How Is Fanconi Anemia Treated?

Doctors decide how to treat Fanconi anemia (FA) based on a patient’s age and how well (or how poorly) the patient’s bone marrow is producing new blood cells.

Goals of Treatment

Long-term treatments for FA can:

• Cure the anemia. Damaged bone marrow cells are replaced with healthy ones that can make enough of all three types of blood cells on their own.
• –OR–
• Treat the symptoms without curing the cause. This is done using medicines and other substances that can help your body make more blood cells for a limited time.

Observation and Short-Term Treatment

If you or your child has FA, but your bone marrow is still able to make many of the new blood cells your body needs, your doctor may perform frequent blood count checks. During this period of observation, your doctor will probably want you to have bone marrow exams once a year. Your doctor also will screen you closely for any signs of cancer or tumors.

If your blood counts begin to drop sharply and stay low, your doctor may assume your bone marrow is failing. He or she may give you antibiotics to help your body fight infections.

In the short term, your doctor also may want to give you blood transfusions to increase your blood cell counts to normal levels. However, long-term use of blood transfusions can reduce the chances that other treatments, which can help your body make enough blood cells on its own, will work.

Long-Term Treatment

There are four main types of long-term treatment for FA:

• Bone marrow transplant
• Androgen therapy
• Synthetic growth factors
• Gene therapy

Bone Marrow Transplant

Bone marrow transplant, also called stem cell transplant, is the current standard treatment for patients with FA that's causing major bone marrow failure. Healthy bone marrow cells from another person, called a donor, are used to replace the abnormal cells in your bone marrow.

Bone marrow transplant is most successful in younger people who have few or no serious health problems, a brother or sister donor, and few or no previous blood transfusions.

Successful bone marrow transplants will allow your body to make enough of all three types of blood cells to work normally. However, if you've had a transplant to treat FA, you will still be at risk for some types of blood cancer and for developing cancerous solid tumors. Your doctor will check your health regularly and often after the procedure.

Finding a donor. A key factor for bone marrow transplant success is finding a donor whose bone marrow cells your body won't reject. Your body is more likely to accept cells that can work with your own cells without causing unhealthy side effects. If the new cells don't match, your body's immune system may attack and destroy them. This is similar to how the body responds when it's invaded by something from the outside, like a virus or bacteria.

To determine whether a donor's cells will work with yours, your doctor will use a blood test called HLA typing. This test looks at proteins on the surface of blood cells. The proteins are called human leukocyte antigens (HLA). Your blood and the donor's blood are tested, and the HLA antigens on the blood cells are compared. If your HLA is similar to the donor's, it means your body is less likely to try to fight and destroy the donor's cells.

The greatest chance (up to 80 percent) for a successful bone marrow transplant generally is if your brother or sister donates bone marrow and if you and your sibling have matching HLA.

It's possible to have a successful bone marrow transplant from a donor who isn't related to you, but success rates for this type of transplant are less than 50 percent. It's also possible to have a successful transplant using cells from umbilical cord blood. Because these types of transplants are riskier, doctors only use cells from nonrelated donors for transplants:

• If you have cancer (leukemia or myelodysplastic syndrome)
• If you have no HLA-matched brother or sister to donate cells
• If your body can't tolerate other treatments for bone marrow failure

Receiving the transplant. Bone marrow transplants are done in special units in hospitals to try to protect the person receiving the transplant from infections. Before the transplant, you receive high doses of chemotherapy, radiation therapy, or both. These treatments destroy the abnormal bone marrow that isn't producing blood cells.

A sample of bone marrow is taken from the donor and given to you through a vein. The donated bone marrow cells travel to your bone marrow and start to make healthy blood cells. If the transplant is successful, the new bone marrow cells multiply and begin making new, healthy blood cells within 3 to 4 weeks.

Possible complications. After a bone marrow transplant, you may be in the hospital for weeks or months. During this time, you're isolated and closely watched for infections and other complications. Complications are most likely to occur in the first 100 days after a transplant.

Complications after bone marrow transplant include:

• Rejection of the new cells
• A condition called graft rejection
• A condition called graft-versus-host disease (GVHD)

Graft rejection occurs when your immune system destroys the new bone marrow cells. This occurs in 5 to 10 percent of people who get bone marrow transplants. It's more likely to happen in people who have had several transplants.

GVHD happens when the new white blood cells, created by the donated bone marrow cells, attack your body. Signs and symptoms include skin inflammation, severe diarrhea, and liver disease. GVHD can occur soon after transplant, or it can develop slowly and can last for months or years. GVHD most often happens in older people and those who receive unmatched transplants.

To help prevent GVHD, the donor marrow is sometimes treated, or you may get medicines that suppress the immune system after the transplant. Sometimes symptoms of GVHD are treated with medicines such as steroids.

Androgen Therapy

Before improvements made bone marrow transplants more effective, androgen therapy was the standard treatment for people with FA. Androgens are artificial male hormones that can help your body make more blood cells for long periods.

Androgens are effective in increasing your red blood cell count. They also help to increase your platelet count. They're less effective in making more white blood cells in your body.

Unlike bone marrow transplant, androgens don't enable your bone marrow to produce enough of all three types of blood cells on its own. You may need ongoing treatment with androgens to control the effects of FA. Also, androgens eventually lose their ability to help your body make more blood cells, which means you will need other treatments.

Androgen treatment can have serious side effects, such as liver disease, and it can't prevent you from developing leukemia.

Synthetic Growth Factors

Your doctor may choose to treat your FA with substances known as growth factors. These are substances found in your body, but they also can be man-made. They help your body make more red and white blood cells. Growth factors that can help your body make more platelets are still being researched. One of the more common growth factors used to treat FA is called EPO, or erythropoietin (e-RITH-ro-PO-e-tin). EPO has some risks. Based on your situtation, your doctor will decide whether EPO's benefits outweigh its risks.

More research is needed on growth factor treatment for FA. Early results suggest that growth factors may have fewer and less serious side effects than androgens.

Gene Therapy

Researchers are looking for ways to replace abnormal FA genes with normal, healthy genes. They believe that the replacement genes will be able to make the proteins needed to repair and protect your bone marrow cells.

Gene therapy uses viruses that have been altered so that they can deliver normal genes to replace abnormal ones in FA patients' bone marrow stem cells.

Early results hold promise, but this form of treatment for FA is still in the experimental stage.

Surgery

Surgery may be needed to improve the use of arms, thumbs, hips, legs, and other parts of the body that are malformed or underdeveloped due to birth defects caused by FA.

If your child is born with a heart defect linked to FA called ventricular septal defect, he or she may need surgery to close the hole in the heart's wall so the heart can function normally.

Children with FA also may need surgery to correct problems in the digestive system that can harm their nutrition, growth, and survival. One of the most common problems is an FA-related birth defect where the windpipe (trachea), which carries air to the lungs, is connected to the esophagus, which carries food to the stomach. This can cause serious breathing, swallowing, and eating problems and can lead to lung infections. Surgery is needed to separate the two organs to allow normal eating and breathing.