What is the appropriate management and treatment for a patient with suspected aplastic anemia?

Management of Aplastic Anemia

For newly diagnosed severe aplastic anemia, hematopoietic stem cell transplantation from an HLA-identical sibling donor is the first-line treatment for all pediatric patients and adults under age 40, while immunosuppressive therapy with horse antithymocyte globulin plus cyclosporine A is the standard for patients without a matched donor or those over 40 years. 1, 2, 3

Immediate Diagnostic Workup

The following must be obtained urgently to confirm diagnosis and guide treatment:

• Complete blood count with differential and reticulocyte count to document pancytopenia and assess severity 1
• Bone marrow biopsy and aspirate showing hypocellularity with fat replacement and absence of malignant cells 1, 2
• Peripheral blood smear to exclude dysplastic features and rule out hypoplastic myelodysplastic syndrome 1
• Cytogenetic analysis and flow cytometry to distinguish aplastic anemia from hypoplastic MDS or leukemia 1
• Viral studies (hepatitis, HIV, EBV, CMV, parvovirus B19) and nutritional assessments (B12, folate) to identify secondary causes 1
• History focusing on: radiation/toxin exposure, recent viral infections, medications, lymphocyte-depleting therapies, and family history of autoimmune disease or bone marrow failure 1

Severity Classification

Severity determines treatment urgency and approach 1:

• Severe aplastic anemia: Bone marrow cellularity <25% AND at least 2 of: ANC <0.5 × 10⁹/L, platelets <20 × 10⁹/L, reticulocytes <20 × 10⁹/L
• Very severe: Same as severe but ANC <0.2 × 10⁹/L
• Moderate: Does not meet severe criteria but has cytopenias

Treatment Algorithm Based on Age and Donor Availability

For Pediatric Patients and Adults <40 Years with HLA-Matched Sibling Donor

Proceed immediately to allogeneic hematopoietic stem cell transplantation as this provides the best long-term survival and cure 1, 2, 3, 4. The optimal conditioning regimen consists of:

• Cyclophosphamide plus antithymocyte globulin 3
• Bone marrow (not peripheral blood) as stem cell source 3
• GVHD prophylaxis with cyclosporine A and methotrexate 3

For Patients Without Matched Sibling Donor or Age >40 Years

Initiate immunosuppressive therapy with horse antithymocyte globulin (ATG) plus cyclosporine A as the standard first-line regimen 1, 2, 3. This combination achieves response rates of approximately 60-70% 2.

Consider adding eltrombopag to initial immunosuppressive therapy, as emerging evidence shows improved response rates when combined with horse ATG and cyclosporine 1, 2. Randomized studies are ongoing but early results are encouraging 2.

For Younger Patients Without Sibling Donor

Closely matched unrelated donor transplantation shows increasingly favorable outcomes and should be considered, particularly in younger patients who fail initial immunosuppressive therapy 2, 4.

Critical Supportive Care Measures

All patients require aggressive supportive care during treatment 1, 2:

• Transfusion support: Use irradiated and leukocyte-filtered blood products to prevent transfusion-associated GVHD and alloimmunization 1
• Platelet transfusions: Maintain platelets >10 × 10⁹/L prophylactically, or >20 × 10⁹/L if bleeding complications present 1
• Growth factor support: May be considered as needed, though not routinely recommended 1
• Infection prophylaxis: Essential during neutropenic periods

Monitoring During Treatment

• Weekly CBC during initial treatment phase 1
• Monitor for treatment response: Improvement in blood counts and reduction in transfusion requirements 1
• For patients on eltrombopag: Regular liver function tests and dose adjustment based on platelet response 1
• Long-term surveillance: Monitor for clonal evolution, as somatic mutations and clonal hematopoiesis occur frequently in aplastic anemia patients 2

Common Pitfalls to Avoid

Do not delay treatment while awaiting complete diagnostic workup - initiate supportive care and begin treatment planning immediately upon strong clinical suspicion 1.

Do not confuse aplastic anemia with hypoplastic MDS or acute leukemia - this leads to inappropriate treatment and worse outcomes 1. Cytogenetic analysis and flow cytometry are essential to distinguish these entities 1.

Do not use rabbit ATG as first-line therapy - horse ATG demonstrates superior response rates compared to rabbit ATG in head-to-head trials 2, 3.

Do not use peripheral blood stem cells for transplantation - bone marrow is the preferred stem cell source with better outcomes 3.

Avoid non-irradiated blood products in potential transplant candidates, as this increases risk of transfusion-associated GVHD 1.

Refractory Disease Options

For patients failing initial immunosuppressive therapy 2:

• Matched unrelated donor or haploidentical transplantation with improving outcomes
• Addition of eltrombopag to salvage regimens
• Repeat immunosuppressive therapy in select cases