Liver stiffness is the key determinant of whether β-thalassaemia patients should undergo gene therapy, according to new guidance presented at the European Haematology Association (EHA) congress.
The updated decision-making algorithm recommends that patients with a liver stiffness measurement (LSM) above 8 kPa should not be eligible for gene therapy due to their higher risk of advanced liver fibrosis.
Although liver iron concentration (LIC) is used to determine eligibility at a later stage, assessing LSM is crucial to determining a full history of a patient’s liver health, said Professor Lucia De Franceschi, Professor of Internal Medicine at the University of Verona, Italy, when presenting the update at EHA 2026 in Stockholm.
“Liver iron concentration is just a snapshot, but when you look to liver stiffness, that is a story,” she stressed.
The new guidance, which is produced by EHA and the European Society for Blood and Marrow Transplantation, and has been accepted for publication, is an update on the first gene therapy patient selection algorithm published in 2021.
Prof De Franceschi highlighted the limited experience of gene therapy for β-thalassaemia, with most trials small in size and a paucity of real-world data, as the main difficulty the guideline authors faced.
The panel therefore used the experience of allogeneic haematopoietic stem cell transplantation as a reference for gene therapy selection, since both procedures require a full myeloablative conditioning regimen.
The algorithm does not discriminate between different β-thalassaemia genotypes, but instead places a strong emphasis on iron overload and damage to organs, with the liver identified as a key factor.
It recommends that patients with a LSM of 8 kPa or above should be more thoroughly investigated with a biopsy.
Patients with a LSM <8 kPa should then have LIC assessed and those with LIC ≤7 mg/g can proceed to assessment by a transplant centre.
Patients with LIC 7–14 mg/g should undergo 6–12 months of iron chelation to achieve LIC low enough to proceed to transplant, while those with LIC above 15 mg/g should be investigated further, possibly with biopsy, and should undergo iron chelation.
The algorithm also includes a framework for categorising patients as high-priority, ineligible or assessable, with the latter needing to undergo treatment to become eligible.
It also details guidance on what factors should be collected and monitored during the short-, medium- and long-term follow-up of β-thalassaemia patients who have undergone gene therapy.
This will be crucial for understanding the natural history of the disease, but also for helping the community to understand which factors may affect outcomes from gene therapy, stressed Prof De Franceschi.