Dosage of Cyclosporine and ATG in Aplastic Anemia
For treating aplastic anemia, horse anti-thymocyte globulin (ATG) should be administered at 40 mg/kg/day for 4 days, while cyclosporine should be started at 5 mg/kg/day divided into two doses. 1, 2
ATG Dosing Protocol
Standard Horse ATG (ATGAM) Dosing:
- 40 mg/kg/day for 4 days (total dose 160 mg/kg) 1, 2
- Administer intravenously over at least 4 hours 2
- Use an in-line filter with pore size of 0.2 to 1.0 micron for all infusions 2
- Monitor for signs and symptoms of anaphylaxis during infusion and for at least 24 hours after infusion 2
Alternative ATG Dosing Options:
- Lower-dose ATGAM regimen: 15 mg/kg/day for 5 days (total dose 75 mg/kg) has shown similar response rates and survival outcomes compared to standard dosing 3
- For patients who cannot access or afford standard dose ATGAM, a dose of 25 mg/kg/day for 4 days has also demonstrated efficacy 4
- Rabbit ATG alternative: 3.5 mg/kg/day for 5 days (or 2.5 mg/kg/day for patients ≥55 years) 5
Cyclosporine Dosing Protocol
Standard Dosing:
- Initial dose: 5 mg/kg/day divided into two equal doses 1, 5
- Target blood level: 200-400 μg/L 6
- Duration: Continue for 6 months or longer based on response 5
- For patients who cannot afford standard dosing, a lower dose of 6 mg/kg/day in two divided doses has shown efficacy 7
Monitoring During Cyclosporine Therapy:
- Blood pressure measurement at each visit 8
- Serum creatinine, complete blood count, liver function tests 8
- Potassium and lipid levels 8
- Adjust dose based on blood levels and renal function 8
Combination Therapy Protocols
For HLA-Matched Sibling Transplantation:
- Cy-ATG regimen: Cyclophosphamide 200 mg/kg total dose (days -5 to -2) plus ATG 11.25-15 mg/kg (days -5 to -3 or -2) 1
For Unrelated Donor Transplantation:
- FluCy-ATG regimen: Fludarabine 120 mg/m² (days -5 to -2), Cyclophosphamide 120 mg/kg (days -5, -2), ATG 11.25-15 mg/kg (days -5 to -3 or -2) 1
For Haploidentical Transplantation:
- mBuCyFluATG regimen: Busulfan 6.4 mg/kg IV (days -7 to -6), Fludarabine 120 mg/m² (days -10 to -7), Cyclophosphamide 200 mg/kg (days -6 to -3), ATG 10 mg/kg or ATG-F 20 mg/kg (days -4 to -1) 1
Response Assessment and Follow-up
- Evaluate hematological response at 3 and 6 months after initiation of therapy 4, 5
- Overall response rates with standard ATG plus cyclosporine range from 58% at 3 months to 77% at 6 months 4
- Median time to response is approximately 93 days (range 77-139 days) 5
- Consider alternative therapy if no response is observed after 6 months 1
Common Side Effects and Management
- ATG-related: fever, chills, erythematous or urticarial rash, serum sickness (occurs in most patients within 6-18 days), thrombocytopenia requiring platelet transfusions 2
- Cyclosporine-related: hypertension, nephrotoxicity, hirsutism, gum hypertrophy 1
- For nephrotoxicity: reduce cyclosporine dose by 25-50% if serum creatinine increases >30% above baseline 8
- For hypertension: decrease cyclosporine dose and consider calcium channel blockers if needed 8
The combination of ATG and cyclosporine remains the standard immunosuppressive therapy for patients with aplastic anemia who are not candidates for bone marrow transplantation, with established efficacy and survival benefit 1, 2.