Objective:

The article describes the EHA–EBMT consensus update on selecting patients with transfusion-dependent thalassemia (TDT) for gene therapy (GT), incorporating newer treatments, transplantation data, and gene therapy evidence.

Approach:

• Evidence reviewed: The panel reviewed newer TDT treatments, allogeneic hematopoietic cell transplantation (HCT) data, clinical studies of gene addition and gene editing, available follow-up, and literature on early mortality and organ complications.
• Candidate assessment: The revised selection flow chart places liver disease assessment centrally and considers cumulative iron-related injury and the history of liver disease, including iron accumulation and chelation, hepatitis, alcohol use, and metabolic disorders. The panel also considered other organ complications and thrombophilic status.
• Follow-up: The authors established short-, medium-, and long-term follow-up in accordance with EMA and FDA requirements.

Key Findings:

• The consensus updates a 2021 document focused on gene addition and incorporates advances in treatments, transplantation, and gene therapy studies.
• The panel treats hepatic fibrosis as a marker of oxidative stress accumulated over time. Liver assessment considers tissue injury and the history of liver disease, not iron burden alone.
• The panel identified patients who require liver biopsy to establish liver disease before GT and stated that biopsy samples should be accurate and representative.
• Selection considerations include cardiomyopathy, endocrinopathy, nephropathy, thrombophilic status, age, iron overload, and organ damage.
• Follow-up data for TDT patients treated with GT remain limited in patient numbers and duration. Further information is needed, including on survival relative to healthy populations and HCT.

Interpretation:

The authors describe the EHA–EBMT algorithm as a means of prioritizing TDT patients considered most likely to benefit from GT, while noting that further follow-up evidence is needed.

Limitations:

• Follow-up data after GT in TDT remain limited in both the number of treated patients and duration of observation.
• The authors raise concerns about access because of GT costs, the scarcity of experienced centers, and health-system constraints, particularly in low- and middle-income countries.

Conclusion:

The EHA–EBMT algorithm is intended to support prioritization of TDT patients for gene therapy.