What is Amyloidosis?

Amyloidosis is a group of rare diseases in which amyloid proteins build up in the body’s organs. Most often, when we speak of amyloidosis we are referring to a specific type known as light chain amyloidosis, also known as “AL amyloidosis”. Light chain amyloidosis is the focus of this review. For information on other types of amyloidosis go to Amyloidosis Foundation or Amyloidosis Support.

Amyloid is an abnormal protein made by cells, known as B cells or plasma cells, in the bone marrow that can deposit in any of the body’s tissues or organs and cause damage to those organs. The disease frequently affects the heart, kidneys, liver, spleen, nervous system and gastrointestinal tract. Amyloidosis affects fewer than 3,000 people in the United States annually. The Colorado Blood Cancer Institute (CBCI) is a referral center for patients with amyloidosis.

What causes Amyloidosis?

Although amyloidosis is not cancer, it is very serious and can be disabling or life threatening.  The exact cause of amyloidosis is not known.

Light chain amyloidosis occurs by itself, or in association with blood and bone marrow cancers such as multiple myeloma or lymphoma. The common problem is that, by chance, immune cells known as “B cells” begin to propagate and create exact copies of themselves, called “clones”. These B cell clones do what normal B cells do, that is produce immune proteins known as immunoglobulins. Immunoglobulins have two major components: a heavy chain and a light chain. Heavy chains have names such as IgG, IgA, or IgM. The light chains are either kappa or lambda type; most patients are the lambda type. For reasons which are not clear, in amyloidosis, the light chains are the problem. The body does not process and handle the light chains normally and they first build up in the blood, and then turn into long sticky proteins: amyloid. The amyloid then goes and infiltrates various organs of the body (heart, kidney, nerve, skin, intestines and so forth), damaging those organs. This process usually occurs over years.

There is also a familial or inherited form of amyloid, which has a different cause. Hereditary amyloidosis is a rare type and usually affects the liver, heart or nervous system, resulting into a gradual, progressive degeneration of the nerves. Thus, it is treated differently than the light chain type.

How is Amyloidosis diagnosed?

Amyloidosis is extremely challenging to diagnose, often resulting in a long period of time, sometimes measured in years, between the initial onset of symptoms and the proper diagnosis.

Given the fact that amyloidosis can affect so many different organs, a patient may see several different types of physicians (family practice, internal medicine, neurology are examples) in an effort to have their problem diagnosed. The physician must suspect amyloid and consider it as a cause of a patient’s symptoms in order to make a diagnosis. It is never blatantly obvious with routine blood tests or on physical examination. Consideration of the diagnosis of amyloidosis usually begins when a patient goes to the doctor complaining of symptoms resulting from amyloid damaging a particular organ. For example, If the kidney is involved, large amounts of protein normally leak out into the urine (proteinuria), resulting in swelling of the ankles and legs, or poor kidney function. Liver amyloidosis may result in enlargement of the liver, fluids collecting in the abdomen (ascites), or abnormal liver blood tests. Cardiac or heart amyloidosis usually results in difficulty breathing, passing out, or fluid retention. Sometimes patients bruise too easily, get nerve irritation (such as numbness or tingling of the arms or legs), or something called carpal tunnel syndrome. If amyloid is in the intestines, usually there is trouble with the appetite and the bowels, and there may be internal bleeding.

Amyloidosis often has no symptoms in its early stages. Only after the disease begins to interfere with organ function are systems usually detected. Signs of the disease are often varied, making it difficult to diagnose.

Once a physician, or patient, suspects that amyloidosis may be the cause, specialized blood and urine tests are completed. Eventually, a biopsy of an involved or affected organ is mandatory in order to see the amyloid proteins in the organ, using a special stain called a Congo Red stain. The nature of amyloidosis is that it often affects several parts of the body and as long as some tissue can be biopsied and examined for amyloid, one can make the proper diagnosis.

The most helpful blood tests are a comprehensive chemistry profile, including liver and kidney testing. A 24 hour urine collection should be done to measure the protein loss. One must do specialized blood tests, including the serum free light chain assay and a test called electrophoresis and immunofixation, to find the light chains in the blood. Further testing to check the heart (blood tests and an echocardiogram), nerves (nerve conduction studies), and intestines (endoscopy with biopsy) is often needed. It is important to remember that patients with amyloidosis can bleed abnormally and tests to check for this (PT, PTT, Factor X level), should be monitored prior to any biopsy. A bone marrow biopsy is done to look for other blood cancers and check for the abnormal B cell clones, as well as to do the special stain for amyloid (Congo Red). Often, a sample of the fat just under the skin and below the belly button is taken and stained for amyloid (fat pad aspirate).

It is very important when undertaking the diagnosis of amyloidosis to check for other blood cancers and to be sure that is the light chain type. This is called “amyloid tissue typing”, and is recommended.

What are the treatment options?

There is no cure for amyloidosis, but treatment may help manage the symptoms and limit further production of amyloid protein.

If the amyloidosis is associated with a blood cancer such as multiple myeloma or non-Hodgkin's lymphoma, then the treatment is that for the blood cancer. Usually, if that treatment is successful the amyloid will improve as well.

“Symptomatic” treatments are often very important (diet, activity, medications which can alleviate problems associated with certain organ damage) and should be discussed with the patient’s physician.

Normally, light chain amyloidosis is treated similar to the blood cancer multiple myeloma. Both are problems associated with B cell clones and light chain production.

Unfortunately, there is not yet a treatment which removes the amyloid deposited in the affected organ. Such a treatment is the focus of intensive research. One such medicine under investigation is NEOD001 - presently being studied at CBCI.

Treatment is directed toward decreasing the number of abnormal B cell clones, thereby decreasing the circulating light chains and stopping or greatly deceasing the production of new amyloid protein. This is called a “hematologic” or “blood” response. In such a situation, the body may be able to eliminate some of the amyloid protein from the affected organ and, as long as new amyloid protein is not being produced, result in improvement of the organ. This is called an “organ response” and is often, but not always, the result of amyloidosis treatment. An “organ response”, or improvement in the functioning of the organ, is what makes people with amyloidosis actually feel better when they receive treatment.

An “organ response” cannot generally occur without a “hematologic response”.

Therefore, when amyloidosis is treated, it is important to monitor the abnormal light chains in the blood and make sure they are decreasing; otherwise it would be very unusual to have an organ response.

The treatment of light chain amyloidosis is rapidly changing. Examples of treatments include using chemotherapy drugs and high-dose chemotherapy and autologous (using one’s one stem cells to support receiving a very high-dose of chemotherapy) transplant. Drugs commonly used to treat amyloidosis include: melphalan, cyclophosphamide, bortezomib, prednisone, dexamethasone, thalidomide and lenalidomide. Clinical trials are underway around the world trying to improve the treatment of this disease.

The physicians at the CBCI are the region’s experts in this disease and can provide second opinions or primarily treat an amyloidosis patient. The CBCI conducts clinical trials for amyloidosis. Furthermore, when high-dose chemotherapy and autologous stem cell transplant is done for amyloidosis patients, it is very important to receive that treatment at an experienced center. The transplant team at the CBCI is the largest and most experienced in the Rocky Mountain region and is devoted to treating this challenging disease.