Initial Treatment for Aplastic Anemia
For patients with severe aplastic anemia who are not candidates for allogeneic hematopoietic stem cell transplantation, the initial treatment is immunosuppressive therapy combining horse antithymocyte globulin (ATG) with cyclosporine. 1
Patient Assessment Before Treatment
Diagnostic workup must include:
- Complete blood count with differential, peripheral smear, and reticulocyte count 1
- Bone marrow aspiration and biopsy to confirm diagnosis 1
- Viral infection screening including HIV, HBV, HCV, and CMV 1
- HLA typing of patient and available family members to identify potential transplant candidates early 2
Treatment Algorithm Based on Transplant Eligibility
For patients who ARE candidates for allogeneic stem cell transplantation:
- Proceed directly to transplantation if a suitable donor is available 1
- This represents definitive curative therapy and should not be delayed
For patients who are NOT transplant candidates (majority of patients):
- Initiate immunosuppressive therapy with horse ATG plus cyclosporine as first-line treatment 1
Immunosuppressive Therapy Regimen
Horse ATG dosing:
- Standard dose: 40 mg/kg/day for 4 consecutive days 3, 4
- Lower dose alternative: 25 mg/kg/day for 4 days has shown comparable efficacy in resource-constrained settings 5
- For patients of East/Southeast Asian ancestry or those with hepatic impairment, dose reduction may be necessary 6
Cyclosporine dosing:
- 10-12 mg/kg/day adjusted for blood levels 4
- Continue for at least 6 months 1, 3
- Dose adjustments based on therapeutic drug monitoring
Supportive corticosteroids:
- Methylprednisolone 1 mg/kg/day for approximately 2 weeks to mitigate serum sickness from ATG 4
Expected Response and Monitoring
Response timeline:
- Initial response assessment at 3 months: expect 60-67% response rate 3, 4
- Continued improvement through 6 months: 77% response rate 5
- Final assessment at 1 year: 78% overall response rate 3
Response is defined as:
- Blood counts no longer meeting criteria for severe disease 3, 4
- Achievement of transfusion independence 7
- Reticulocyte count or platelet count >50 × 10³/μL predicts excellent long-term survival (90% at 5 years) 4
Role of Eltrombopag in Refractory Cases
For patients with insufficient response to initial immunosuppressive therapy:
- Eltrombopag (a thrombopoietin receptor agonist) is FDA-approved for severe aplastic anemia after inadequate response to immunosuppression 6
- Initial dose: 36 mg orally once daily (18 mg for East/Southeast Asian ancestry or hepatic impairment) 6
- Titrate in 36-mg increments every 2 weeks to maintain platelet count ≥50 × 10⁹/L 6
- Maximum dose: 108 mg daily 6
- Response may take up to 16 weeks 6
Common Pitfalls and Management
Relapse considerations:
- Relapse occurs in 36% of patients at 2 years but does not significantly impact survival 3
- Most relapsed patients respond to additional immunosuppression courses 3
- Relapse should not be considered treatment failure
Infectious complications:
- More than 50% of patients develop febrile neutropenia during treatment 7
- Infection is a leading cause of mortality (31% overall mortality rate) 7
- Aggressive antimicrobial prophylaxis and early intervention are critical
Cyclosporine-related toxicity:
- Approximately one-sixth of patients develop gum hypertrophy and/or hypertension 7
- Regular monitoring and dose adjustment required
Long-term complications:
- Clonal evolution to myelodysplastic syndrome or acute leukemia is rare (approximately 2%) 3, 7
- Paroxysmal nocturnal hemoglobinuria develops in approximately 10% of patients 3
- Regular surveillance for these complications is warranted
Prognostic Factors
Factors predicting excellent outcomes:
- Early satisfaction of response criteria at 3 months (86% vs 40% 5-year survival) 4
- Robust blood count recovery (reticulocyte or platelet count >50 × 10³/μL) 4
- Shorter interval from symptom onset to treatment initiation 5
Long-term survival: