What is the recommended dose of Anti-Thymocyte Globulin (ATG) per kilogram body weight for treating aplastic anemia?

ATG Dosing in Aplastic Anemia

For immunosuppressive therapy of aplastic anemia, horse ATG should be administered at 40 mg/kg/day for 4 consecutive days, combined with cyclosporine 5 mg/kg/day divided into two doses. 1

Standard Dosing Protocols

For Immunosuppressive Therapy (Non-Transplant)

• Horse ATG: 40 mg/kg/day for 4 days (total dose 160 mg/kg) is the established standard recommended by major hematology societies 1
• Cyclosporine should be initiated at 5 mg/kg/day divided into two equal doses 1
• This regimen is indicated for patients who are not candidates for allogeneic stem cell transplantation 2

For Transplant Conditioning Regimens

HLA-Matched Sibling Transplantation:

• Cyclophosphamide 200 mg/kg (total dose) plus ATG 11.25-15 mg/kg using the Cy-ATG regimen 3, 1

Unrelated Donor Transplantation:

• Fludarabine 120 mg/m² + Cyclophosphamide 120 mg/kg + ATG 11.25-15 mg/kg (FluCy-ATG regimen) 3, 1

Haploidentical Transplantation:

• Modified regimens use ATG 10 mg/kg or ATG-F (Fresenius) 20-40 mg/kg administered over days -5 to -2 or -4 to -1 3, 1
• The mBuCyFluATG regimen includes: Busulfan 6.4 mg/kg IV + Fludarabine 120 mg/m² + Cyclophosphamide 200 mg/kg + ATG 10 mg/kg 3, 1

Important Distinctions Between ATG Preparations

• Horse ATG (equine) has demonstrated superior efficacy compared to rabbit-derived ATG for aplastic anemia treatment 1
• Rabbit ATG is FDA-approved only for renal transplant rejection, not specifically for aplastic anemia 1
• When using ATG in conditioning regimens, ATG (thymoglobuline) is dosed at 10 mg/kg while ATG-F (Fresenius) is dosed at 40 mg/kg due to different potencies 3

Evidence on Lower Dose Regimens

While some studies have explored reduced dosing, the evidence is mixed:

• A study using 25 mg/kg/day × 4 days of equine ATG showed similar response rates (77% at 6 months) compared to standard 40 mg/kg/day dosing 2
• Another study using 15 mg/kg/day × 5 days demonstrated comparable response rates (71%) and survival to standard dosing 4
• However, a study using very low dose ATG at 5 mg/kg/day × 5 days showed poor efficacy with only 8% response rate in older patients 5

Despite these findings, the standard 40 mg/kg/day × 4 days remains the guideline-recommended dose because it represents the most extensively validated regimen with established efficacy and safety profiles 1.

Critical Monitoring Requirements

• Daily complete blood count monitoring during ATG initiation 1
• Monitor for serum sickness (occurs in ~10% of patients) which may cause acute renal dysfunction 1
• Watch for major adverse reactions: anaphylaxis, dyspnea, hemolysis, leukopenia, thrombocytopenia, and sepsis 1
• Pneumocystis pneumonia prophylaxis should be provided to all patients receiving ATG 1
• Monitor for pulmonary edema and systemic inflammatory response syndrome during infusion 1

Common Pitfalls to Avoid

• Do not use rabbit ATG as first-line therapy for aplastic anemia—horse ATG is superior 1
• Do not reduce the dose below 40 mg/kg/day for standard immunosuppressive therapy unless in resource-constrained settings where lower doses have been specifically validated 2, 4
• Do not confuse dosing between ATG preparations in transplant conditioning—thymoglobuline (10 mg/kg) and ATG-F (40 mg/kg) are not interchangeable 3
• Ensure adequate infection prophylaxis is in place before starting therapy 1