What is the initial treatment for aplastic anemia?

Initial Treatment for Aplastic Anemia

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

Diagnostic Workup Before Treatment

• A complete diagnostic evaluation is essential before initiating treatment, including:
  • Complete blood count with differential, peripheral smear, and reticulocyte count 1
  • Bone marrow aspiration and biopsy to confirm the diagnosis 1
  • Testing for viral infections (HIV, HBV, HCV, CMV) 1

First-Line Treatment Algorithm

For Patients Not Eligible for Stem Cell Transplantation:

• Standard Immunosuppressive Therapy:

  • Horse ATG at appropriate dosing for 4 days 1, 2
  • Cyclosporine administered for at least 6 months (adjusted for blood levels) 1, 2
  • Short course of corticosteroids may be added to the regimen 3

• Monitoring Response:

  • Response rates with this combination therapy are approximately 60-78% at 3-12 months 2, 3
  • Early response (within 3 months) is associated with better long-term survival 3

For Refractory Severe Aplastic Anemia:

• Eltrombopag Treatment:
  • Initial dose of 36 mg orally once daily 4
  • Dose adjustments based on platelet count response 4
  • Target platelet count ≥50 x 10^9/L 4
  • Maximum dose should not exceed 108 mg per day 4
  • Dose reductions needed for patients with hepatic impairment and some patients of East-/Southeast-Asian ancestry 4

Special Considerations

• Dosing Adjustments:

  • For elderly patients (>60 years), dose-attenuated immunosuppressive therapy may be considered, as it shows similar response rates with fewer infectious complications 5
  • For patients with hepatic impairment receiving eltrombopag, initiate at a reduced dose of 18 mg once daily 4

• Monitoring During Treatment:

  • Regular monitoring of blood counts is essential during therapy 1, 4
  • Liver function tests should be monitored regularly due to potential hepatotoxicity with eltrombopag 4
  • Monitor for common adverse effects including febrile neutropenia, gum hypertrophy, and hypertension 6

• Treatment Duration and Follow-up:

  • Cyclosporine should be continued for at least 6 months 1
  • If no hematologic response occurs after 16 weeks of eltrombopag therapy, discontinue treatment 4
  • For patients who achieve tri-lineage response with eltrombopag lasting at least 8 weeks, dose may be reduced by 50% 4

Potential Complications and Management

• Relapse:

  • Relapse is common (approximately 36% risk at 2 years) but usually responds to additional courses of immunosuppression 2
  • Relapse does not significantly impact overall survival 3

• Clonal Evolution:

  • Monitor for evolution to myelodysplastic syndromes, acute leukemia, or paroxysmal nocturnal hemoglobinuria 2, 3
  • If new cytogenetic abnormalities are observed, consider discontinuation of eltrombopag 4

• Mortality Risk:

  • Most common causes of death are infections and intracranial hemorrhage 6
  • Early response to treatment is associated with significantly better survival (86% vs 40% at 5 years) 3