Initial Immunosuppressive Treatment for Aplastic Anemia
The first-line immunosuppressive therapy for aplastic anemia is horse antithymocyte globulin (ATG) plus cyclosporine A (CSA), especially for patients who are not candidates for allogeneic stem cell transplantation. 1
Patient Selection for Immunosuppressive Therapy
Immunosuppressive therapy is most appropriate for:
- Patients without an HLA-matched sibling donor
- Patients generally aged <60 years
- Patients with <5% marrow blasts
- Patients with hypocellular bone marrow
- Patients with PNH clone positivity
- Patients with STAT-3 mutant cytotoxic T-cell clones 1
Standard Immunosuppressive Regimen
The standard immunosuppressive protocol consists of:
- Horse ATG: 40 mg/kg/day for 4 days 2, 3
- Cyclosporine A: 10-12 mg/kg/day for 6 months (adjusted for blood levels) 2, 3
- Short course of corticosteroids: Often included to mitigate ATG-related serum sickness 3
Expected Outcomes
- Response rates: 60-67% at 3 months, with up to 78% responding by 1 year 2, 3
- Survival: Actuarial survival of 86% at 1 year and 72% at 2 years 2
- Relapse risk: Approximately 36% actuarial risk at 2 years, but most relapsed patients respond to additional courses of immunosuppression 2
Monitoring and Follow-up
- Weekly complete blood counts with differentials until stable platelet count is achieved
- Monthly CBCs with differentials thereafter
- Monitor for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and other viral infections
- Screen for paroxysmal nocturnal hemoglobinuria (PNH) clones 1
Treatment Alternatives and Adjuncts
For patients who fail to respond to initial ATG plus CSA:
- Second course of immunosuppression: Consider rabbit ATG plus cyclosporine and cyclophosphamide 1
- Eltrombopag: Can be considered for refractory patients, particularly for severe thrombocytopenia 1, 4
- Allogeneic stem cell transplantation: Consider for eligible patients who fail immunosuppressive therapy 5
Potential Complications and Management
- Serum sickness: Common with ATG; manage with corticosteroids
- Infections: Prophylactic antimicrobials may be needed during severe neutropenia
- Evolution to other hematologic diseases: Monitor for development of myelodysplastic syndrome (MDS), acute leukemia, or PNH 2, 3
Important Considerations
- All blood products for transfusion should be irradiated and filtered 1
- HLA typing should be performed early to evaluate for potential bone marrow transplantation if the patient is a candidate 1
- Early response (within 3 months) is associated with better long-term survival 3
- Relapse does not significantly influence overall survival 3
Immunosuppressive therapy with horse ATG plus cyclosporine remains the standard of care for patients with aplastic anemia who are not candidates for allogeneic stem cell transplantation, with demonstrated efficacy in achieving hematologic improvement and long-term survival.