Clinical Scorecard: Gene Therapy for Transfusion-Dependent Thalassemia: EHA–EBMT Consensus on Current Approaches and Future Directions

At a Glance

Key Highlights

• The EHA–EBMT consensus updates prior guidance and provides an algorithm to prioritize TDT patients for GT.

• The selection approach places liver disease assessment at its center, considering cumulative iron exposure, chelation history, hepatitis, alcohol use, and metabolic disorders.

• The consensus also considers cardiomyopathy, endocrinopathy, nephropathy, thrombophilic status, age, iron overload, and organ damage.

• The authors describe GT follow-up requirements as short-, medium-, and long-term in accordance with EMA and FDA requirements.

• The article notes limited follow-up evidence, the need for further survival data, and concerns about treatment cost, center capacity, and equitable access.

Guideline-Based Recommendations

Diagnosis

• Assess liver disease as a central component of GT candidate evaluation, including cumulative history of iron accumulation and chelation, hepatitis infections, alcohol consumption, and metabolic disorders.

• Identify patients requiring invasive liver evaluation; when liver biopsy is performed, the specimen should meet standards for accuracy and representativeness.

• Consider cardiomyopathy, endocrinopathy, nephropathy, and thrombophilic status when assessing candidate eligibility.

Management

• Use the EHA–EBMT selection algorithm to prioritize TDT patients considered most likely to benefit from GT.

• Distinguish patients who are not eligible from those who may become future candidates, taking account of organ damage, iron overload, and age.

• The article describes chronic transfusion with iron chelation as the established basis of TDT management; it also notes luspatercept and mitapivat as additional treatment options.

Monitoring & Follow-up

• Provide short-, medium-, and long-term follow-up after GT in accordance with EMA and FDA requirements.

• Consider liver stiffness measurement (LSM) during TDT follow-up, as discussed in the consensus paper.

• Further follow-up data are needed on the number of treated patients, duration of observation, and survival relative to healthy populations and allogeneic HCT.

Risks

• GT currently entails fully myeloablative conditioning, and the article notes that treatment may be toxic.

• Assess cumulative organ injury associated with prolonged iron-related oxidative stress, including liver disease and other organ complications.

• The article identifies limited experienced-center capacity, high treatment costs, and access disparities—particularly in low- and middle-income countries—as concerns.

Patient & Prescribing Data

GT is one of the two curative treatments for TDT, alongside allogeneic HCT, and has received EMA and FDA approval. The article emphasizes candidate selection, fully myeloablative conditioning, specialist-center requirements, and ongoing follow-up; it provides no dosing details.

Clinical Best Practices

• Base GT selection on a comprehensive assessment of cumulative liver disease and other relevant organ complications.

• Use liver biopsy when indicated and ensure the specimen is accurate and representative.

• Plan follow-up across short-, medium-, and long-term periods in line with EMA and FDA requirements.

• Recognize that the evidence base remains limited and that additional follow-up is needed to clarify long-term outcomes.

Related Resources & Content

1. EHA Specialized Working Group and EBMT Hemoglobinopathies Working Party, PubMed, 2026 -- Update of the decision-making algorithm on selecting transfusion-dependent β-thalassemic patients for gene therapy approaches: joint consensus report

2. The Medicine Maker, 2025 -- This Week’s CGT News: Vertex’s Gene Therapies Show Promise in Younger Children

3. American Journal of Hematology, year not stated -- Correction of Ineffective Erythropoiesis and Normalization of Iron Homeostasis After Exagamglogene Autotemcel in Transfusion-Dependent β-Thalassemia

4. Bone Marrow Transplantation — Understanding Gene Addition and Editing Strategies for Sickle Cell Disease: Insights from the EHA-EBMT Consensus Document

5. the medicine maker — Gene Therapies for Newborns

6. Update of the decision-making algorithm on selecting transfusion-dependent β-thalassemic patients for gene therapy approaches: joint consensus report

7. This Week’s CGT News: Vertex’s Gene Therapies Show Promise in Younger Children

8. Correction of Ineffective Erythropoiesis and Normalization of Iron Homeostasis After Exagamglogene Autotemcel in Transfusion-Dependent β-Thalassemia

9. Update of the decision-making algorithm on selecting transfusion-dependent β-thalassemic patients for gene therapy approaches: joint consensus report on behalf of EHA-specialized working group and EBMT hemoglobinopathies working party.

10. Long-term efficacy and safety results of betibeglogene autotemcel gene therapy for transfusion-dependent β-thalassemia - PubMed

11. Durable Clinical Benefits with Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia | Blood | American Society of Hematology