What is the recommended dose of Anti-Thymocyte Globulin (ATG) for aplastic anemia?

Recommended Dose of Anti-Thymocyte Globulin (ATG) for Aplastic Anemia

For aplastic anemia, the recommended dose of ATG is 10-15 mg/kg/day for 4-5 days when using horse ATG (ATGAM), or 40 mg/kg/day for 4-5 days when using rabbit ATG (ATG-F). The specific dosing depends on the transplantation setting and ATG formulation being used.

ATG Dosing by Transplantation Type

For Hematopoietic Stem Cell Transplantation (HSCT)

1. HLA-matched sibling transplantation:

   • Cy-ATG regimen: ATG 11.25-15.00 mg/kg total, administered on days -5 to -2 1
   • Cyclophosphamide 200 mg/kg is given concurrently

2. Unrelated donor transplantation:

   • FluCy-ATG regimen: ATG 11.25-15.00 mg/kg total, administered on days -5 to -2 1
   • Combined with Fludarabine 120 mg/m² and Cyclophosphamide 120 mg/kg

3. Haploidentical transplantation:

   • ATG 10 mg/kg total, administered on days -5 to -2 2, 1
   • Or ATG-F (rabbit) 40 mg/kg total, administered on days -5 to -2 2

For Immunosuppressive Therapy (IST)

When HSCT is not feasible, immunosuppressive therapy with ATG is the alternative:

• Standard dosing: ATG 40 mg/kg/day for 4 days (total 160 mg/kg) 1
• Lower-dose option: ATG 15 mg/kg/day for 5 days (total 75 mg/kg) 3

Formulation Considerations

1. Horse ATG (ATGAM/Thymoglobuline):

   • Standard dose: 40 mg/kg/day for 4 days
   • Lower dose options: 15-25 mg/kg/day for 4-5 days 3, 4

2. Rabbit ATG (ATG-F/Fresenius):

   • Standard dose: 40 mg/kg total, administered over 4 days 2

Efficacy and Safety Considerations

• Lower-dose ATG regimens (15 mg/kg/day for 5 days) have shown similar response rates and survival outcomes compared to standard-dose regimens in some studies 3
• However, very low doses (5 mg/kg/day or less) have demonstrated poor efficacy 5, 6
• The Chinese Society of Hematology recommends ATG at 10 mg/kg over 4 days (days -5 to -2) or ATG-F at 40 mg/kg over the same period for various transplantation protocols 2

Important Clinical Considerations

• ATG should always be administered with cyclosporine (10-12 mg/kg/day) for optimal outcomes
• Premedication with corticosteroids, antihistamines, and antipyretics is essential to prevent infusion reactions
• Close monitoring for serum sickness, infections, and other complications is required
• Response evaluation should be performed at 3,6, and 12 months after treatment
• For non-responders to initial IST by 6 months, consider a second course of ATG (different preparation) or alternative donor HSCT

The choice between standard and lower-dose ATG regimens may be influenced by patient factors such as age, comorbidities, and resource constraints, but the evidence suggests that the recommended doses above provide the optimal balance of efficacy and safety for most patients with aplastic anemia.