Role of Cyclosporine in Aplastic Anemia
Cyclosporine is a critical component of first-line immunosuppressive therapy for severe aplastic anemia, used in combination with horse anti-thymocyte globulin (ATG) at a dose of 5 mg/kg/day divided into two doses, achieving response rates of approximately 60-70%. 1
Primary Treatment Role
Standard Immunosuppressive Regimen
Cyclosporine combined with horse ATG represents the standard immunosuppressive treatment for patients with severe aplastic anemia who lack an HLA-matched sibling donor or are over 40 years of age. 1, 2
The recommended dosing is cyclosporine 5 mg/kg/day divided into two equal doses, initiated concurrently with horse ATG at 40 mg/kg/day for 4 days. 1
This combination achieves overall hematologic response rates of 62-68% at 6 months, significantly superior to cyclosporine monotherapy. 3, 2, 4
Evidence for Combination Superiority
Horse ATG plus cyclosporine is vastly superior to rabbit ATG-based regimens, with response rates of 68% versus 37% (P<0.001) and 3-year survival of 96% versus 76% respectively. 2
Cyclosporine monotherapy at low doses (6 mg/kg/day) produces inferior results with only 41.66% response rates, demonstrating the necessity of combination therapy. 5
Addition of a third immunosuppressive agent (mycophenolate mofetil) to horse ATG/cyclosporine did not improve response rates beyond the standard 62% achieved with dual therapy. 3
Dosing and Monitoring Protocol
Initial Dosing
Start cyclosporine at 5 mg/kg/day divided into two doses, adjusting to maintain trough levels of 200-400 μg/L. 1
Continue treatment for a minimum of 6 months before assessing response. 1, 3
Required Monitoring
Monitor at each visit: blood pressure, serum creatinine, complete blood count, liver function tests, potassium, and lipid levels. 1
Measure cyclosporine trough levels regularly to maintain therapeutic range of 200-400 μg/L. 1
Dose Adjustments for Toxicity
Reduce cyclosporine dose by 25-50% if serum creatinine increases >30% above baseline. 1
For hypertension, decrease cyclosporine dose and consider adding calcium channel blockers. 1
Common side effects requiring monitoring include nephrotoxicity, hypertension, hirsutism, and gum hypertrophy. 1
Alternative ATG-Free Approaches
Eltrombopag Plus Cyclosporine
For patients without access to horse ATG or who cannot tolerate it, eltrombopag (150 mg daily, 100 mg in Asian patients) combined with cyclosporine achieves 46% response rates at 6 months. 6
This ATG-free regimen avoids infusion-related toxicities and hospitalization requirements but produces lower response rates than standard horse ATG/cyclosporine. 6
Treatment duration is 6 months with both agents, followed by cyclosporine tapering through month 24. 6
Clinical Outcomes and Limitations
Response Patterns
Hematologic responses typically occur within 6 months of initiating therapy. 3, 2
Among responders to horse ATG/cyclosporine, median survival is excellent and not reached in long-term follow-up. 3
Relapse occurs in approximately 37% of responders at a median of 389 days, with over half occurring during ongoing immunosuppression. 3
Clonal Evolution Risk
Approximately 9% of patients develop clonal evolution to myelodysplasia following ATG-based immunosuppression. 3
This risk persists despite combination therapy and represents a significant long-term complication. 3
Critical Pitfalls to Avoid
Never use rabbit ATG as first-line therapy when horse ATG is available—the difference in response (68% vs 37%) and survival (96% vs 76%) is clinically decisive. 2
Do not discontinue cyclosporine prematurely before 6 months, as response assessment requires this minimum duration. 1, 3
Avoid inadequate monitoring of renal function and blood pressure, as nephrotoxicity and hypertension are common and require dose adjustment. 1
Do not add additional immunosuppressive agents beyond horse ATG/cyclosporine, as mycophenolate mofetil failed to improve outcomes. 3