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American Society for Transplantation and Cellular Therapy and the International Society for Cell & Gene TherapyHematology2026advanced

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.

Published by American Society for Transplantation and Cellular Therapy and the International Society for Cell & Gene Therapy

8Recommendations
72References
2Tables
1Figures

Summary

AI-generated

Gene therapy has emerged as a transformative treatment option for individuals with sickle cell disease (SCD). However, the complexity of patient selection, stem cell mobilization, manufacturing, conditioning, and long-term follow-up underscores the need for standardized, evidence-informed clinical guidance to support shared decision-making and promote safe care delivery.

sickle cell diseasegene therapyhematologyASTCTISCTplerixaforbusulfanhematopoietic stem cell transplantation

Key Takeaways

  • 1
    Gene therapy requires a multidisciplinary evaluation and capacity for long-term follow-up.
  • 2
    Patient selection involves evaluating not just genetics, but also social context, organ function, and reproductive goals.
  • 3
    Plerixafor-only mobilization is recommended; G-CSF is contraindicated.
  • 4
    Automated red cell exchange prior to mobilization and conditioning is essential to mitigate complications.
  • 5
    Myeloablative busulfan conditioning requires pharmacokinetic-guided dosing and proactive toxicity management.
  • 6
    Early fertility preservation counseling is imperative as current conditionings are gonadotoxic.
  • 7
    Lifelong surveillance is mandatory to monitor for late effects of conditioning, insertional mutagenesis, and evolving end-organ damage.

Key Recommendations

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

Scope & Objectives

Clinical Topic

Sickle Cell Disease

Objectives

To provide standardized, evidence-informed practical recommendations for the clinical implementation of ex vivo gene therapies for sickle cell disease.

Target Patient Population

Individuals with severe sickle cell disease

Target Providers

HematologistsTransplant specialistsTransfusion medicine specialistsReproductive health providersMental health professionalsSocial service providers

Patient Criteria & Setting

Therapeutic Area

Hematology

Guideline Scope

TreatmentManagement

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

Inpatient hospitalOutpatient clinicApheresis center

Special Populations

AdolescentsAdultsPatients with α-thalassemia trait

Safety & Contraindications

Contraindications

  • Granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization

Monitoring Guidance

Annual surveillance beginning 1-2 years after treatment and lasting up to 15 years, conceptualized across late effects of conditioning, risks related to gene modification (insertional mutagenesis), and evolution of SCD-related organ damage.

Authors & Contributors

Akshay SharmaAdetola KassimAlexis ThompsonDavid A. WilliamsHien D. LiuJaap J. BoelensJames L. LaBelleJohn TisdaleJosu de la FuenteJulie KanterLakshmanan KrishnamurtiLydia H. PeckerMark C. WaltersMary EapenMatt PorteusMonica BhatiaSandeep SoniSelim CorbaciogluTami D. JohnMaría I. Cancio

Guideline Features

Dosing informationFlowcharts includedMultidisciplinary

Learning Context

Difficulty

advanced

Learning Paths

Sickle Cell DiseaseGene TherapyCellular TherapyHematologyStem Cell TransplantApheresisPharmacokineticsFertility Preservation