Aplastic Anemia Treatment

This information represents the views of the doctors and nurses serving on the American Cancer Society's Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

Treatment for aplastic anemia is either primary or supportive. Primary treatment is aimed at curing the disease. Common primary treatments are stem cell transplant and immune suppression. Supportive treatment is aimed at helping the symptoms of aplastic anemia without actually trying to cure it. Treating anemia with transfusions is a type of supportive treatment.

Primary treatment

Allogeneic stem cell transplant

Allogeneic stem cell transplant is considered the best treatment for younger people with aplastic anemia. Transplantation works best in children and young adults. As people get older, it's harder for them to tolerate this procedure. For people older than 30 or 40, many doctors prefer using immune therapy as the first treatment. In order for transplant to be an option, you need to have a donor who is matched to you. Someone who is closely related to you, like a brother or sister, is generally the best choice. In aplastic anemia, this stem cell transplant is successful up to 80% to 90% of the time if cells from a matched related donor are used.

Matching is determined by a type of test called HLA typing, which is done in the laboratory. If there is no match from a brother or sister, sometimes an unrelated donor will match. A transplant from a matched-unrelated donor is riskier than using a sibling match. Another option is to use stem cells from the umbilical cord of a newborn baby. A nationwide registry of potential stem cell donors and stored umbilical cord blood has been developed (www.marrow.org). Many doctors recommend using a non-related donor only if immune treatments described below don't work.

For a stem cell transplant, you will first receive chemotherapy. The chemotherapy drugs used most often include cyclophosphamide (Cytoxan®) and fludarabine (Fludara®). A drug to suppress your immune system, like anti-thymocyte globulin (ATG) or alemtuzumab (Campath®), is also given. A newer drug, daclizumab (Zenapax®), may also be used. This immune treatment is important to keep your immune system from killing the new bone marrow (like it killed your original bone marrow). Immune treatment is also important to prevent the new bone marrow from attacking your body (this is called graft-versus-host disease and is discussed later in this section). You may also get a low dose of radiation therapy to your whole body.

Soon after the radiation and/or chemotherapy, you will receive a transfusion with blood-forming stem cells from a donor. The stem cells can be obtained from the donor by removing bone marrow in the operating room while he or she is under general anesthesia. Sometimes a procedure called apheresis is used to remove stem cells from the bloodstream. Apheresis uses a machine that is hooked up to a large vein (through a catheter) and removes stem cells from the blood (returning the other cells). No matter which way they are collected, the stem cells are infused through your vein into the blood and then travel to the bone marrow, where they will grow

Stem cell transplantation is a major procedure with many risks and side effects. Some people may die during this procedure. The most serious side effects often occur during the first few weeks after the transplant. But with advances in this treatment, death from these early side effects is less common. The chance of severe side effects increases with the age of the patient.

In the first few weeks after the transplant there are usually side effects from the chemotherapy or radiation therapy. Very low blood counts requiring red blood cell and platelet transfusions are common. You may develop nausea, vomiting, diarrhea, and mouth sores from the treatment. Serious infections can also occur and are treated with large doses of antibiotics. These all generally go away in 3 to 4 weeks when the transplanted blood-forming stem cells start to produce normal blood cells. If ATG is used, there is also a risk of serious allergic reactions during the infusion. These reactions can range from skin rashes to low blood pressure and problems breathing. Generally, these side effects can be controlled with medicines. This is discussed in more detail in the next section.

A very serious side effect of a stem cell transplant is graft-versus-host disease (GVHD). This occurs when the transplanted donor cells attack your own cells through an immune reaction. GVHD is more common with unrelated or mismatched donors. The risk of GVHD is also higher in older patients. GVHD can occur very early after the transplant. This is called acute GVHD. When GVHD develops later on or lasts a long time it is called chronic GVHD. Early signs of GVHD include skin rashes with severe itching and bowel disturbances such as diarrhea. There may be abnormal lab tests showing liver damage. GVHD is treated with medications (like prednisone, methotrexate, or tacrolimus) to try to suppress the immune system. In some cases, GVHD goes away and the medications can be stopped. In other cases, GVHD is only partly controlled, and medications are needed for a long time. GVHD can sometimes be very disabling and occasionally even cause death.

For more information, please see our document, Bone Marrow and Peripheral Blood Stem Cell Transplants.

Immunosuppressive therapy

If you are not able to have a transplant (because of age or because you do not have a matched donor), doctors will recommend immunosuppressive treatment. Most cases of acquired aplastic anemia are caused by the immune system attacking the bone marrow. This treatment helps stop the immune system from killing the bone marrow cells. This type of treatment is not usually helpful for cases of inherited aplastic anemia because they are not caused by the immune system.

The major drugs used are antithymocyte globulin (ATG) and cyclosporine. ATG contains antibodies against human T-lymphocytes. This medicine is given in the hospital through an intravenous (IV) line. ATG decreases (suppresses) your immune system function by lowering the number of T-cells in the body. The antibodies in ATG come from an animal (like a horse or a rabbit), so there is a risk of a serious allergic reaction when the ATG is given. Sometimes patients getting ATG also receive a corticosteroid medicine (like prednisone) to reduce the chance that a serious reaction will occur. A newer drug, alemtuzumab (Campath®), is sometimes used instead of ATG. It has a lower risk of serious allergic reactions, but doctors aren't sure that it works as well as ATG. Often the drug called cyclosporine is given as well. This drug suppresses the immune system. Combining ATG and cyclosporine improves the blood counts in about 70% of patients with the most severe disease. The aplastic anemia may not actually be cured in most of these patients. Still, even when the blood counts do not become completely normal, they often improve enough for the patient to feel well and live a normal life. Often, after a period of remission, the aplastic anemia will come back. Usually, it will respond again to immune treatment, which can be safely repeated.

Some doctors now also give a drug called G-CSF along with ATG and cyclosporine. This drug is a growth factor for white blood cells -- it tells the bone marrow to make more of these cells. It is also known as filgrastim or Neupogen. Studies looking to see if G-CSF is helpful when given with immune therapy are ongoing.

Using high doses of cyclophosphamide (Cytoxan®) for immunosuppression is controversial. Cyclophosphamide is a chemotherapy drug that can suppress the immune system and damage T-lymphocytes. Although this treatment can be effective, many experts believe that it is more dangerous than ATG. Most doctors in the United States prefer to delay using cyclophosphamide until ATG and cyclosporine are no longer working.

Immunosuppressive therapy can have serious side effects. Holding back the immune system impairs the body's ability to fight infection. People on immunosuppression can get life-threatening infections with bacteria, viruses, and fungi. The drugs used in this therapy also have serious side effects. For example, ATG can cause serious allergic reactions with symptoms including skin rashes, low blood pressure, and problems breathing. Generally, these side effects can be controlled with medicines. Also, about 15% of patients develop leukemia or myelodysplasia several years after getting ATG. Myelodysplasia is a disorder of the bone marrow that is similar to leukemia (see the American Cancer Society document, Myelodysplastic Syndromes). Side effects of cyclosporine include high blood pressure as well as kidney and liver damage. To help prevent these problems, the doctor will check the level of cyclosporine in the blood regularly. Blood tests will also be done to check kidney and liver function. Corticosteroids (like prednisone) can cause increases in blood sugar (like diabetes), high blood pressure, weight gain, changes in mood, and weak bones.

Supportive treatment

Transfusion

While your blood counts are low, you may need transfusions of red blood cells or platelets. Although blood transfusions are generally safe, their long-term use creates problems. The main problem is that the red cells contain iron. The transfused cells only live a few weeks and iron from these cells builds up in the body. Eventually this will result in a high level of body iron, which is toxic. Although this can be treated with drugs, these aren't always successful and some organs, mainly the liver and heart, can become damaged. Also, getting tranfusions before a stem cell transplant increases the chance that the transplant won't work. This is why doctors avoid giving transfusions when a transplant is planned.

Antibiotics

Because of your low white blood cell count, you may develop an infection and need antibiotics. Infection is the major cause of death from aplastic anemia. Treatment with antibiotics should be started as soon as infection is suspected. Transfusing white blood cells is not generally practical. They survive only a very short time, and it is not possible to get enough white blood cells from normal donors to raise a person's white blood cell count.

Growth factors

Drugs can be given to increase the white blood cell count. These are called filgrastim (also called G-CSF or Neupogen®), pegfilgrastim (Neulasta®), and sargramostim (also called GM-CSF or Leukine®). These work only slightly for most patients with aplastic anemia.

Androgens

Some patients with early or mild aplastic anemia can be treated with androgens (instead of stem cell transplantation or ATG). Androgens are often the first treatment given to patients with inherited forms of aplastic anemia (like Fanconi anemia and dyskeratosis congenita). Androgens are male sex hormones that also stimulate blood production. They are the reason that men have higher red blood cell counts than do women. Although they can be effective in improving blood counts, they do not cure aplastic anemia. Also, using androgens for a long time has been linked to liver tumors and liver cancer. Androgens are male hormones, so women taking this medicine can develop masculine characteristics such as facial hair, balding, deepening voice, etc.

General considerations in treating aplastic anemia

Many years ago, aplastic anemia was considered a fatal disease unless the patient recovered without treatment (spontaneously). Now that we understand this is often an immune disease, treatments have been devised that have a high success rate.

Children with inherited causes of aplastic anemia are treated with supportive therapy (such as androgens) and stem cell transplant. Immunosuppressants don't help these patients.

Those with acquired aplastic anemia are treated with supportive care, followed by immunesuppressant therapy or stem cell transplant. Stem cell transplant is preferred when the patient has a matched, related donor, and is young and otherwise healthy. Immune treatments may be the first option for older patients and those without a matched donor.

A small number of people with aplastic anemia will develop leukemia or other cancers after several years. But it isn't clear if this is caused by the treatment, or just part of the disease itself. For example, many people with Fanconi anemia who don't get aplastic anemia, will still go on to develop leukemia.

Aplastic anemia is rare, and treating it is very specialized, so it may best be done at a major medical center where they have experience with this disease. This is particularly true for stem cell transplants.

Sometimes the first treatment isn't successful and will need to be repeated. Often the second treatment will be effective, even if the first wasn't. Also, the treatment may be only partially effective, and the blood counts may not return to normal. In this situation, many people can still lead a normal life and not need treatment. Their blood counts, although not normal, will be high enough for a normal life.

Sometimes, none of the treatments is successful. In this case a person with aplastic anemia might want to consider taking part in a clinical trial, that is, a study of a new therapy that hasn't yet been proven successful.

Adapted in part or whole from the American Cancer Society website.