AL amyloidosis

Amyloid light-chain (AL) amyloidosis is a rare and serious condition in which a substance called amyloid builds up in the body. The amyloid forms when certain proteins fold the wrong way and stick together. Those proteins are called light chains.

Other names for AL amyloidosis are:

• Immunoglobulin light chain amyloidosis.
• Primary amyloidosis.
• Systemic AL amyloidosis.

As amyloid builds up in the body, it can cause life-threatening organ damage. AL amyloidosis may affect the heart, kidneys, nervous system, liver, digestive tract and other parts of the body. If the condition affects the heart, it can lead to heart failure.

AL amyloidosis sometimes happens with a cancer of the bone marrow called multiple myeloma. However, most people with AL amyloidosis do not have multiple myeloma.

AL amyloidosis symptoms depend on the parts of the body affected. The symptoms may seem like those of common conditions. For example, you might feel very tired or be short of breath. Letting your care team know when you don't feel well may help find AL amyloidosis earlier. Newer medicines can slow the disease and are helping people live longer. Some people also may need a blood stem cell transplant, although that's now becoming less common.

There are different types of amyloidosis. The type of amyloidosis is based on the protein that forms the amyloid deposits. This article focuses on AL amyloidosis.

Other types of amyloidosis include:

• Amyloid transthyretin (ATTR) amyloidosis.
• Amyloid A amyloidosis, also called AA amyloidosis.
• Other, rarer types, including apolipoprotein A-I (AApoAI) and apolipoprotein A-II (AApoAII).

Amyloidosis also may be grouped by how much of the body it affects.

• If the condition affects more than one part of the body, it's called systemic amyloidosis.
• If the condition only affects one part of the body, it's called localized amyloidosis.

If amyloidosis affects the heart, it's called cardiac amyloidosis.

Symptoms of AL amyloidosis happen as amyloid builds up in the body. They vary depending on which organs are affected. The symptoms may look like those of other conditions.

AL amyloidosis symptoms often affect more than one part of the body. That means it's a systemic condition. Common symptoms may include:

• Feeling very tired, even after getting rest.
• Feeling weak or not able to do as much physical activity as usual.
• Shortness of breath or trouble breathing with activity or even at rest.
• Swelling in the legs, ankles or feet.
• Not feeling very hungry.
• Losing weight without trying.
• Numbness, tingling or burning in the hands or feet.

AL amyloidosis often affects the heart. If this happens, it's called cardiac AL amyloidosis. Symptoms can include:

• Chest pain, especially during activity.
• Low blood pressure.
• Fast, pounding or fluttering heartbeats.
• Feeling dizzy or fainting, especially after standing up.
• Swelling in the legs, ankles, feet or belly area, which can be a sign of heart failure.

If AL amyloidosis affects your kidneys, you may have foamy or frothy urine.

If the condition affects your digestive system, symptoms may include:

• Diarrhea, constipation or changes between the two.
• Nausea.
• Weight loss.
• Belly pain.
• Bleeding, such as blood in the stool, or black, tarry stools.
• Feeling full quickly during meals.
• Trouble swallowing.

Some people with AL amyloidosis also have:

• Easy bruising.
• Bruising or purple-colored skin around the eyes. Depending on skin color, this change may be easier or harder to see.
• Swollen tongue, called macroglossia.

Tell your healthcare team about all the symptoms you have. Your care team can do tests to find the cause of your symptoms. Your care team may test for amyloidosis if you have several of these symptoms together.

When to see a doctor

Make an appointment for a health checkup if you have symptoms of AL amyloidosis.

If you have AL amyloidosis, tell your care team about new symptoms or symptoms that get worse. Quick care matters because it may help limit further organ damage.

When to seek emergency care

AL amyloidosis can affect the heart. It can lead to serious heart symptoms.

Get medical help right away if you have:

• Chest pain.
• Sudden, severe shortness of breath.
• Very fast or irregular heartbeats with shortness of breath, chest pain or fainting.

In all types of amyloidosis, proteins fold the wrong way and stick together. This causes deposits called amyloid. But the amyloid can form from different starting proteins.

In AL amyloidosis, the starting proteins come from white blood cells called plasma cells. Plasma cells make antibodies that help the body fight infection. Antibodies contain two types of light chains, called kappa and lambda. Everyone typically has both kappa and lambda light chains. In AL amyloidosis, one group of plasma cells makes too much of one of these types of light chains.

The group of plasma cells that has changed and makes the light chains that fold the wrong way is called a clone. A condition in which one group of plasma cells works differently from the other plasma cells is called a plasma cell disorder. Another name for it is a clonal plasma cell disorder.

An example of a plasma cell disorder is monoclonal gammopathy of undetermined significance (MGUS). MGUS is a condition in which a small group of plasma cells makes a harmful protein but does not cause organ damage. Some people are diagnosed with MGUS before they get AL amyloidosis. Once AL amyloidosis develops, the condition is no longer considered MGUS.

Multiple myeloma also is a plasma cell disorder. It's a cancer of the bone marrow. Some people have both AL amyloidosis and multiple myeloma.

Less commonly, AL amyloidosis happens with other blood conditions. Examples are:

• Waldenstrom macroglobulinemia.
• Chronic lymphocytic leukemia.
• Lymphoma.

Growing older raises the risk of AL amyloidosis. The condition is more common in older adults, often those in their mid-60s.

Having a plasma cell disorder called monoclonal gammopathy of undetermined significance (MGUS) also may raise your risk. But most people with MGUS do not develop AL amyloidosis.

AL amyloidosis causes harmful proteins to build up in the body's organs and tissues. The complications depend on the part of the body affected.

Possible complications include:

• Heart failure. This condition is common with AL amyloidosis. The amyloid deposits make the heart thick and stiff. That makes it harder for the heart to stretch and fill with blood. When this happens, it's called restrictive cardiomyopathy. The heart can't pump enough blood to meet the body's needs. Without treatment, heart failure can be life-threatening.
• Irregular heartbeats, called arrhythmias. Damage from AL amyloidosis can affect the electrical signals that tell the heart to beat. The heart may beat too fast or too slow. Or the heartbeat may not follow a steady pattern. Some irregular heartbeats can lead to fainting, stroke or, rarely, sudden cardiac arrest.
• Kidney damage. AL amyloidosis can cause the body to pass too much protein in the urine. This is called nephrotic syndrome. The syndrome can cause the kidneys to stop working as they should over time. A severe loss in the kidneys' ability to work is called end-stage kidney disease. A lot of protein loss from the kidneys also raises the risk of blood clots.
• Nerve damage. Amyloid can damage nerves that control feeling and movement. This can lead to numbness, pain or weakness. Damage also can affect the part of the nervous system that controls digestion, sexual function and blood pressure.
• Liver or digestive system damage. Amyloid can make the liver swell and affect how it works. The changes may make it harder for the body to absorb nutrients. Changes in the digestive tract may cause symptoms such as nausea, diarrhea, constipation, weight loss or bleeding.
• Bleeding. AL amyloidosis can cause low levels of a protein that helps blood clot. That protein is called factor X. If blood doesn't clot, you may be at risk of easy bruising and serious bleeding.

Regular health checkups can help your care team watch for these complications.

AL amyloidosis can be hard to diagnose. Its early symptoms can be a lot like those of more-common conditions.

To diagnose AL amyloidosis, a healthcare professional examines you. You usually are asked about your symptoms. You also may be asked about your health history and your family's health history. But unlike other types of amyloidosis, AL amyloidosis does not run in families.

Your healthcare professional orders tests to look for causes of your symptoms.

Blood and urine tests

Some blood and urine tests can help find signs of AL amyloidosis. Results from some of the tests help your healthcare team learn how much organ damage you have. But no single blood or urine test alone can confirm a diagnosis of AL amyloidosis.

Blood and urine tests may include:

• N-terminal pro-B-type natriuretic peptide (NT-proBNP). The heart releases this substance into the bloodstream when it's under increased strain or pressure. High levels may be a sign that AL amyloidosis has affected the heart. Changes in the NT-proBNP level also help show how amyloidosis treatment is working. If NT-proBNP testing is not available, you may have a regular BNP test.
• Troponin T or troponin I. Troponin is a protein found in heart muscle. Higher levels of the protein may mean you have heart damage. Your troponin level helps your healthcare team know how much AL amyloidosis affects your heart.
• Estimated glomerular filtration rate (eGFR). This test shows how well the kidneys are working. It checks the level of a waste product made by muscles, called creatinine, along with other information. In amyloidosis, eGFR may go down if the kidneys are not working well.
• Urine protein study. This test checks how much protein leaves the body through urine. A high level may be a sign of kidney damage caused by amyloid deposits.
• Immunoglobulin free light chains. This blood test measures both kappa and lambda free light chains and compares their levels. The difference between them is called the difference in free light chains (dFLC). This result can help show how active AL amyloidosis is and how well treatment is working.
• Electrophoresis and immunofixation. These tests check blood and urine for a protein called a monoclonal protein (M protein). Finding an M protein can suggest a plasma cell disorder. But more testing is needed to confirm the diagnosis.

Imaging tests

Imaging tests alone cannot diagnose AL amyloidosis. But you may have imaging tests if your healthcare team thinks the condition affects your heart. These tests may include:

• Echocardiogram. This is one of the first tests done to see whether AL amyloidosis affects the heart. Sound waves make pictures of the beating heart. The test shows the thickness of the heart walls and how well the heart squeezes and pumps blood. It also can show patterns in the heart that suggest amyloid buildup.
• Heart MRI, also called cardiac MRI. This test uses radio waves and a strong magnetic field to make clear pictures of the heart tissue. It shows the structure of the heart. It also can show patterns related to amyloid buildup. This test may be done if the images from an echocardiogram do not give enough information.

You may have other imaging tests depending on the part of your body affected by AL amyloidosis.

Biopsy

A biopsy is needed to confirm that a person has AL amyloidosis. During a biopsy, a healthcare professional removes a piece of body tissue. The sample is checked under a microscope.

Your healthcare team chooses the type of biopsy based on where the amyloid is most likely to be found in your body. Your care team talks with you about which test is right for you.

• Abdominal fat pad aspirate or biopsy. This procedure looks for amyloid in a small piece of fat from under the skin of your belly.
• Bone marrow aspiration and biopsy. This procedure removes samples of liquid and solid tissue from the bone marrow. The samples are checked for signs of plasma cells that make the light chains responsible for AL amyloidosis. A bone marrow biopsy also may show amyloid deposits.

Sometimes a biopsy does not find amyloid. If you had both types of biopsies and your healthcare team still thinks you may have AL amyloidosis, you might need a biopsy of areas such as the:

• Heart.
• Kidney.
• Liver.
• Digestive tract.
• Nerves.

Your care team uses the results of all your tests to diagnose AL amyloidosis and plan your care.

There's no cure for AL amyloidosis. Some damage caused by amyloid buildup may last even after treatment. But newer treatments can help slow or stop more amyloid from forming. This may help organs work better over time.

Your healthcare team works with you to create a treatment plan that fits your condition and symptoms. The goal of treatment is to quickly stop plasma cells from making harmful light chains. Other goals are to:

• Manage symptoms.
• Keep the condition from getting worse.
• Lower the risk of complications.

Treatment often starts with medicines. Medicines can help slow the disease and ease your symptoms. The types of medicines you need may change over time.

Medicines

If you have AL amyloidosis, you usually get medicines to stop certain blood cells from making harmful light chains. Lowering the amount of harmful light chains slows or stops new amyloid from forming.

These medicines are often given together for people newly diagnosed with AL amyloidosis:

• Daratumumab-hyaluronidase (Darzalex Faspro).
• Bortezomib (Velcade).
• Cyclophosphamide (Cytoxan).
• Dexamethasone.

The combination of these treatments may be called Dara-CyBorD or Dara-VCd.

Not everyone receives all four medicines. The medicines you receive depend on several things, including:

• The part of the body affected.
• How severe your condition is.
• Whether you have other health conditions.
• How well your care team expects you to tolerate treatment.

Your healthcare team may start with a few medicines and change the doses as needed. If the first treatment stops working or does not work well enough, your healthcare team may use other medicines.

Your healthcare professional also may give you medicines to treat your symptoms and to prevent complications. For example, you may get medicines to treat irregular heartbeats.

Some medicines commonly used for heart failure or high blood pressure may not work well for people with amyloidosis. They also may cause blood pressure to drop too low. Your healthcare team chooses and adjusts these medicines carefully.

Surgery or other procedures

Some carefully selected people with AL amyloidosis may need an autologous blood stem cell transplant.

Stem cells are very young cells that help make blood cells. Autologous means that the stem cells come from your own body. An autologous blood stem cell transplant can be physically demanding. Your healthcare team looks at your heart, kidneys, other organs and overall health before deciding whether it is right for you.

Before the transplant, you get medicines that help your body make more stem cells for your blood. A healthcare professional then places a needle into a vein in your arm and removes some blood. The blood goes through a machine that collects the stem cells. The collected stem cells are frozen and saved. The rest of the blood goes back into your body.

Next, you get high-dose chemotherapy medicines to kill many of the cells that make harmful light chains. This treatment also affects healthy cells in the bone marrow for a short time. To help your bone marrow recover, your stored stem cells are then returned to your body through a vein. The stem cells help your body make new blood cells.

Other treatments

Other treatments depend on the organs affected by amyloid.

Some people with AL amyloidosis that affects the heart or other parts of the body may need other treatments. For example, if the condition causes serious changes in your heartbeat, you may need a heart device such as a pacemaker.

If AL amyloidosis causes a lot of damage to your kidneys, you may need a treatment called dialysis.

Sometimes, AL amyloidosis causes heart or kidney failure that can't get better. If this happens, a heart transplant or kidney transplant may be needed.

Follow-up care

After treatment for AL amyloidosis, you need regular health checkups. These checkups may include tests to look at any affected organs. Test results can show your healthcare team how well treatment is working.

Care team

If you have AL amyloidosis, different healthcare professionals work together to treat your condition and support your care. You do not have to manage the condition on your own.

Your specific care team depends on your needs but may include:

• Doctors who specialize in blood diseases, called hematologists.
• Doctors trained in heart conditions, called cardiologists.
• Doctors trained in kidney conditions, called nephrologists.
• Doctors trained in nerve conditions, called neurologists.
• Doctors trained in digestive system conditions, called gastroenterologists.
• A primary care healthcare professional.

Prognosis means what may happen over time. It is an estimate of what will happen. But it doesn't say what exactly will happen It also means how well you may do after treatment. How well a person with AL amyloidosis does varies widely. It is different for each person.

AL amyloidosis is a serious condition that can be life-threatening, especially when there is a lot of heart damage. But newer treatments have improved the outlook for many people with AL amyloidosis. When treatment works well, it can stop the body from making harmful light chains. This can help prevent more organ damage and may help some organs work better.

AL amyloidosis often gets worse faster than other types of amyloidosis, such as wild-type ATTR amyloidosis.

In general, your prognosis for AL amyloidosis depends on:

• Which organs are affected and how much damage there is. How much the heart is affected has the greatest effect on prognosis. The more AL amyloidosis has damaged the heart, the less well a person may do over time. But how well the kidneys and other organs do also matter.
• The stage of the condition. In general, a higher stage means more-severe disease.
• How early you start treatment. Starting effective treatment before a lot of organ damage happens is linked to better outcomes.
• How well treatment works for you. In general, people tend to do better when treatment for AL amyloidosis quickly and effectively lowers the level of harmful light chains.

Your prognosis can change over time. After treatment begins, your healthcare team looks at changes in your light-chain levels. They also look at how your organs are working and your symptoms. This helps the team understand what your prognosis may be based on your own results.

AL amyloidosis can make everyday activities harder because you may feel tired, weak or short of breath. These steps may help you manage symptoms and stay as active as you can.

• Take your medicines as directed.
• Go to your regular health checkups.
• Do not smoke.
• Follow your healthcare team's advice about salt and fluids.
• Talk with your care team before making big changes to your diet or activities.
• Stay active in ways your healthcare team says are safe.
• Rest when you feel tired.

It also is important to manage emotional stress. Learning that you have AL amyloidosis may be hard. Some people find that talking about their concerns with others in similar situations can help. You might try to connect with friends or family or join a support group.

If you are worried about your risk of AL amyloidosis, make an appointment with your healthcare professional. You may be sent to a doctor trained in heart diseases or blood disorders. If AL amyloidosis is found early, treatment may work better.

Appointments can be brief. Because there's often a lot to talk about, it's a good idea to be prepared for your appointment. Here's some information to help you get ready.

What you can do

When you make your appointment, ask if you need to do anything ahead of time. For example, you may be told not to eat or drink for a while before some tests.

Other things you can do to prepare:

• Write down your symptoms. Include those that may not seem related to amyloidosis.
• Write down important personal information. Tell your healthcare team about any family history of amyloidosis. Knowing as much as you can about your family history can be helpful.
• Make a list of all the medicines, vitamins and supplements that you take. Include the doses.
• Ask someone to go with you to help you remember what your care team says.

Also write down questions to ask your healthcare team. For AL amyloidosis, some basic questions include:

• What organs are affected?
• What tests do I need?
• What treatments do I need?
• What types of side effects can I expect from treatment?
• What are the possible complications?
• How do I need to change my diet or activities?

Don't hesitate to ask other questions during your appointment.

What to expect from your doctor

Your healthcare team usually asks many questions, such as:

• When did your symptoms start?
• Do the symptoms come and go or do you have them all the time?
• Does anything make your symptoms better or worse?
• How is your appetite?
• Have you recently lost weight without trying?
• Have you had any swelling in your legs, feet or ankles?
• Have you felt short of breath?
• Are you able to work and do your usual daily tasks?
• Has anyone in your family ever been diagnosed with amyloidosis?

Staging is a way to describe how serious AL amyloidosis is. It also helps your healthcare team know your outlook, also called prognosis. But it doesn't tell you exactly what will happen. Staging helps your healthcare team plan the right treatment for you.

There are several staging systems available to tell how AL amyloidosis may affect a person over time. These systems use blood test results that show stress or damage to the heart, such as troponin and NT-proBNP. Some also use results from echocardiograms.

Older AL amyloidosis staging systems include the Mayo 2012 system and the European-modified Mayo 2004 system. They group AL amyloidosis from stage 1 through stage 4. Stage 1 means earlier disease. Stage 4 means more-serious disease.

A newer system is the AL International Staging System (AL-ISS). It was created using information from people who received newer treatments. It groups AL amyloidosis from stage 1 through stage 3C. Stage 1 means earlier disease. Stage 3 means more-serious disease.

Staging systems continue to evolve as treatments improve. Your healthcare team can explain which system it uses and what your stage means for you.

The stage is only one part of your care. Your symptoms and other test results matter too. How well you do with treatment also matters.