What is the initial treatment for aplastic anemia?

Initial Treatment for Aplastic Anemia

The initial treatment for aplastic anemia is immunosuppressive therapy (IST) with antithymocyte globulin (ATG) plus cyclosporine for patients who are not candidates for allogeneic hematopoietic stem cell transplantation. 1, 2

Patient Assessment and Treatment Selection

• Diagnosis of aplastic anemia requires bone marrow evaluation showing hypocellularity and peripheral blood cytopenias 3
• Initial workup should include:
  • Complete blood count with differential, peripheral smear, and reticulocyte count 1
  • Bone marrow aspiration and biopsy 1
  • Testing for viral infections (HIV, HBV, HCV, CMV) 1
  • HLA typing (to assess transplant eligibility) 2

First-Line Treatment Algorithm

For patients ≤40 years with an HLA-matched sibling donor:

• Allogeneic hematopoietic stem cell transplantation (HSCT) 2, 4

For patients without an HLA-matched sibling donor or >40 years:

• Immunosuppressive therapy with:
  • Horse ATG (preferred over rabbit ATG) for 4 days 1, 2
  • Cyclosporine for at least 6 months 1, 2
  • Consider adding eltrombopag (starting dose 36 mg daily) 5, 3

Immunosuppressive Therapy Details

• Horse ATG is administered at 40 mg/kg/day for 4 days 2, 4
• Cyclosporine is given at 10-12 mg/kg/day (adjusted based on blood levels) 4
• A short course of corticosteroids (methylprednisolone 1 mg/kg/day for about 2 weeks) is typically added to prevent serum sickness 4
• Response to IST typically occurs within 3-6 months 2, 4

Expected Outcomes with IST

• Response rates with combined ATG and cyclosporine range from 60-78% 2, 4
• Early response (within 3 months) is associated with better long-term survival 4
• Relapse is common (36% at 2 years) but can often be managed with additional immunosuppression 2
• Overall survival at 7 years is approximately 55% 4

Addition of Eltrombopag

• Eltrombopag has shown benefit when added to standard IST 3
• Initial dose is 36 mg orally once daily 5
• Dose adjustments are made to maintain platelet count >50 × 10^9/L 5
• Maximum dose should not exceed 108 mg daily 5
• Dose reductions are needed for patients with hepatic impairment and those of East/Southeast Asian ancestry 5

Monitoring During Treatment

• Weekly complete blood counts for at least the first month 5
• Regular liver function tests (eltrombopag can cause hepatotoxicity) 5
• Cyclosporine blood levels to maintain therapeutic range 4
• Monitor for infections, which are a common complication 3, 6

Common Complications and Management

• Febrile neutropenia occurs in >50% of patients and requires prompt antibiotic therapy 6
• Serum sickness from ATG can be prevented with corticosteroids 4
• Cyclosporine side effects include gum hypertrophy and hypertension (in approximately 1/6 of patients) 6
• Eltrombopag can cause hepatotoxicity and requires regular liver function monitoring 5

Special Considerations

• Older patients (>60 years) may benefit from dose-attenuated IST with similar response rates but fewer infectious complications 3
• Some patients may develop clonal evolution to myelodysplastic syndrome or paroxysmal nocturnal hemoglobinuria 2, 6
• Patients who fail to respond to initial IST may be candidates for alternative donor transplantation 1

Treatment Response Assessment

• Response is defined as improvement in blood counts sufficient that a patient no longer meets criteria for severe disease 2
• Complete response: normalization of all blood counts 6
• Partial response: transfusion independence but without complete normalization of counts 4
• Response assessment should be performed at 3,6, and 12 months after initiation of therapy 4