Waldenstrom’s Macroglobulinaemia

Waldenstrom’s macroglobulinaemia is a rare, slow-growing blood cancer that affects white blood cells and causes production of an abnormal protein that can thicken the blood, making it harder to flow through blood vessels.

Table of contents

• What is Waldenstrom’s Macroglobulinaemia?
• Symptoms
• Causes and Risk Factors
• Complications
• Diagnosis
• Treatment Options
• Living with the Condition

What is Waldenstrom’s Macroglobulinaemia?

Waldenstrom’s macroglobulinaemia (also known as lymphoplasmacytic lymphoma) is a rare type of blood cancer^[1]. It affects about 3 to 4 out of every 1 million people in the United States each year, with approximately 1,000 to 1,500 new cases diagnosed annually^[2][8].

This condition is a form of non-Hodgkin lymphoma, which means it is a cancer that starts in white blood cells called lymphocytes^[1]. In Waldenstrom’s macroglobulinaemia, certain white blood cells called B cells undergo changes that turn them into cancer cells^[1]. These cancer cells build up mainly in the bone marrow, the spongy tissue inside bones where blood cells are made^[1].

The condition grows slowly and may not cause symptoms for years^[1]. The cancer cells can crowd out healthy blood cells in the bone marrow, which can lead to low numbers of red blood cells (causing anemia), white blood cells, and platelets^[2]. The cancer cells also produce large amounts of an abnormal protein called immunoglobulin M (IgM). When too much of this protein builds up in the blood, it can make the blood thicker than normal, like syrup, which makes it harder for blood to flow through small blood vessels^[1][2].

While there is no cure for Waldenstrom’s macroglobulinaemia, there are treatments that can help manage symptoms and keep the disease under control, sometimes for many years^[2][6].

lymphoplasmacytic lymphoma, LPL, WM

• Bone marrow
• Lymph nodes
• Spleen

Symptoms

Many people with Waldenstrom’s macroglobulinaemia do not have symptoms when first diagnosed. In fact, one in four people learn they have this condition during medical visits for other reasons^[2][6]. When symptoms do appear, they develop slowly over time^[1].

Common symptoms include feeling very tired and weak, fever, loss of appetite, night sweats, and losing weight without trying^[1][2]. Some people may notice swollen lymph nodes or feel fullness or pain under the ribs on the left side, which can happen when the spleen becomes enlarged^[1].

The condition can cause numbness or tingling in the hands and feet, a problem known as peripheral neuropathy^[1][2]. Some people experience easy bruising, bleeding from the nose or gums, headaches, shortness of breath, changes in vision, or confusion^[1][2]. These last symptoms can happen when the blood becomes too thick due to the buildup of the IgM protein^[2].

Causes and Risk Factors

Waldenstrom’s macroglobulinaemia is caused by changes in genes inside B cells^[2]. More than 90% of people with this condition have a change in a gene called MYD88, and about 40% have changes in another gene called CXCR4^[2][6]. These genetic changes help the abnormal cells multiply^[2].

The genetic changes that cause Waldenstrom’s macroglobulinaemia are not inherited from parents and cannot be passed on to children. They happen during a person’s lifetime, though scientists do not yet know what triggers these changes^[2].

Several factors may increase the chance of developing this condition. It is most common in people who are 65 years old or older^[2]. Men are more likely to develop the condition than women, and it is most common in people who are white^[2][6].

Having certain other health conditions may increase risk, including hepatitis C, AIDS, Sjögren’s syndrome, or a condition called MGUS (monoclonal gammopathy of undetermined significance)^[2]. MGUS is considered a precursor to Waldenstrom’s macroglobulinaemia, though not everyone with MGUS will develop the disease^[2]. Having family members with Waldenstrom’s macroglobulinaemia or other types of lymphoma may also increase risk^[2].

Complications

In severe cases, Waldenstrom’s macroglobulinaemia can lead to serious complications^[2]. One important complication is amyloidosis, which happens when faulty proteins build up in organs such as the heart, lungs, and kidneys^[2].

Another complication is cryoglobulinemia, a condition where certain blood proteins that react to cold gather in clumps in the hands and feet^[2]. This can cause pain and may turn the hands and feet blue or white^[2].

The thick blood caused by too much IgM protein can lead to hyperviscosity syndrome, which can cause bleeding problems, vision problems, and problems with the nervous system^[6].

Diagnosis

Doctors use several tests to diagnose Waldenstrom’s macroglobulinaemia^[11]. A physical exam and review of medical history are important first steps^[11].

Blood tests can show if there are too few healthy blood cells and can detect the IgM protein made by cancer cells^[11]. Blood tests also show how well organs such as the kidneys and liver are working^[11].

A bone marrow biopsy is a key test where a needle is used to take a sample of bone marrow, usually from the hipbone^[11]. The sample is examined in a laboratory to look for cancer cells and to learn more about them^[11].

Imaging tests such as CT scans or PET scans may be used to see if cancer has spread to other areas of the body^[11].

Treatment Options

Treatment for Waldenstrom’s macroglobulinaemia depends on whether the disease is causing symptoms and how quickly it is progressing^[9]. Because this condition grows slowly, not everyone needs treatment right away^[9].

Watchful Waiting

If the disease is developing slowly and not causing symptoms, doctors may recommend watchful waiting (also called active surveillance)^[9][16]. During this time, the healthcare team will closely monitor the condition with regular tests. Treatment begins when symptoms appear or when there are signs the disease is progressing more quickly^[16].

Plasmapheresis

Some patients may need a procedure called plasmapheresis to temporarily reduce symptoms caused by thick blood^[9][16]. During this procedure, blood is removed from the body, passed through a machine that removes the part containing the IgM protein, and then returned to the body^[9].

Targeted Therapy

Targeted therapy uses drugs that work on specific molecules on or inside cancer cells^[16]. These drugs can stop the growth and spread of cancer cells while causing less harm to normal cells^[16].

Several targeted therapy drugs are used for Waldenstrom’s macroglobulinaemia. Rituximab is commonly combined with other drugs^[16]. Ibrutinib was the first therapy approved specifically for this condition in 2015^[9]. Other drugs in this category include acalabrutinib, zanubrutinib, bortezomib, and lenalidomide^[16].

Chemotherapy

Chemotherapy uses drugs to destroy cancer cells^[16]. Several chemotherapy drugs may be used, including bendamustine, fludarabine, cyclophosphamide, chlorambucil, and cladribine^[16]. These drugs are often combined with targeted therapy drugs or steroid medications such as dexamethasone or prednisone^[16].

Common combinations of drugs include bendamustine and rituximab (BR), cyclophosphamide with dexamethasone and rituximab (DRC), and bortezomib with rituximab^[16][9].

The choice of treatment depends on individual patient needs, including age, overall health, the severity of symptoms, and consideration of both short-term and long-term side effects^[9][13].

Living with the Condition

Learning to live with Waldenstrom’s macroglobulinaemia involves making healthy lifestyle choices and getting proper support^[17].

Diet and Nutrition

Eating a healthy, balanced diet with plenty of fruits, vegetables, protein, and whole grains can help you feel better^[18][19]. There are no special diets proven to help with Waldenstrom’s macroglobulinaemia, but a varied diet provides the nutrients your body needs^[23]. During chemotherapy, you may need to follow a special “neutropenic” diet when white blood cell counts are low^[23].

Some people with this condition may have vitamin deficiencies, particularly vitamin B12, folate, vitamin D, or iron^[23]. These can be easily checked with blood tests and replaced with supplements or injections if needed^[23].

Managing Fatigue

Fatigue is one of the most common symptoms experienced by people with cancer^[18]. This tiredness is different from everyday tiredness and usually lasts longer. Fatigue can be related to pain, anxiety, medications, nutritional deficiencies, or lack of activity^[18].

It helps to track when you feel energized and when you feel exhausted, then plan activities for times when you have more energy^[18]. Don’t hesitate to ask for help from others, especially when feeling low on energy^[18].

Preventing Infections

Staying safe from infections is very important, especially during treatment^[23]. Simple steps like washing hands regularly, wearing a mask in crowded places, and avoiding people who are sick can help prevent infections^[23].

Emotional Support

Receiving a cancer diagnosis can be frightening and overwhelming^[23]. Many people feel shocked when diagnosed with a rare disease with a difficult name^[23]. It is very helpful to connect with sources of reliable information and support^[23].

Reaching out to family and friends for support is important while managing this disease^[6]. Support groups, either in person or online, can connect you with others who understand what you are going through^[17].

Medical Care Follow-up

Regular follow-up with your healthcare team is essential^[24]. Make sure you understand your treatment plan and medications. Keep records of your discussions, medications, and treatments^[23]. Don’t feel shy about asking questions to help you stay safe and well^[23].