A 52-year-old man with a 6-month history of progressive pancytopenia (Hb 8.5 g/dL, WBC 1.8 × 10⁹/L, platelets 35 × 10⁹/L) has a hypocellular bone marrow with no dysplasia or fibrosis. Viral serology and metabolic workup are normal. What is the drug of choice for severe aplastic anemia?

Explanation

## Severe Aplastic Anemia: Immunosuppressive Therapy **Key Point:** Severe aplastic anemia (SAA) is characterized by pancytopenia with a hypocellular (aplastic) bone marrow. In the absence of a matched sibling donor, immunosuppressive therapy (IST) is first-line. **High-Yield:** The combination of antithymocyte globulin (ATG) + cyclosporine (CsA) is the gold-standard first-line regimen for SAA. ATG targets T lymphocytes that are believed to mediate immune destruction of hematopoietic stem cells, while CsA provides additional immunosuppression and improves response rates. ## Treatment Algorithm for Severe Aplastic Anemia ```mermaid flowchart TD A[Severe Aplastic Anemia Diagnosed]:::outcome --> B{Matched sibling donor available?}:::decision B -->|Yes| C[Allogeneic hematopoietic stem cell transplant]:::action B -->|No| D[Age <40 years?]:::decision D -->|Yes| E[Consider HSCT from unrelated donor]:::action D -->|No| F[Immunosuppressive therapy: ATG + CsA]:::action F --> G[Response assessment at 3 months]:::decision G -->|Complete/partial response| H[Continue CsA, monitor]:::action G -->|No response| I[Consider HSCT or eltrombopag + IST]:::action ``` **Clinical Pearl:** ATG is derived from horse or rabbit serum and depletes T cells. The combination ATG + CsA achieves hematologic response in 60–70% of patients. Eltrombopag (a thrombopoietin receptor agonist) can be added to IST in refractory cases or used as salvage therapy. ## Comparison of Agents | Agent | Mechanism | Role in SAA | |-------|-----------|-------------| | ATG | T-cell depletion | First-line; targets immune destruction | | Cyclosporine | Calcineurin inhibitor | First-line; enhances ATG response | | Eltrombopag | TPO receptor agonist | Salvage; improves response when added to IST | | G-CSF | Granulocyte colony-stimulating factor | Supportive only; not curative | **Warning:** G-CSF monotherapy does not address the underlying immune pathology and is not effective as monotherapy for SAA; it is used only as supportive care for infections. **Mnemonic:** **SAA-IST** = Severe Aplastic Anemia → ImmunoSuppressive Therapy (ATG + CsA) is first-line for non-transplant candidates. **Tip:** Eltrombopag has emerged as a promising addition to IST and can improve response rates, but ATG + CsA remains the standard backbone.