Immunosuppressive Therapy for Aplastic Anemia

Severe Aplastic Anemia Transplant Outcomes

Home > Patients and Families > Disease & Treatment > About Your Disease > Aplastic Anemia

Aplastic Anemia (Severe)

Aplastic anemia is a disease of the bone marrow. The bone marrow stops making enough red blood cells, white blood cells and platelets for the body. Any blood cells the marrow does make are normal, but there are not enough of them. Aplastic anemia can be moderate, severe or very severe. People with severe or very severe aplastic anemia are at risk for life-threatening infections or bleeding.

Aplastic anemia causes, symptoms and diagnosis

Aplastic anemia is a rare disease. About 3 out of every 1 million people in the United States get aplastic anemia each year. The disease appears more often in eastern Asian countries, where it affects about 15 out of every 1 million people. It can affect people of any age.

Causes

The bone marrow produces all of the blood cells for the body:

Red blood cells carry oxygen to all parts of your body.
White blood cells help the body fight infection.
Platelets help control bleeding.

Each blood cell lives only a certain number of days, so the body needs a steady supply. Healthy bone marrow is always making new blood cells. However, in aplastic anemia, the marrow makes a much smaller number than normal of all three types of blood cells. In very severe cases, the marrow can stop making any blood cells at all.

In most cases, doctors do not know the cause of aplastic anemia. In about 20% of patients, the disease develops from an inherited disorder, such as Fanconi anemia. Aplastic anemia may also be caused by high doses of radiation or certain chemicals or viruses. There is evidence that in many people aplastic anemia is an autoimmune disease. This means that the body's immune system is reacting against itself. The immune system attacks the bone marrow and stops it from making enough blood cells.

Symptoms

Symptoms of aplastic anemia are caused by low numbers of blood cells. The severity of a person's symptoms depends on the number of blood cells he or she has.

Low numbers of red blood cells can cause a person to feel tired or weak, be short of breath and look pale.
Low numbers of white blood cells can lead to frequent or severe infections.
Low numbers of platelets can lead to easy bleeding or bruising and tiny red spots under the skin (petechiae), or bleeding that is hard to stop.

For a person with moderate aplastic anemia, these symptoms may be mild or moderate. For a person with severe or very severe aplastic anemia, infections or bleeding can be life-threatening.

Diagnosis

To diagnose aplastic anemia, doctors look at samples of blood and bone marrow. In aplastic anemia, the numbers of red blood cells, white blood cells and platelets in the blood are all low. There are two types of samples that can be collected from the bone marrow. A bone marrow aspiration uses a needle to extract a small amount of liquid marrow. A bone marrow biopsy uses a special needle to remove an intact core of marrow. Aspirations and biopsies are both usually taken from the back of the hip bone.

In aplastic anemia, the marrow samples show low numbers of cells. The few cells that do appear are normal (not cancer cells). Based on the number of cells that appear, doctors diagnose the disease as moderate, severe or very severe aplastic anemia. Moderate aplastic anemia sometimes becomes severe over time, so doctors will watch for signs the disease is changing.

Aplastic anemia treatment options

Treatment options for aplastic anemia depend on how severe the disease is. A person with moderate aplastic anemia may not need any treatment. Instead, doctors will check blood counts regularly to watch for signs the disease is getting worse.

A person with severe or very severe aplastic anemia needs treatment as soon as possible. For severe and very severe aplastic anemia, standard treatment options (all discussed further below) include:

Supportive care to keep a patient stable until other treatment can begin or take effect.
Immunosuppressive therapy — drugs that suppress (weaken) the immune system.
Bone marrow or cord blood transplant (also called BMT).

All patients with severe aplastic anemia will need supportive care, but the only treatments that can cure the disease or manage it for the long-term are a transplant or immunosuppressive therapy. A transplant is the preferred standard treatment for many patients, while immunosuppressive therapy is the first choice for others.

Research into treatment of aplastic anemia is ongoing, so other, newer treatment options may also be available. Whichever treatment you and your doctor decide on, you may choose to be part of a clinical trial. Even standard treatments continue to be studied in clinical trials. These studies help doctors improve treatments so that more patients can have better results.

Supportive care — blood transfusions, growth factors, infection prevention

Patients with severe or very severe aplastic anemia will need supportive care. Supportive care such as blood transfusions, growth factors and infection prevention are not a cure. However, supportive care can manage symptoms until other treatments can begin or take effect.

Some people may also choose supportive care as their only treatment. People who are older or who have other health problems may be unable to tolerate stronger treatment. Other people weigh the possible risks and benefits of different treatment options and choose supportive care. Supportive care does not offer the possibility of curing or controlling severe aplastic anemia for the long-term, but it may provide a person with a higher quality of life.

Blood transfusions

People with severe aplastic anemia usually need blood transfusions.

Platelet transfusions reduce the risk of life-threatening bleeding caused by very low numbers of platelets.
Red blood cell transfusions reduce problems with being very tired and short of breath.

Transfusions are an important treatment to manage the symptoms of aplastic anemia. If you have severe aplastic anemia, your doctor will determine when you need transfusions and manage the possible risks. For patients with severe aplastic anemia, doctors try to give as few transfusions as possible to:

Limit the amount of iron that builds up in the body from red blood cell transfusions. Large amounts of iron in the body cause organ damage. Patients who need many red blood cell transfusions may receive additional treatment to remove iron from the body (iron chelation therapy).
Reduce risks the immune system will develop antibodies (immune cells) that attack transfused platelets.
Prepare for the possibility of a transplant. For patients treated with transplant, having many transfusions increases transplant risks.

In addition, it is common to treat the blood with radiation and to filter the white blood cells out of the blood before it is given in a transfusion. These steps help reduce the risks of an immune system reaction against transfused platelets and risks of a potential transplant, as well as risks of other possible complications.

If there is any chance a patient may receive a transplant, the doctor will avoid giving the patient blood donated by a family member. If that family member is later found to be a suitable donor for a transplant, the patient's immune system may react against the transplant.

Growth factors

Growth factors are drugs that help the body make more blood cells. A person with aplastic anemia may be given growth factors to try to reduce the need for red blood cell transfusions. However, in many cases of aplastic anemia, the marrow does not respond to growth factors.

Growth factors may also be given after treatment with immunosuppressive therapy or transplant. In this case, growth factors often are effective. They can help speed up new blood cell production, reducing a person's need for transfusions and reducing infection risks.

Infection prevention

People with severe aplastic anemia are at risk for life-threatening infections. Even a common infection like a cold could become serious. To help prevent infection, people with severe aplastic anemia need to protect themselves from germs. Steps to take may include avoiding crowds and sick people. If you have severe aplastic anemia, talk with your doctor about how you can reduce your risk of infection.

If a fever or other signs of infection appear, the infection must be treated quickly. The most common treatment for infection is antibiotics.

Immunosuppressive therapy

Immunosuppressive therapy is one of two standard treatments that have the potential to offer a person with severe aplastic anemia a longer life. The other treatment, a transplant, is often recommended as the first treatment for children and young adults with a suitable sibling donor. Immunosuppressive therapy is often recommended as the first treatment for patients who:

Are older than age 40, though recommendations based on age vary among doctors and with other patient factors.
Are unable to tolerate a transplant because of other health problems or older age.
Do not have a suitable donor or cord blood unit for transplant.
Will be treated with transplant, but are waiting for a suitable donor to be found.
Choose immunosuppressive therapy after weighing the potential risks and benefits of all options.

The immune system is made up of organs and cells that work together to protect the body from infection and disease. The immune system uses white blood cells to fight infections. The white blood cells mark and attack cells that they do not recognize as belonging in the body. Immunosuppressive therapy uses drugs that suppress (weaken) the immune system. This treatment is based on the widely accepted theory that aplastic anemia is a result of the immune system attacking the bone marrow. Immunosuppressive therapy weakens the immune system's response and allows the marrow to make more blood cells. For many people, immunosuppressive therapy raises blood counts to normal or near normal levels and leads to long-term survival.

Immunosuppressive therapy has few short-term risks. However, people often must repeat or continue therapy for the long term. The therapy also increases the risks of getting a second disease such as myelodysplastic syndrome (MDS) or leukemia later on. To learn more about immunosuppressive therapy drugs and treatment results, see Immunosuppressive Therapy for Aplastic Anemia.

Bone marrow or cord blood transplant (BMT)

For many patients with severe or very severe aplastic anemia, a marrow or cord blood transplant is the preferred standard treatment. A transplant replaces the abnormal cells in the bone marrow with healthy blood-forming cells from a family member or unrelated donor or cord blood unit.

The donor for a transplant must closely match the patient's tissue type. The best donor is usually a matched sibling. For patients who do not have a suitable donor in their family, doctors may search the National Marrow Donor Program (NMDP) Registry for a matching adult volunteer donor or cord blood unit.

A transplant can offer the best chance for a cure of aplastic anemia, but it is not an option for all patients. A transplant may be a good option for patients who have a suitable donor or cord blood unit and are healthy enough to tolerate a transplant. Children and young adults tend to do better than older patients, but advances in transplant have enabled more older patients to undergo a transplant successfully.

Transplants for aplastic anemia can have serious risks. However, doctors have developed treatment methods to address many of these risks and transplant outcomes have improved in the last decade.

One risk that is greater for patients with aplastic anemia than for many other diseases is graft rejection or graft failure (when the transplanted cells do not grow and make blood cells for the body). Having many transfusions increases the risk of graft rejection because the patient's immune system may develop antibodies that can react against the transplanted cells. Today, doctors give aplastic anemia patients as few transfusions as possible. The transfused blood is also commonly treated with radiation and filtered to remove the white blood cells. These practices have improved transplant outcomes.

Another serious risk of transplant for patients with aplastic anemia is graft-versus-host disease (GVHD). This is a common transplant complication that can range from mild to severe. For patients who receive a transplant to treat leukemia or another cancer, GVHD may be associated with a beneficial graft-versus-leukemia effect. However, there is no benefit to GVHD for patients with aplastic anemia. Advances in the treatment of GVHD have reduced this risk, but doctors continue to search for better treatments.

If transplant is an option for you, your doctor can talk with you about the possible risks and benefits of a transplant. For statistics showing patients' results after transplant, see Severe Aplastic Anemia Transplant Outcomes.

Making treatment choices

If you or your child has severe aplastic anemia, it is important to see a doctor who is an expert in the disease. If your doctor has not treated other patients with aplastic anemia, ask him or her to refer you to an expert for consultation.

A doctor who is an expert in aplastic anemia can talk with you about your treatment options and explain the possible risks and benefits. Whatever treatment you and your doctor decide on, you may choose to be part of a clinical trial. Clinical trials help doctors gain knowledge that can improve treatments for patients in the future. Even standard treatments continue to be studied in clinical trials.

The two standard treatments, immunosuppressive therapy and transplant, have similar long-term survival rates for some groups of patients. Both treatments have potential risks and side effects:

A transplant has higher risks of life-threatening side effects early after treatment, but a transplant can bring a long-term cure.
Immunosuppressive therapy has fewer early risks, but most people are not cured and need treatment for the long term.
Both treatments have some risks of long-term side effects or complications.
The possible risks and benefits of these treatments vary from one person to another, depending on age and other health factors.

Many doctors recommend a transplant for patients age 20 or younger, especially those who have a suitably matched sibling donor. Doctors also recommend a transplant for many patients between age 20 and 40 who have a suitable sibling donor. For patients older than age 40 and those who do not have a suitable sibling donor, many doctors recommend trying immunosuppressive therapy first. However, age is only one of the factors to look at when making treatment choices. If a patient does not respond to immunosuppressive therapy within three to four months, a transplant using either a sibling or an unrelated donor or cord blood unit may be an option.

The time between diagnosis and transplant can affect transplant outcomes. To improve your chances of a successful transplant, you and your doctor can plan ahead. A consultation with a transplant doctor can help determine whether a transplant is a good option for you, either as the first treatment of choice or as a second treatment if immunosuppressive therapy fails.

Even if you begin treatment with immunosuppressive therapy, your doctor can take steps to be prepared if immunosuppressive therapy does not give you good results. Your doctor can check whether you have any possible donors in your family. He or she can also search the National Marrow Donor Program Registry for potential unrelated volunteer donors or cord blood units. That way, if you and your doctor decide you need a transplant later, the first steps of the donor search will be done and you may be able to move to transplant more quickly.

Information to share with your doctor

The Physician Resources section of this Web site includes information for doctors about planning for transplantation. You may want to share some of this information with your doctor.

More information on aplastic anemia

You can get further information about aplastic anemia from disease-specific organizations, such as the Aplastic Anemia & MDS International Foundation — request an information packet at https://www.toad.net/~aafa/aplastic/disease_information/educational
_material/index.php

For other organizations that offer information and resources, see Organizations that Can Help: A Searchable Directory.

Contributing editors

C. F. LeMaistre, M.D., Southwest Texas Methodist Hospital, San Antonio, Texas
Anthony S. Stein, M.D., City of Hope National Medical Center, Duarte, Calif.