Clinical Scorecard: Evaluation of ATG and Alternative Serotherapy in Conditioning Protocols for Autologous HSCT in Autoimmune Disorders: Insights from the EBMT Autoimmune Diseases Working Party (ADWP)

At a Glance

Key Highlights

• Cyclophosphamide-ATG (Cy-ATG) and BEAM-ATG are the most commonly used conditioning regimens across EBMT centers.
• Thymoglobulin is the predominant ATG type used, with variable dosing and fractionated administration over multiple days.
• Serotherapy-related adverse effects include infusion reactions and disease-specific transient symptoms; premedication with antihistamines, steroids, and paracetamol is universally applied.

Guideline-Based Recommendations

Diagnosis

• HSCT is indicated for highly active relapsing-remitting multiple sclerosis failing disease modifying therapies and early severe diffuse-cutaneous systemic sclerosis.

Management

• Use of ATG as part of conditioning regimen for T-cell depletion to enhance immune resetting.
• Cyclophosphamide-ATG and BEAM-ATG regimens recommended by EBMT guidelines.
• Premedication with antihistamines, steroids, and paracetamol to prevent serotherapy-related adverse events.
• Fractionated ATG dosing over 3 to 5 days with slow infusion rates (6 to 12 hours) is standard practice.

Monitoring & Follow-up

• Monitor for infusion-associated reactions including cytokine-release syndrome, anaphylaxis, and allergic phenomena.
• Observe for disease-specific transient symptoms such as pseudo-relapse in MS, neurological worsening, cardiac toxicity and renal crises in systemic sclerosis.
• Assess completion of planned total doses of ATG and rituximab.

Risks

• Infusion-related adverse events including cytokine-release syndrome and anaphylaxis.
• Disease-specific complications during serotherapy, e.g., pseudo-relapse in neurological autoimmune diseases, cardiac and pulmonary toxicity in systemic sclerosis.
• Potential renal crises associated with steroid use in rheumatological diseases.

Patient & Prescribing Data

Adult autoimmune disease patients undergoing autologous HSCT at EBMT centers

Most centers successfully administer planned total doses of ATG; rituximab is used adjunctively in some centers. Variability exists in dosing and timing of serotherapy reflecting center preference and availability.

Clinical Best Practices

• Employ Cyclophosphamide-ATG or BEAM-ATG conditioning regimens as per EBMT guidelines.
• Use Thymoglobulin as the preferred ATG type with fractionated dosing over multiple days.
• Administer premedication with antihistamines, steroids, and paracetamol to mitigate infusion reactions.
• Monitor closely for disease-specific transient symptoms and serotherapy-related adverse events.
• Adjust serotherapy dosing and timing based on patient tolerance and center protocols.

References

• EBMT Guidelines on Autologous HSCT in Autoimmune Diseases
• Multiple Sclerosis and HSCT Standard of Care
• Systemic Sclerosis and HSCT Recommendations
• Serotherapy and ATG Use in HSCT Conditioning