Resources & FAQ

If you have been diagnosed with AL amyloidosis, there are two kinds of “L” (light chains) that you should know.  The light chains are represented by two Greek letters:  kappa (κ) and lambda (λ).  So, a patient with AL amyloidosis may have a disease emphasis with either the kappa or lambda type of light chain.  Lambda (λ) is more common than kappa (κ).  However, at this time, the type of light chain identified with a patient’s AL amyloidosis does not change the diagnosis or treatment.

AL may occasionally be associated with myeloma, because like AL amyloidosis, multiple myeloma affects the plasma cells inside the bone marrow. 

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In myeloma, there are so many plasma cells, that it clearly is a bone marrow cancer. It does not always form lesions, lumps or tumors, but the myeloma cells break down and expand inside the bone marrow, which can cause bone pain and fractures. This is not the case for AL amyloidosis. Although AL is a related disease, it is not clearly classified as a bone marrow cancer like myeloma or leukemia. There are myeloma and lymphoma patients who do develop AL amyloidosis.

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Approximately 15% of those diagnosed with multiple myeloma will also acquire AL amyloidosis. Even if a patient has myeloma associated with their amyloidosis, the treatments for AL amyloidosis are similar to those for myeloma.

When these light chain proteins assemble incorrectly, they are called abnormal, or misfolded, protein.  When they travel in the body, they become rigid and insoluble (unable to dissolve), and are made up of tiny fibers (fibrils).  This causes these misfolded proteins to gang up and cluster together, leaving deposits in and around body organs, connective tissues, muscles, and nerves.  This interrupts the body’s normal function and causes symptoms.  If this cluster of deposits is not slowed or stopped, then organ failure is possible.

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The pattern of where the amyloid deposits in the body are often different when comparing one patient to another because every person is unique.  Any number of organs and/or parts of the body can be affected, with the severity of damage varying from organ to organ as well as person-to-person.

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In AL amyloidosis, common combinations of organ involvement include: heart/kidney; heart/GI tract; and, kidney/peripheral nerves — but almost any combination is possible.  It is important to note that AL amyloidosis does not affect the brain.

Some symptoms can represent much milder ailments, even something like the flu, for example, gastric distress or diarrhea.  This is why you and your internist or family doctor must be alert for continuing, or increasing, symptoms. If your symptoms don’t stop, then keep asking questions of your medical team so they can give you an accurate diagnosis. 

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Blood and/or urine tests can indicate signs of the amyloid protein, but only bone marrow tests or other small biopsy samples of tissue or organs can positively confirm the diagnosis of amyloidosis. 

Getting a quick and timely diagnosis is vital.  For example, the kidney is involved in approximately 65% of AL amyloidosis cases, so if a high concentration of protein is seen in your urine on a lab test, it is a signal to dig deeper when looking for a diagnosis. 

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Some tests can be used for diagnosis as well as for monitoring a patient’s response to treatment, although organ responses are typically much slower than hematologic (blood) responses.  

These tests include:

A 24-hour urine collection to look at the level of protein in your urine sample.  Excess protein in the urine may be an indication of kidney involvement.  Urine immunofixation is a lab test to look for clonal immunoglobulin proteins in urine.  You may hear the term “Bence Jones proteins.”  These are free immunoglobulin light chains that are found in high levels in the urine.

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1. Testing for the level of ALP (an enzyme called “alkaline phosphatase”) should be included in your regular blood lab workup.  An ALP test measures the amount of this enzyme in the blood.  ALP is made mostly in the liver, but is also produced in bone and other parts of the body and can signal liver or bone problems.  Certain conditions cause large amounts of ALP in the blood, so if your ALP level is high, it follows that more tests should be done to find the cause.

2. Tests for abnormal antibody (immunoglobulin) proteins in the blood include the Freelite® (Serum Free Light Chain) Assay Test (also known as FLC test). A blood lab measurement of the light chains can be very helpful in initial diagnostic testing and continuous monitoring of the disease. This blood test is relatively inexpensive and it measures both the kappa (κ) and lambda (λ) light chain production as well as the ratio between them.

3. If heart involvement is suspected, then blood tests for heart biomarkers can aid in determining if a patient has signs of heart tissue strain or damage in their blood.  The results of these tests can be used as “markers” (or “biomarkers”) to first determine the extent of any damage, and then can be used regularly to monitor any future problems.  Two troponin tests can be done — cardiac serum troponin T and serum troponin I. The other important biomarker is N-terminal pro-brain natriuretic peptide (NT-proBNP) or brain natriuretic peptide (BNP).

4. Different laboratories use one versus another. Cardiac troponins T (cTnT) and I (cTnI) are released when the heart muscle has had some injury. In general, the more damage there is to the heart, the greater the amount of troponin T and I there will be in the blood. NT-proBNP is another “biomarker” that should be performed, especially if a person has symptoms such as swelling in the legs (edema), difficulty breathing, shortness of breath, and fatigue.  It is used to detect heart stress or strain. This blood test can be useful in distinguishing fluid in the lungs due to congestive heart failure (in which it would be elevated) or from lung or pleural disease (in which case it should be normal or near normal). The pleurae are the linings of the lung, and can be involved with amyloid. These biomarker blood tests can be affected by changes in kidney function, drugs, and other causes. They should be interpreted in the context of other tests of cardiac function, such as an echocardiogram or cardiac magnetic resonance imaging.

5. Another lab test for abnormal immunoglobulin proteins can be done with blood and/or urine.  It is called “immunofixation electrophoresis.”  This test helps to identify if one certain immunoglobulin is being over produced. Electrophoresis is a lab test where an electric current is applied to a substance (in this case, blood or urine) to separate it into its component parts.  With immunofixation electrophoresis, it is the immunoglobulins that are being separated, then they are stained for further diagnostic results. 

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The above blood or urine test results can be informative clues if they show something that is not within normal range.  They are the beginning phase of diagnosing AL (light chain) amyloidosis, but do not provide 100% accuracy for diagnosing a light chain abnormality.  More tests will be necessary if any type of amyloidosis is suspected.

Nonsurgical biopsies are also called minimally invasive biopsies.  They can be performed individually or in combination.  These can be done by taking small samples of the fat pad in the stomach, the inner lip area, the skin or inside the bone marrow.

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1. With a “fat pad biopsy,” your doctor will clean your skin around your stomach and, with a needle, take a small piece of the ‘fat pad’ under the skin.  What is taken from the needle is sent to a lab for analysis. Approximately 80% of the time you will get a clear diagnosis with a fat pad biopsy, however, this is still not at 100%. If it comes up negative, the doctor will want to continue with other diagnostic procedures to be certain of the diagnosis. 

2. Another biopsy site is the ‘labial salivary gland’ where a small tissue sample is taken from an area in the inner lip.

3. Testing of the skin involves a biopsy that is sent to a lab for analysis.

4. A bone marrow biopsy takes a small amount of bone as well as the marrow (cells and fluid) from inside the bone. These samples can help to determine the percentage of plasma cells, and when tested in the lab they can aid in identifying whether the abnormal plasma cells are producing kappa or lambda light chains.

Interestingly, if you get a negative result from a fat pad biopsy, the doctor may want to consider performing an additional labial salivary gland biopsy. This is because it was noted in a medical article that 60% of the people who got an additional labial salivary gland biopsy (after they tested negative with the fat pad biopsy) came up positive for amyloid.  So, if these two tests are performed back-to-back, the range of accuracy rises to about 91%.  That means that the more invasive surgery and biopsy of an inner organ can be reduced to approximately 9% of patients.

A small sample of an organ that is showing symptoms should be biopsied if amyloidosis is still suspected.  This is often done after biopsies of the fat pad, lip, skin, or bone marrow (as mentioned above) turn up negative.

For example, if both fat pad and labial salivary gland biopsies are negative, but there is a high level of protein found in the patient’s urine sample, then a biopsy of a kidney is the next step.

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In all biopsy cases, both nonsurgical and surgical, the lab analysis is the same. If an amyloid fibril has been deposited into body tissue, it can be discovered in a biopsy when the biopsy is chemically tested and viewed through a microscope with polarized light.  A stain called the “Congo-red stain” is put on the biopsy tissue and if the examiner then sees the light wave change to an apple-green color (called “birefringence”) then amyloid is confirmed.

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If any biopsy specimen results in a positive diagnosis for amyloidosis, then an accurate typing of the kind of amyloid protein is the next important step.

The echocardiogram (also called “echo”) is an ultrasound of the heart.  A doctor can look at the size and shape of the heart, and whether it is relaxing normally in between heartbeats. Amyloid cannot be seen directly, but it does make the heart larger and stiffer than normal.

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Other imaging tests for the heart have also shown to be useful.  One test is the MRI (magnetic resonance imaging), and, in this instance, is also referred to as CMR (for cardiac magnetic resonance).  CMR with a contrast agent called “gadolinium,” given by vein at the time of the scan, is a way to detect amyloid deposits in the heart.

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Pyrophosphate scanning, a nuclear medicine test, is also used to evaluate whether an unusual type of abnormality of heart muscle function (“cardiomyopathy”) is present. An intravenous injection of pyrophosphate is made while the patient is at rest, followed about an hour later by a set of images that are taken while the patient lies down under a camera. The images take about 15 minutes. These images are recorded on a computer for analysis, and recent data suggests this scan may be useful in distinguishing different types of amyloid heart disease.