Gene Therapy for Sickle Cell Disease: Practice Recommendations from the American Society for Transplantation and Cellular Therapy and the International Society for Cell & Gene Therapy.

Table 2. A summary of the key recommendations

• rec-1

  Gene therapy for SCD requires multidisciplinary evaluation, integrating care by hematology, transplant, transfusion medicine, reproductive health, mental health, and social service providers to ensure patients can safely complete the full treatment pathway.

  Management
• rec-2

  Patient selection should extend beyond genotype and disease severity, incorporating organ function, comorbidities, reproductive goals, psychosocial context, and capacity for long-term follow-up.

  Assessment
• rec-3

  Plerixafor-only mobilization is recommended, with granulocyte colony-stimulating factor contraindicated due to safety concerns in SCD.

  Treatment
• rec-4

  Automated red cell exchange before mobilization and conditioning is essential to reduce hemoglobin S levels and minimize peri-procedural complications.

  Prevention
• rec-5

  Myeloablative busulfan conditioning remains standard, requiring pharmacokinetic-guided dosing and proactive management of toxicity, fertility risk, and infection.

  Treatment
• rec-6

  Fertility preservation counseling and intervention should occur early, as current gene therapy approaches are gonadotoxic and do not alter genetic transmission risk.

  Counseling
• rec-7

  Long-term, lifelong surveillance is mandatory, addressing late effects of conditioning, risks related to gene modification, and the evolution of SCD-related organ damage.

  Monitoring
• rec-8

  Participation in national and international registries is strongly encouraged to define durability, late toxicities, and real-world effectiveness of gene therapies.

  Monitoring

Therapeutic Area

Guideline Scope

Inclusion Criteria

• HbSS or HbS β0-thalassemia genotypes
• Age 12 to 45 years
• At least two hospital encounters for VOEs requiring opioids in each of the 2 years preceding gene therapy OR four VOEs in the 24 months before enrollment

Exclusion Criteria

• Two or more α-globin deletions (for β-globin gene addition therapy)
• History of stroke or abnormal transcranial Doppler imaging
• Cancer
• Active viral or fungal infections
• Significant iron overload associated with liver fibrosis

Care Settings

Special Populations