Aplastic Anemia

Aplastic anemia (AA) is the medical term for bone marrow failure. The bone marrow, a spongy tissue inside the bones, is the factory for all blood cell lines -- red cells, white cells, and platelets. These cells are critical to supplying oxygen and nourishment to other tissues and organs, fighting infection, and in clotting the blood. Typically, as old blood cells die off naturally, they are replaced by new blood cells formed in the bone marrow. In aplastic anemia, the bone marrow does not produce new cells leaving the body susceptible to organ failure, bleeding, and infection. Recently, researchers have discovered that most cases of severe aplastic anemia are autoimmune disorders in which the body's own immune system attacks tissues and organs. They believe that autoreactive or abnormal immune cells known as lymphocytes suppress blood cell production and division.
Though not a cancer, the treatment of aplastic anemia is often similar to therapies used for blood-forming malignancies such as leukemias and lymphomas. As a result, AA is most commonly treated in a cancer center.

Risk Factors

A number of environmental factors, including drugs, benzene exposure, insecticides, and viruses have been identified as causes for the immune attack that leads to aplastic anemia. However, in the majority of cases, there is no identifiable cause.

Diagnostic Tests

Severe aplastic anemia is a serious disorder requiring prompt medical attention. Physicians may want to perform a variety of tests. To diagnose aplastic anemia, physicians must examine the cells of the bone marrow and blood under a microscope. To do this they will likely perform blood and laboratory tests as well as a bone marrow aspiration and biopsy. In this test, a sample of bone marrow is removed from the hipbone with a special needle under local anesthetic. Aplastic anemia is usually characterized by markedly decreased blood cell development by the bone marrow resulting in a significant decline in circulating blood cells. The physician will check the number of blood cells, including white cells known as neutrophils, clotting cells known as platelets, and young regenerating red cells known as reticulocytes. Because of a link between hepatitis and aplastic anemia, physicians may also request a laboratory test that evaluates the level of liver enzymes. HLA-typing, a laboratory blood test, is usually performed to ensure that patients receive immune compatible blood and marrow products during treatment.

Symptoms

The most common symptoms of aplastic anemia include:

* Significant fatigue
* Shortness of breath
* Recurring infections and/or flu-like symptoms
* Bruising or bleeding easily
* Difficulty in controlling bleeding, even from very minor wounds
* The appearance of small red dots on the skin that indicate bleeding under the skin

Current Treatments

High-Dose Cyclophosphamide Research at Johns Hopkins shows that high doses of the chemotherapy drug cyclophosphamide, without bone marrow transplantation, can lead to long-lasting, complete remissions in severe aplastic anemia. High-dose cyclophosphamide can rid the body of the cells that cause aplastic anemia without destroying key blood and bone marrow-forming stem cells because these stem cells contain high levels of an enzyme called aldehyde dehydrogenase, which makes them resistant to the toxic effects of cyclophosphamide.

Dr. Robert Brodsky, director of the division of Hematology, and his colleagues in neurology and rheumatology are applying this approach in other severe autoimmune disorders including, scleroderma, myasthenia gravis, multiple sclerosis and autoimmune hematologic disorders.

Bone Marrow Transplantation
Aplastic anemia was one of the first diseases for which bone marrow transplantation was found to be effective. In this therapy, the patient's own non-functioning bone marrow is destroyed with drugs and/or radiation and replaced with donor bone marrow from a compatible donor, usually a sibling or other family member. The donor marrow is given intravenously to the patient and travels to the bone regenerating blood cells The donor marrow must match the patient's immune system in order to avoid graft rejection and other serious complications. When successful, bone marrow transplant is often a cure for aplastic anemia with few incidences of relapse. However, it is a very intensive therapy, and serious immune complications and infections are not unusual. Other non-life-threatening effects of bone marrow transplantation include sterility and temporary hair loss. Patients under age forty are the best candidates. Cure rates decline significantly in those over 40.

Drug Therapy
Bone marrow transplantation may not be an option for many patients. Age, other health-related factors, or the inability to find a HLA compatible donor may make a transplant too risky. Drug therapy with antithymocyte globulin (ATG) or antilymphocyte globulin (ALG) which stimulate the production of blood cells by suppressing the immune system, may be recommended for these patients. While drug therapy is not a cure for aplastic anemia, it may partially restore blood cell production. However, as many as 50 percent of patients relapse or develop other blood forming malignancies or disorders.

High Dose Cyclophosphamide
Johns Hopkins researchers achieved successful clinical results in patients with severe aplastic anemia by using high doses of an immunosuppressive drug called cyclophosphamide. High-dose therapy with cyclophosphamide destroys the autoreative lymphocytes but leaves healthy stem cells, the cells responsible for blood cell development, intact. After treatment with cyclophosphamide, the stem cells produce blood cells, including lymphocytes, with no autoimmune characteristics. It now appears that the therapy can cure most cases of severe aplastic anemia with very low rates of relapse and minimal side effects. Researchers at Johns Hopkins are studying the drug in other severe autoimmune disorders including, scleroderma, myasthenia gravis, multiple sclerosis and autoimmune hematologic disorders.