Amyloidosis

Amyloidosis is not cancer, but it is a serious, potentially life-threatening condition that can occur because of some cancers. The basis of amyloidosis is the amyloid, which is an abnormal protein that enters tissues or organs. When enough amyloid proteins are present in an organ to interfere with its functioning and cause symptoms, it becomes a condition called amyloidosis.

Only in the past few decades have doctors and researchers begun to understand the nature of amyloid proteins and how they can cause damage. Research is ongoing to learn more.

Types of amyloidosis

There are different types of amyloidosis, including the following:

AL amyloidosis. This is the most common type of amyloidosis in the United States. The amyloid proteins that accumulate in the tissues in this condition are known as light (L) chains. AL amyloidosis is not usually associated with another underlying condition, although it is sometimes associated with multiple myeloma.

AA amyloidosis. In this condition, the amyloid protein that accumulates in the tissues is known as the A protein. AA amyloidosis is associated with such chronic diseases as diabetes, tuberculosis, rheumatoid arthritis, or inflammatory bowel disease. It may also accompany aging. The spleen, liver, kidneys, adrenal glands, and lymph nodes may be involved.

Hereditary amyloidosis (ATTR). Hereditary amyloidosis is rare. It is a specific type of amyloidosis that can be passed down from generation to generation in a family. It may cause peripheral sensory and motor neuropathy problems (issues relating to the central nervous system), carpal tunnel syndrome, and eye abnormalities. The most common subtypes involve the transthyretin (TTR) protein.

This section covers AL, AA, and hereditary amyloidosis. Other types of amyloidosis include ß2 microglobulin amyloidosis, which occurs in some patients with chronic renal (kidney) problems, and localized forms of amyloidosis.

Symptoms and Signs

Symptoms of people with amyloidosis vary widely. People with amyloidosis may experience the symptoms or signs listed below. Sometimes, people with amyloidosis do not show any of these symptoms. Or, these symptoms may be caused by another medical condition. If you are concerned about a symptom or sign on this list, please talk with your doctor.

Symptoms of amyloidosis are often determined by the organ or system that is affected by the protein buildup. For example:

• Amyloidosis in the kidneys will hinder the kidneys' ability to filter wastes and break down proteins. Therefore, large amounts of protein may be present in the urine, or the kidneys may fail to function.
• In the liver, amyloidosis may cause the liver to greatly increase in size and function abnormally.
• Amyloidosis of the heart may cause arrhythmia (irregular heart beat), enlarge the heart, and cause poor heart function.
• Amyloidosis of the gastrointestinal tract may cause problems with the digestion and absorption of food nutrients, bleeding, obstructions, and thickened tongue (macroglossia), as well as problems with the esophagus, including gastrointestinal reflux disease (GERD).
• A goiter (a noncancerous enlargement of the thyroid gland) may result from amyloidosis of the thyroid gland.
• Problems breathing, including shortness of breath, may occur from amyloidosis in the lungs.
• Peripheral neuropathy, including numbness, weakness, and tingling of the arms or legs, may occur. Carpal tunnel syndrome may also occur.

Other general symptoms of amyloidosis include:

• Fatigue
• Unexplained weight loss
• Anemia (low level of red blood cells)
• Weak hand grip
• Skin changes
• Clay-colored stools
• Joint pain

Treatment

Often, the most effective treatment for amyloidosis is the treatment and control of the underlying disease, if there is one.

This section outlines treatments that are the standard of care (the best proven treatments available) for amyloidosis. When making treatment plan decisions, patients are also encouraged to consider clinical trials as an option. A clinical trial is a research study to test a new treatment to evaluate whether it is safe, effective, and possibly better than standard treatment. Your doctor can help you review all treatment options. For more information, see the Clinical Trialsand Current Research sections.

Treatment overview

Different types of doctors often work together to create a patient's overall treatment plan that combines different types of treatments. This is called a multidisciplinary team.

Descriptions of the most common treatment options for amyloidosis are listed below. Treatment options and recommendations depend on several factors, including the type of amyloidosis, the type of underlying disease, possible side effects, and the patient's preferences and overall health. Learn more about making treatment decisions.

Medication and chemotherapy

Medication may be used to control the problems associated with amyloidosis. Steroids, alone or in combination with other drugs, have been shown to be effective.

Chemotherapy is the use of drugs to kill abnormal cells, usually by stopping the cells' ability to grow and divide. It is most commonly used for the treatment of cancer. However, chemotherapy drugs are also useful in other conditions, including amyloidosis, when they are used to kill the abnormal plasma cells. Systemic chemotherapy is delivered through the bloodstream to reach cells throughout the body. Chemotherapy may be given by a medical oncologist (a doctor who specializes in giving chemotherapy to treat cancer), or a hematologist (a doctor who specializes in treating blood disorders). A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. A patient may receive one drug at a time or combinations of different drugs at the same time.

Some of the most common chemotherapy drugs used to treat amyloidosis are chlorambucil (Leukeran), melphalan (Alkeran), and cyclophosphamide (Cytoxan, Neosar). The side effects of chemotherapy depend on the individual and the dose used, but they can include nausea, vomiting, and fatigue. These are typically treatable when they do occur. In addition, low levels of red blood cells (anemia) can occur with melphalan and similar drugs. Late effects are uncommon with these types of treatments.

Newer drugs being evaluated for amyloidosis include lenolidamide (Revlimid) and bortezomib (Velcade). These drugs are currently being studied in clinical trials to determine their effectiveness in amyloidosis.

Learn more about chemotherapy and preparing for treatment. The medications used to treat diseases are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions by using searchable drug databases.

Immunotherapy

Immunotherapy (also called biologic therapy) is designed to boost the body's natural defenses. It uses materials made either by the body or in a laboratory to bolster, target, or restore immune system function. Alpha interferon is a form of biologic therapy given as injections under the skin. This is sometimes used to help relieve symptoms caused by the condition, but it can have significant side effects including fatigue, depression, and flu-like symptoms. Learn more about immunotherapy.

Surgery

Surgery used to treat amyloidosis may include organ transplantation. Liver transplantation has been effective in certain types of hereditary amyloidosis. Learn more about what to expect during surgery.

Dietary therapy

Dietary therapy may be used to decrease the production of amyloid proteins or to lessen the burden on affected organs. This means doctors will recommend a specific plan about what to eat and drink and what to avoid. For example, if amyloidosis affects the heart or kidneys, a low-sodium diet may be recommended. It is important to note that, even though amyloid is a protein, there is no link between amyloidosis and eating protein-rich foods.

Stem cell transplantation/bone marrow transplantation

A stem cell transplant is a medical procedure in which diseased bone marrow is replaced by highly specialized cells, called hematopoietic stem cells. Hematopoietic stem cells are found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because it is the blood stem cells that are typically being transplanted, not the actual bone marrow tissue.

In some cases, stem cell transplantation may be used to introduce healthy bone marrow cells that will not make amyloid proteins. The real impact of stem cell transplantation on amyloidosis is still being studied in clinical trials.

Before recommending transplantation, doctors will talk with the patient about the risks of this treatment and consider several other factors, such as the type of disease, results of any previous treatment, and patient's age and general health.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cells: autologous (AUTO) and allogeneic (ALLO).

In an AUTO transplant, the patient's own stem cells are used. The stem cells are obtained from the patient when he or she is in remission from previous treatment. The stem cells are then frozen until they are needed, usually after the high-dose treatment (explained below) is completed.

In an ALLO transplant, stem cells are obtained from a donor whose tissue matches the patient's on a genetic level; this testing is called HLA-typing. Most often, a patient's brother or sister serves as the donor, although unrelated donors can serve as the donor too. Millions of people worldwide have volunteered to donate stem cells for patients who do not have matched family members; your health care team will search a computer registry to look for a match. In addition, a donation of stem cells derived from umbilical cord blood is sometimes considered if family donors are not available.

In both types, the goal of transplantation is to destroy abnormal plasma cells and allow replacement blood stem cells to create healthy bone marrow. In most stem cell transplants, the patient is treated with high doses of chemotherapy and/or radiation therapy to destroy the abnormal cells which are making the amyloid protein. This also destroys the patient's bone marrow tissue and suppresses the patient's immune system so that, in an ALLO transplant, the donor cells are not rejected by the body. After the high-dose treatment is given, blood stem cells are infused into the patient's vein to replace the bone marrow and restore normal blood counts from donor cells. Sometimes, ALLO transplants can also be performed after giving lower doses of chemotherapy and/or radiation therapy that are still sufficient to suppress the immune system and allow growth of the donor cells. (These transplants, sometimes termed “mini-transplants” or reduced-intensity transplants, have less immediate side effects, allowing the procedure to be used for older patients.)

For both AUTO and ALLO transplant types, the replacement cells engraft (begin to make new blood cells) and turn into healthy, blood-producing tissue in 10 days to three weeks. Destroying the patient's own marrow reduces the body's natural defenses, temporarily leaving the patient at an increased risk of infection. Until the patient's immune system is back to normal, patients may need antibiotics and blood transfusions, and they need to follow certain safety restrictions provided by the health care team to help avoid infections.

In an ALLO transplant, another major risk is that the donor's cells will recognize the patient's body as foreign, causing graft-versus-host disease (GVHD). GVHD may be a serious complication of allogeneic transplants and can be fatal. Other side effects may include liver problems, diarrhea, infections, and rashes. However, GVHD can also be a benefit because the donor cells can recognize the abnormal cells as foreign and destroy these cells, a mechanism that is one of the major reasons why ALLO transplantation generally works so well over the long term. The risk of GVHD can be reduced with exact HLA-type matching and the use of preventive drugs.

In an AUTO transplant, there is little risk of GVHD because the replacement stem cells are the patient's own cells. Learn more about bone marrow and stem cell transplantation.