Waldenstrom’s macroglobulinemia, also known as WM or lymphoplasmacytic lymphoma, is a form of non-Hodgkin lymphoma (NHL). It is called WM when diagnosed in the blood and referred to as lymphoplasmacytic lymphoma when diagnosed through tests in the blood. Lymphoma is a blood cancer, similar to other related disorders such as leukemia, myeloma, and myeloproliferative neoplasms (MPNs).

Many symptoms of non-Hodgkin lymphoma overlap with those of Hodgkin lymphoma. Both affect the lymphatic system, which consists of bone marrow, lymph nodes, the spleen, and the thymus. In people with non-Hodgkin lymphoma, blood cells known as lymphocytes develop abnormally.

In WM, cancer cells create large quantities of abnormal proteins known as macroglobulins. This can cause symptoms that are hard to live with.

“[I] still tire easily,” a MyLymphomaTeam member wrote. “Lots of bone and joint pain, digestive issues, bruising, [and] red spots on my skin.”

“I have nerve pain in my shoulder and bicep,” one member posted.

“Mostly, I feel pretty well, although some degree of fatigue is always present,” another member commented.

What Is Waldenstrom’s Macroglobulinemia?

Waldenstrom’s macroglobulinemia is a sister disease to multiple myeloma. It can cause symptoms such as fever, night sweats, swollen lymph nodes, and weight loss — these all overlap with non-Hodgkin lymphoma symptoms.

Other symptoms of WM result from large amounts of abnormal immunoglobulin M (IgM) antibodies, known as M proteins, being created by cancer cells. These include hyperviscosity syndrome, in which excess amounts of M protein in the blood cause it to thicken. This can cause poor circulation to the brain and lead to symptoms similar to those experienced by people who have had a stroke.

If the M protein thickens blood only in the body’s extremities — ears, fingers, or toes — it can result in a condition known as cryoglobulinemia, which can cause pain for people with Waldenstrom’s macroglobulinemia. Another condition, known as amyloidosis, occurs when a protein component known as a light chain — which is part of the IgM antibody — builds up in the heart or kidneys.

B Cell or T Cell? Indolent or Aggressive?

Waldenstrom’s macroglobulinemia originates in the B cells, also known as B lymphocytes. When functioning normally, these white blood cells fight infection by transforming into plasma cells, making proteins called antibodies, or immunoglobulins. These cells help the body ward off bacteria that can cause diseases. T cells, on the other hand, direct the immune system to kill germs.

WM is an indolent cancer, as opposed to an aggressive cancer. This means that the growth rate of this B-cell lymphoma is slow, and although there’s no cure for WM, it can be treated with specific therapies.

Prevalence and Prognosis

Waldenstrom’s macroglobulinemia is a rare condition. Approximately 1,000 to 1,500 adults in the United States receive a WM diagnosis every year, or six cases per million people. The average age of people diagnosed with WM is 70, and the chance of developing it increases with age. It is more common in men than in women.

Many people with WM initially present with hyperviscosity, which is a potential crisis. However, it can be addressed with proper treatment. Fortunately, WM is easy to diagnose with a blood test and is easy to treat.

The five-year survival rate for people with Waldenstrom’s macroglobulinemia is approximately 78 percent. An individual’s prognosis depends on risk factors such as age, hemoglobin levels, microglobulin levels, platelet count, and high IgM serum levels.

Causes

Despite great strides made in cancer research, clinical oncology, and hematology in recent years, the precise cause of Waldenstrom’s macroglobulinemia remains unknown. However, it typically begins when the genetic code of an abnormal white blood cell mutates. The cell multiplies quickly, and the new cancer cells eventually overwhelm the healthy cells.

The cancerous cells then begin to crowd out healthy blood cells in the bone marrow, leading to low levels of red blood cells. WM cells will continue to try and produce antibodies, but instead, they will produce abnormal proteins. A protein called immunoglobulin M, or IgM, will then accumulate in the blood, where it slows circulation and leads to complications.

Research suggests that a mutation of the MYD88 gene may contribute to WM.

Diagnosis

Two tests are typically used to diagnose Waldenstrom’s macroglobulinemia — blood tests and imaging tests.

A blood test can reveal that a person has low numbers of healthy blood cells, and it can be used to detect IgM proteins. Blood tests can also gauge organ function, which lets health care providers know whether those proteins affect kidney or liver function. Imaging tests, such as computerized tomography (CT) scans or positron emission tomography (PET) scans, will reveal if the cancer has spread.

People will come to the emergency room in some cases, believing that they’re suffering a heart attack due to chest pains. In these cases, blood tests are critical to understanding the hematologic condition that the person is experiencing.

Waldenstrom’s macroglobulinemia is not a common illness. The majority of people who show up in the hospital with chest pain need to see a cardiologist and not a hematologist. Hopefully, a doctor who has a sense of the larger picture of potential causes of chest pain would notice that the protein levels in the routine blood test were high, that the blood counts were low, or another clue, and test for the M protein.

If the test results are inconclusive, doctors can also perform a bone marrow biopsy, in which a needle is used to take a sample of bone marrow. This sample is then analyzed for signs of cancer cells.

Once a doctor performs the bone marrow examination, and the condition is correctly identified as WM, people can receive the correct treatment. Occasionally, the diagnosis of lymphoplasmacytic lymphoma leads to testing that also produces the diagnosis of WM.

Symptoms

As an indolent cancer, Waldenstrom’s macroglobulinemia grows slowly and may avoid detection for a long time simply because no symptoms have emerged. When they do, they can include:

• Bleeding gums or nose
• Bruising easily
• Confusion
• Fatigue
• Fever
• Headache
• Numbness of the feet or hands
• Shortness of breath
• Vision changes
• Weight loss

People with WM can display signs of severe cardiac illness beyond these symptoms due to a high IgM level.

Read more about the signs and symptoms of Waldenstrom's macroglobulinemia.

Treatments

Although there is no cure for Waldenstrom’s macroglobulinemia, several treatment options exist. These include biological therapy drugs, which can be used alone or in conjunction with other treatments, such as monoclonal antibodies (for example, Rituxan [rituximab]). Targeted therapy is also an option.

In some cases, bone marrow transplantation, known as stem cell transplantation, may be appropriate. In these instances, chemotherapy kills diseased bone marrow. This is followed by the infusion of healthy blood stem cells, which create healthy new bone marrow.

Chemotherapy may also be used, either alone or in combination with other treatments. A plasma exchange, or plasmapheresis, may also be appropriate. This process is used when the blood is too thick and excess M protein needs to be removed from it. Killing the blood cells that create the IgM antibody can often involve using medicines used to treat other illnesses.

Currently, a clinical trial being conducted by the Institute of Hematology and Blood Diseases Hospital is studying the effect of an oral regimen that targets lymphoma cells and plasma cells to eliminate WM tumor cells. The regimen combines Ozurdex (dexamethasone), Ninlaro (ixazomib), and Brukinsa (zanubrutinib). Brukinsa had recently been FDA approved, but for a different condition, called mantle cell lymphoma. Previous studies have suggested that a regimen of Ozurdex, Rituxan, and cyclophosphamide may also benefit people with WM.

Read more about treatments for Waldenstrom’s macroglobulinemia.

You Are Not Alone With Waldenstrom’s Macroglobulinemia

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How does Waldenstrom’s macroglobulinemia affect your daily life? Has your health care provider found the right treatment options to manage your Waldenstrom’s macroglobulinemia? Share your tips and experiences in a comment below or on MyLymphomaTeam.