What is the initial treatment for severe aplastic anemia?

Initial Treatment for Severe Aplastic Anemia

The initial treatment for severe aplastic anemia should be immunosuppressive therapy with horse anti-thymocyte globulin (ATG) and cyclosporine for patients who are not candidates for allogeneic hematopoietic stem cell transplantation (HSCT). 1

Treatment Algorithm Based on Donor Availability and Age

• For patients with an HLA-matched sibling donor, allogeneic HSCT using the Cy-ATG conditioning regimen (cyclophosphamide 200 mg/kg and ATG 11.25-15.00 mg/kg) is recommended as first-line therapy 2, 3
• For patients without an HLA-matched sibling donor, immunosuppressive therapy with horse ATG plus cyclosporine is the standard first-line treatment 1, 4
• For patients with unrelated donors, the FluCy-ATG regimen (fludarabine 120 mg/m², cyclophosphamide 120 mg/kg, and ATG 11.25-15.00 mg/kg) is recommended if HSCT is pursued 2
• For haploidentical HSCT, either mBuCyFluATG or FluCy-ATG regimens may be used as conditioning protocols 2

Immunosuppressive Therapy Protocol

• Horse ATG should be administered at a dose of 40 mg/kg/day for 4 days 4, 5
• Cyclosporine should be administered at 10-12 mg/kg/day (adjusted for blood levels) for at least 6 months 1, 5
• A short course of corticosteroids (methylprednisolone 1 mg/day for about 2 weeks) may be added to the regimen 5

Response Assessment and Follow-up

• Response to immunosuppressive therapy should be assessed at 3 months after treatment initiation 4, 5
• Response is defined as improvement in blood counts sufficient that a patient no longer meets criteria for severe disease 4
• Early hematologic response (within 3 months) is associated with better long-term survival (86% vs. 40% at 5 years) 5
• Approximately 60-78% of patients respond to the combination of ATG and cyclosporine 4, 5

Management of Refractory or Relapsed Disease

• Relapse is common after immunosuppressive therapy (36% actuarial risk at 2 years) 4
• Most relapsed patients respond to additional courses of immunosuppression 4
• Patients who fail to respond to initial immunosuppressive therapy may be candidates for alternative donor transplantation 1
• For adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy, eltrombopag (a thrombopoietin receptor agonist) is indicated 6
• Eltrombopag should be initiated at 36 mg orally once daily and adjusted to maintain platelet count greater than 50 x 10⁹/L, not exceeding 108 mg per day 6

Considerations for HSCT vs. Immunosuppressive Therapy

• HSCT offers higher cure rates and lower risk of disease recurrence or development of clonal disorders compared to immunosuppressive therapy 3
• Recent advances in HSCT with alternative donors have improved outcomes, making it a viable option for more patients 7
• The risk of secondary myelodysplastic syndromes and acute leukemia after immunosuppressive therapy is a concern (though relatively rare at 1 of 51 patients in one study) 4
• Paroxysmal nocturnal hemoglobinuria may develop after immunosuppressive therapy (5 of 51 patients in one study) 4

Pitfalls and Caveats

• Delaying treatment can worsen outcomes; treatment should be initiated promptly once severe aplastic anemia is diagnosed 3
• HLA typing should be done at diagnosis before beginning treatment to identify potential donors 3
• Mismatched marrow infusion without proper conditioning has no effect on response or survival 8
• Invasive procedures should be avoided due to the high risk of hemorrhagic complications in severe aplastic anemia patients 2
• Eltrombopag is not indicated for the treatment of patients with myelodysplastic syndromes 6