What are the causes and treatment options for red cell aplasia?

Causes and Treatment of Red Cell Aplasia

Pure red cell aplasia (PRCA) is caused by various conditions including viral infections (especially parvovirus B19), thymoma, lymphoproliferative disorders, autoimmune diseases, drugs, and erythropoietin antibodies, with treatment directed at the underlying cause and often requiring immunosuppressive therapy.

Definition and Characteristics

PRCA is characterized by:

• Severe normocytic anemia with profound reticulocytopenia (<10×10^9/L)
• Near-complete absence of erythroid precursors in bone marrow
• Normal white blood cell and platelet counts
• Transfusion dependence in many cases

Classification of PRCA

Congenital PRCA

• Diamond-Blackfan anemia (inherited ribosomopathy)

Acquired PRCA

Primary (Idiopathic)

• No identifiable underlying cause

Secondary PRCA

1. Infectious causes:

   • Parvovirus B19 (most common infectious cause) 1
   • Other viral infections

2. Neoplastic associations:

   • Thymoma (requires thymectomy but with limited success) 1
   • Large granular lymphocyte leukemia
   • Lymphoproliferative disorders
   • Myelodysplastic syndromes (MDS)
   • Chronic myelomonocytic leukemia (CMML) 2

3. Autoimmune disorders:

   • Systemic lupus erythematosus
   • Rheumatoid arthritis

4. Drug-induced PRCA:

   • Erythropoietin-stimulating agents (ESAs) - antibody-mediated 3, 4
   • Chloramphenicol (can cause irreversible bone marrow depression) 5
   • Immunosuppressants
   • Anticonvulsants

5. Immune checkpoint inhibitor-associated PRCA 3

Diagnostic Approach

1. Initial evaluation:

   • Complete blood count with reticulocyte count
   • Peripheral blood smear
   • Bone marrow aspiration and biopsy with iron stain

2. Secondary cause investigation:

   • Parvovirus B19 PCR
   • Chest imaging to evaluate for thymoma
   • Autoimmune disease markers
   • Medication review
   • Anti-erythropoietin antibody testing (if on ESA therapy)
   • Evaluation for lymphoproliferative disorders

Treatment Strategies

1. Treat Underlying Cause

• Parvovirus B19 infection: Intravenous immunoglobulin (IVIG) 1
• Thymoma: Surgical thymectomy (mandatory but limited success rate) 1
• Drug-induced PRCA: Discontinue offending medication
  • For ESA-induced PRCA: stop all ESA therapy immediately 3
• Lymphoproliferative disorders: Treat the primary malignancy

2. Immunosuppressive Therapy

For idiopathic PRCA or when underlying cause treatment is insufficient:

• First-line therapy:

  • Corticosteroids alone provide limited sustained responses 1
  • Cyclosporine A (target blood levels 150-250 ng/mL) - highest response rate 1, 6

• Second-line options:

  • Cyclophosphamide (particularly effective in large granular lymphocyte leukemia) 1
  • Sirolimus (mTOR inhibitor) for refractory cases 6
  • Rituximab 3

3. Supportive Care

• Red blood cell transfusions for symptomatic anemia
• Iron chelation therapy if receiving >20 units of blood 1
• Monitor for and treat infections in immunosuppressed patients

4. Advanced Options

• Allogeneic stem cell transplantation for refractory cases 6
• Roxadustat for anti-erythropoietin antibody-mediated PRCA 6

Special Considerations

1. ESA-induced PRCA:

   • More common with subcutaneous administration
   • Requires immediate discontinuation of all ESAs
   • Anti-erythropoietin antibodies must be undetectable before considering reintroduction 3

2. MDS-associated PRCA:

   • May respond to immunosuppressive therapy similar to aplastic anemia
   • Consider hypomethylating agents (azacitidine, decitabine) 3

3. Monitoring during treatment:

   • Regular blood counts and reticulocyte monitoring
   • Therapeutic drug monitoring for cyclosporine
   • Vigilance for opportunistic infections during immunosuppression

4. Caution in CMML with PRCA:

   • Immunosuppressive therapy may accelerate leukemic transformation 2

The treatment goal is to achieve transfusion independence while managing the underlying condition and minimizing complications from both the disease and therapy.