Aplastic anemia (AA) is a rare and serious blood disorder characterized by the failure of the bone marrow to generate new blood cells. Although AA is severe and affects blood-forming tissue, it is not a cancer. It is classified as a syndrome separate from malignancies like leukemia.
Aplastic Anemia Classification A Bone Marrow Failure Disorder
The fundamental difference between aplastic anemia and cancer lies in the underlying cellular activity within the bone marrow. Cancers of the blood, such as leukemia, are defined by an uncontrolled and abnormal overproduction of defective white blood cells, a process called malignancy. These abnormal cells crowd out the healthy blood-forming elements in the marrow.
In contrast, aplastic anemia is characterized by hypoproduction, where the bone marrow is severely underactive. The tissue becomes hypocellular, with the normal blood-forming hematopoietic stem cells being replaced by fat cells. The term “aplasia” refers to this absence of cell development.
This failure of production leads to pancytopenia, a deficiency in all three main blood cell lines. Patients exhibit low counts of red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia). These deficiencies cause fatigue, increased infection risk, and easy bruising or bleeding.
Diagnosis typically involves a bone marrow biopsy, where a sample of the spongy tissue is examined. A diagnosis of aplastic anemia is confirmed when the biopsy shows a markedly hypocellular marrow, often with cellularity below 25%. This finding helps distinguish AA from malignancies, which typically show hypercellularity or an infiltration of abnormal cells.
Understanding the Immune System Attack
Most cases of aplastic anemia are acquired, meaning they develop during a person’s lifetime. The primary mechanism driving acquired aplastic anemia is an autoimmune attack directed against the body’s own bone marrow stem cells. This attack destroys the stem cells responsible for generating all mature blood cells, causing the marrow to become hypocellular.
This destructive process is carried out primarily by activated cytotoxic T-lymphocytes, a type of white blood cell. These T-cells mistakenly identify the hematopoietic stem cells as foreign invaders and launch an attack. The T-cells release high levels of inflammatory signaling molecules, such as interferon-gamma.
Interferon-gamma is a cytokine that suppresses blood cell formation and induces the programmed death, or apoptosis, of the stem cells. While inherited forms of AA, such as Fanconi anemia, exist, the acquired, immune-mediated form is the most common presentation and guides most current treatment strategies.
Primary Treatment Pathways
Because acquired aplastic anemia is fundamentally an immune-mediated disease, treatment focuses on either halting the autoimmune attack or replacing the damaged bone marrow. The choice between the two main strategies depends on the patient’s age and the availability of a suitable donor.
Immunosuppressive Therapy (IST)
Immunosuppressive Therapy (IST) is a common first-line treatment, especially for older patients or those without a matched donor. This therapy uses powerful drugs to suppress the aggressive T-cells attacking the bone marrow. A typical regimen involves the combination of Antithymocyte Globulin (ATG) and cyclosporine. ATG is an antibody preparation that targets and eliminates the T-cells, while cyclosporine helps prevent the remaining T-cells from becoming activated. The goal of IST is to dampen the immune response, allowing surviving stem cells to recover and resume normal blood cell production.
Hematopoietic Stem Cell Transplantation (HSCT)
The other curative treatment option is Hematopoietic Stem Cell Transplantation (HSCT), often referred to as a bone marrow transplant. This procedure involves replacing the patient’s failed bone marrow with healthy stem cells from a donor. HSCT is generally the preferred approach for younger patients who have a suitable matched sibling donor, as it offers the highest potential for a permanent cure.