Aplastic Anemia: Which Treatment?

• Anemia, aplastic
• Hematopoietic stem cell transplantation
• Cyclophosphamide
• Reticulocytes
• Bone marrow transplantation

The word aplastic means “unformed”; it is derived from the Greek negative prefix a and plasso, “to form.” In aplastic anemia, blood does not form, leading to deficiencies of granulocytes, platelets, and erythrocytes and to severe clinical consequences, of which infection and bleeding are the most important. In 1935, the course of this disease was considered “progressively, inexorably, and more or less rapidly, fatal” (1). In the past 30 years, morbidity and mortality from aplastic anemia have dramatically decreased because of two effective interventions: allogeneic hematopoietic stem-cell transplantation and immunosuppression with antithymocyte globulin (or antilymphocyte globulin) and cyclosporine. Five-year survival rates are now 70% to 90%. However, clinicians face increasingly complex decisions in selecting the optimal strategy for an individual patient because short-term toxicity, the rapidity and completeness of hematologic recovery, and late complications must be considered.

In this issue, Brodsky and colleagues (2) report a third option for initial treatment of aplastic anemia. They treated 19 patients with high-dose cyclophosphamide (50 mg/kg of body weight for 4 days), which is routinely used as a preparative regimen before transplantation, but did not provide allogeneic hematopoietic stem cells. Survival at 2 years was 84%. Although the study was small and uncontrolled, the data are provocative.

In aplastic anemia, reticulocytes are decreased or absent, and hematopoietic cells generally account for less than 10% to 15% of the cellularity of marrow biopsy specimens. The low frequency of CD34-positive cells in the bone marrow and of progenitor cells (erythroid burst-forming units, granulocyte–macrophage colony-forming units, and long-term culture-initiating cells) suggest that hematopoietic stem cells are depleted or that their ability to differentiate is impaired. The injury to the marrow is often immunologically mediated and may involve excessive production of interferon-γ and tumor necrosis factor by activated …