, Dr Victoria Bordon Cueto De Braem, pediatrician responsible for bone marrow transplantations in the pediatric department of the Ghent University Hospital, shares some of the highlihghts related to SCD and β-Thalassemia presented during EBMT 2025.

First of all, Dr Bordon underscored that the current managament of both SCD and β-Thalassemia is predominantly focussed on symptom control. For SCD, the standard treatment consists of hydroxyurea in combination with transfusions whenever necessary, while β-Thalassemia is usually managed with a hypertransfusion protocol and anticoagulation. During EBMT, however, interesting data were presented on potentially curative treatment strategies for these patients.

In a first abstract, data from an EBMT registry provide important data on the efficacy of allogenic stem cell transplantations in patients with SCD. In total, this analysis included more than 1,800 patients from 36 countries and showed high rates of overall (OS) and event-free survival (EFS) across age groups. After 2 years of follow-up, OS and EFS rates among children were reported at 95% and 93%, respectively, while these rates reached 93% and 90% in adults.¹

In addition, two interesting abstracts were presented in which conditioning therapy with treosulfan, triotepa, fludarabine and ATG (FTTA) was used in the treatment of SCD and β-Thalassemia.^2,3 In a first cohort, including 80 SCD patients who were conditioned with ATGG prior to a sibling haemopoietic cell transplantation (HCT), all patients obtained normal hematopoiesis with resolution of sickle related manifestation. There were no transplant-related deaths and only one case of secondary graft failure was observed.² The second study included 81 patients with β-Thalassemia Major who recieved ATTG prior to a matched related, unrelated, or haploidentical HSCT. Of note, two thirds of patients in this cohort had Pesaro class III disease. FTTA was again associated with excellent outcomes with an OS rate of 86% and an EFS rate of 81% at last follow-up. Veno-occlusive disease (VOD) was observed in 11% of the patients, including only 2 severe cases.³

In the last part of her overview, Dr Bordon turns the attention to gene therapy with exagamglogene autotemcel (exa-cel) for patients with SCD or β-Thalassemia.^4,5 A first of these presentation discussed the results obtained with exa-cel in 46 SCD patients treated in the phase III CLIMB SCD-121 and  -131 studies.⁴ Elimination of vaso-occlusive crises (VOCs) was achieved in 90% of these patients, with clinically meaningful and sustained increases in fetal and total hemoglobin (Hb). The second study included 56 transfusion-dependent β-Thalassemia patients with a median age of 21 years. Durable transfusion independence was achieved in 94% of these patients following exa-cel, with associated clinically meaningful and sustained increases in fetal total Hb for up to 5 years of follow-up.⁵

Based on these results, Dr Bordon believes that we are at a turning point in the management of SCD and β-Thalassemia and urges for the increased use of these potentially curative treatment options instead of traditional symptom control in patients suffering from these conditions.