What is the treatment for aplastic anemia?

Treatment of Aplastic Anemia

For newly diagnosed severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin (ATG) plus cyclosporine is the first-line treatment for patients without an HLA-identical sibling donor, while allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling is preferred for patients under age 40 who have a matched sibling donor. 1, 2

Initial Diagnostic Workup

Before initiating treatment, complete the following essential assessments:

• Complete blood count with differential, peripheral smear, and reticulocyte count 1
• Bone marrow aspiration and biopsy to confirm hypocellularity and exclude other diagnoses 1, 3
• Viral infection screening including HIV, HBV, HCV, and CMV 1
• HLA typing of patient and available first- and second-degree family members to identify potential transplant donors 1

Treatment Algorithm Based on Patient Characteristics

For Patients WITH an HLA-Identical Sibling Donor

Allogeneic hematopoietic stem cell transplantation is the preferred first-line treatment for patients younger than 40 years with severe aplastic anemia who have an HLA-identical sibling donor. 2, 4

Optimal transplant conditioning consists of:

• Cyclophosphamide plus antithymocyte globulin 2
• Bone marrow (not peripheral blood) as the stem cell source 2
• Graft-versus-host disease prophylaxis using cyclosporine A and methotrexate 2

For Patients WITHOUT an HLA-Identical Sibling Donor

Immunosuppressive therapy is the first-line treatment, consisting of:

• Horse antithymocyte globulin (ATG) combined with cyclosporine 1, 2
• Cyclosporine should be continued for at least 6 months 1
• Maintain therapeutic cyclosporine levels at 200-400 ng/mL 5

For Patients Who Fail Initial Immunosuppressive Therapy

Alternative donor transplantation should be considered for patients who do not respond to initial immunosuppressive therapy. 1

Adjunctive Pharmacotherapy: Eltrombopag

Eltrombopag is FDA-approved for treatment of adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy. 6

Dosing considerations:

• Eltrombopag is indicated specifically for refractory severe aplastic anemia after immunosuppressive therapy failure 6
• This represents a second-line option, not initial therapy 6

Critical Supportive Care Measures

Transfusion Support

Implement the following transfusion thresholds:

• Platelet transfusions prophylactically when counts fall below 10 × 10⁹/L 5
• Platelet transfusions when counts are 10-20 × 10⁹/L in presence of fever or infection 5
• Target platelet counts of 30-50 × 10⁹/L minimum for active bleeding or planned procedures 5
• Red blood cell transfusions for hemoglobin <9 g/dL using restrictive thresholds 5

All blood products must be leukoreduced and irradiated to prevent transfusion-associated graft-versus-host disease and minimize alloimmunization, which is critical for future transplant success. 5

Infection Prevention and Management

For patients with severe neutropenia (ANC <100/mm³ expected for >2 weeks):

• Prophylactic fluoroquinolones should be considered 5
• Establish empirical broad-spectrum antimicrobial therapy immediately for any febrile neutropenic episodes 5
• Complete thoracic CT and abdominal imaging if fungal infection is suspected 5

Monitoring Treatment Response

Document hematologic response by monitoring:

• Complete blood counts showing improvement in at least one cell line 5
• Ensure cyclosporine levels remain therapeutic (200-400 ng/mL) throughout treatment 5

Common Pitfalls to Avoid

Critical safety considerations:

• Never discharge patients with uncontrolled bleeding or platelet counts <30 × 10⁹/L without a clear transfusion support plan 5
• Do not prematurely discontinue antimicrobial prophylaxis in severely neutropenic patients (ANC <500/mm³) 5
• Avoid single-unit transfusion policy violations; use leukoreduced and irradiated products exclusively 5
• Do not delay HLA typing—this must be completed at diagnosis to avoid treatment delays 1

Expected Outcomes

With appropriate treatment, more than 75% of newly diagnosed patients (higher percentage in younger patients) become long-term survivors. 2 The key to achieving these outcomes is prompt diagnosis, immediate initiation of appropriate first-line therapy based on donor availability and patient age, and meticulous supportive care to prevent life-threatening complications during the pancytopenic phase.