What are the current treatment guidelines for aplastic anemia according to recent surveillance guidelines?

Surveillance Guidelines for Aplastic Anemia

Initial Diagnostic Workup and Assessment

All patients with suspected aplastic anemia require comprehensive laboratory evaluation including complete blood count with differential, peripheral smear, reticulocyte count, bone marrow aspiration and biopsy, viral studies (HIV, HBV, HCV, CMV), and cytogenetic analysis to confirm diagnosis and exclude other conditions such as hypoplastic MDS. 1, 2

Key diagnostic elements include:

• Bone marrow biopsy is essential to confirm hypocellularity and rule out infiltrative processes or dysplastic features that would suggest MDS rather than aplastic anemia 1, 2
• Viral infection screening is necessary as hepatitis-associated aplastic anemia requires specific consideration 1
• Cytogenetic analysis and flow cytometry help distinguish aplastic anemia from hypoplastic MDS, which has different treatment implications 2

Severity Grading and Risk Stratification

Disease severity determines treatment approach and is defined by specific hematologic parameters including absolute neutrophil count (ANC), platelet count, and reticulocyte count 2. This grading directly impacts whether patients proceed to transplantation versus immunosuppressive therapy.

First-Line Treatment Algorithm

For young patients with severe aplastic anemia who have an HLA-identical sibling donor, allogeneic hematopoietic stem cell transplantation is the first-choice treatment, while immunosuppressive therapy with horse anti-thymocyte globulin (ATG) plus cyclosporine represents the standard regimen for patients without a matched donor or those over age 40. 2, 3

Treatment Selection Based on Patient Characteristics:

Patients eligible for transplantation:

• Young patients with severe disease and HLA-matched sibling donor should proceed directly to allogeneic HSCT 2, 3
• This provides the only curative option with complete hematopoietic recovery 4

Patients requiring immunosuppressive therapy:

• Horse ATG combined with cyclosporine is the standard first-line immunosuppressive regimen 1, 2
• Cyclosporine should be continued for at least 6 months 1
• Therapeutic cyclosporine levels should be maintained at 200-400 ng/mL 5

Patients with insufficient response to initial immunosuppression:

• May be candidates for alternative donor transplantation 1
• Eltrombopag (a thrombopoietin receptor agonist) is FDA-approved for severe aplastic anemia patients who have had insufficient response to immunosuppressive therapy 6
• The combination of TPO-RA with immunotherapy (ATG plus cyclosporine) is highly effective and also works for secondary, drug-induced, or hepatitis-associated aplastic anemia 4

Eltrombopag Dosing for Refractory Severe Aplastic Anemia:

• Initiate at 36 mg orally once daily for most patients 6
• Reduce initial dose to 18 mg daily in patients with hepatic impairment or East-/Southeast-Asian ancestry 6
• Adjust dose to maintain platelet count >50 × 10⁹/L 6
• Do not exceed 108 mg per day 6
• Take without food or with low-calcium meal (≤50 mg calcium), at least 2 hours before or 4 hours after polyvalent cations 6

Supportive Care During Treatment

All patients require meticulous supportive care including transfusion support with irradiated and leukoreduced blood products, infection prophylaxis, and monitoring for complications. 2, 5, 7

Transfusion Management:

• Maintain prophylactic platelet transfusion threshold at <10 × 10⁹/L, or 10-20 × 10⁹/L with fever or infection 5
• For active bleeding or procedures, target platelet counts of 30-50 × 10⁹/L minimum 5
• Red cell transfusion threshold: hemoglobin <9 g/dL using restrictive strategy 5
• All blood products must be leukoreduced and irradiated to prevent transfusion-associated graft-versus-host disease and minimize alloimmunization 5
• Use single-unit transfusion policy when possible to reduce alloimmunization risk 5

Infection Prevention and Management:

• Initiate empirical broad-spectrum antimicrobials immediately for any febrile neutropenic episode 5
• Consider prophylactic fluoroquinolones for patients with expected prolonged severe neutropenia (ANC <100/mm³ for >2 weeks) 5
• Complete thoracic CT and abdominal imaging if fungal infection suspected 5
• Do not discontinue antimicrobial prophylaxis prematurely in severely neutropenic patients (ANC <500/mm³) 5

Iron Chelation:

• Monitor for iron overload in chronically transfused patients 7
• Consider chelation therapy when indicated based on ferritin levels and transfusion burden 7

Monitoring During Treatment

Weekly complete blood counts are required during initial treatment, transitioning to monthly once stable response is achieved. 2, 5

Response criteria include:

• Hematologic improvement in at least one cell line 5
• Reduction in transfusion requirements 2
• For patients on eltrombopag, regular liver function monitoring is mandatory 2, 6

Critical Pitfalls to Avoid

Do not delay treatment initiation while awaiting complete diagnostic workup, as this can be harmful in severe disease. 2

Additional critical considerations:

• Failure to distinguish between aplastic anemia and hypoplastic MDS leads to inappropriate treatment 2
• Never discharge patients with uncontrolled bleeding or platelet counts <30 × 10⁹/L without clear transfusion support plan 5
• Do not use non-irradiated blood products in potential transplant candidates 5
• Avoid premature discontinuation of antimicrobial prophylaxis in severely neutropenic patients 5