Initial Treatment for Aplastic Anemia
The initial treatment for aplastic anemia should be anti-thymocyte globulin (ATG) with cyclosporine A as first-line immunosuppressive therapy for patients without an HLA-matched sibling donor, while allogeneic hematopoietic stem cell transplantation (HSCT) should be considered first-line therapy for eligible patients with an HLA-matched donor. 1
Treatment Algorithm Based on Patient Characteristics
Step 1: Confirm Diagnosis and Assess Severity
- Bone marrow aspirate and biopsy to confirm hypocellularity
- Complete blood count to determine severity (severe vs. non-severe)
- Cytogenetics to rule out myelodysplastic syndrome
Step 2: Donor Availability Assessment
- HLA typing of patient and family members should be performed immediately at diagnosis
- Search for matched unrelated donor should be initiated early if no sibling match is found
Step 3: Treatment Selection Based on Age, Donor Availability, and Comorbidities
For patients with HLA-matched sibling donor:
Age <40 years: Allogeneic HSCT is first-line therapy 2
- Conditioning with cyclophosphamide and ATG
- Bone marrow as preferred stem cell source
- GVHD prophylaxis with cyclosporine A and methotrexate 3
Age 40-50 years: Consider HSCT based on comorbidities and performance status
- Reduced-intensity conditioning may be appropriate
For patients without HLA-matched sibling donor:
First-line therapy: ATG plus cyclosporine A 1, 4
- ATG administered for 4 days
- Cyclosporine continued for at least 6 months
- Response rates of 67-78% at 1 year 4
For young patients (<50 years): Consider matched unrelated donor (MUD) or haploidentical HSCT if available quickly 5, 2
- MUD HSCT has shown comparable outcomes to matched sibling HSCT in recent studies
Monitoring and Response Assessment
- Monitor blood counts weekly initially, then less frequently based on response
- Evaluate response at 3 months and 6 months after immunosuppressive therapy
- Response defined as no longer meeting criteria for severe disease (increase in blood counts)
Management of Treatment Failure
For patients failing initial immunosuppressive therapy:
- Consider second course of ATG (preferably different source)
- Consider alternative immunosuppressive agents such as alemtuzumab 6
- Consider eltrombopag (36 mg daily, adjust to maintain platelet count >50 × 10^9/L) 7
- Re-evaluate for unrelated donor or haploidentical HSCT
Important Considerations
- Relapse is common after immunosuppressive therapy (36% at 2 years) 4
- Long-term survival is better with HSCT (69% at 15 years) compared to immunosuppressive therapy (38%) 8
- Risk of evolution to myelodysplastic syndrome or acute leukemia exists with immunosuppressive therapy
- Development of paroxysmal nocturnal hemoglobinuria is a known complication
Supportive Care During Treatment
- Transfusion support as needed (platelets, red blood cells)
- Prophylactic antibiotics for severe neutropenia
- Monitor for treatment-related toxicities (liver function, renal function)
- Avoid invasive procedures when possible due to bleeding risk
This treatment approach prioritizes interventions that have demonstrated the best outcomes for morbidity, mortality, and quality of life in patients with aplastic anemia.