Waldenstrom macroglobulinemia (NORD)
Definitions & Key takeaways
Waldenstrom Macroglobulinemia, or Waldenstrom syndrome, is a rare type of malignant lymphoma that's characterized by the overproduction of an antibody called immunoglobulin M (IgM) in the blood, which can lead to hyperviscosity syndrome (thickening of the blood) and interferes with normal blood circulation.
Symptoms can include fatigue, weakness, an enlarged spleen or lymph nodes, and bleeding or clotting problems. Diagnosis is through blood tests, bone marrow biopsy, and other imaging studies. Treatment options depend on the severity of the disease, as well as the patient's overall health and other individual factors. Options may include chemotherapy, targeted therapy, immunomodulatory drugs, stem cell transplantation, and supportive care.
Waldenstrom macroglobulinemia is a rare type of blood cancer that affects a specific type of white blood cell called B lymphocytes, which normally produce immunoglobulins like IgM.
This disease leads to high numbers of these cells in the bone marrow, which is located at the spongy center of some bones; as well as in lymphatic tissues, like the spleen and lymph nodes.
The increased number of B lymphocytes results in the production of high levels of IgM. This can ultimately cause the blood to become very thick, almost jelly-like, which prevents the normal, smooth blood flow throughout the body.Some of the signs and symptoms of Waldenstrom macroglobulinemia are caused by blood flow changes.
If there’s involvement of the retina, the inner lining of the eye, individuals may present with impaired or blurred vision.
Accumulation of B lymphocytes in the bone marrow can lead to anemia, which occurs when there aren’t enough red blood cells to deliver sufficient oxygen to body tissues.
As a result, individuals may experience fatigue and weakness. Patients may also experience tingling in the extremities, like fingers and toes.
Lastly, the immunoglobulins tend to accumulate in the lymph nodes, spleen, and liver, making these organs enlarge.B lymphocytes develop in the bone marrow.
As they become more mature, they leave the bone marrow and move into the blood and lymphatic tissues. Mature B lymphocytes produce specific proteins called antibodies, also known as immunoglobulins or Ig for short, which circulate around the body and help identify and fight off infections.
There are a few types of antibodies, one of which is IgM. Since it is the largest of the antibodies, it’s considered a macroglobulin.
In Waldenstrom macroglobulinemia, B lymphocytes do not function properly. They abnormally divide and accumulate in the bone marrow and lymphatic tissues.
This can cause blood vessels to tear. The underlying cause of the B lymphocytes’ abnormal behavior is unknown.
But it tends to occur more commonly in males than females; as well as in caucasian individuals; and in those who are over 50 years old.
Most people with Waldenstrom macroglobulinemia have a specific change, or mutation, in the MYD88 gene and 30-40% of affected people have a mutation in the CXCR4 gene.
These mutations occur in the Waldenstrom cells only and are not inherited.Waldenstrom macroglobulinemia can be diagnosed based on an individual’s signs and symptoms.
Often that includes having an enlarged liver and spleen, associated with retinal bleeding. A number of laboratory tests can also be used.
A blood test, called a complete blood count, is often performed. It can show low red blood cell numbers which indicates anemia; and a decrease in other blood components, like platelets.
Blood electrophoresis should be performed to look for the increased immunoglobulin concentration in the blood, known as an M spike.
Finally, a lymph node or bone marrow biopsy can be done to confirm the diagnosis. Treatment depends on the severity of the disorder.
If there are no symptoms, watchful waiting is recommended to closely monitor the disease progression. If the blood becomes too thick, it can be managed with plasmapheresis, a process in which plasma is separated from blood cells, to remove the excess IgM.
As the disorder progresses, red blood cell and platelet transfusions may be necessary to manage blood loss. Finally, chemotherapeutic medications, like rituximab, combined with other agents, can be used for treatment; while new therapies include bortezomib, ixazomib, carfilzomib, bendamustine and acalabrutinib; and ibrutinib and zanubrutinib, which were recently FDA approved for the treatment of Waldenstrom macroglobulinemia.
There is some evidence that patients with a CXCR4 mutation are more severely affected and do not respond as well to treatment.Waldenstrom macroglobulinemia is a rare type of blood cancer characterized by abnormally increased numbers of B lymphocytes, which produce high levels of immunoglobulins like IgM.
As a result, these immunoglobulins accumulate, causing the blood to become thick and preventing its normal flow. These blood changes lead to many of the signs and symptoms, which include bleeding, blurred vision, anemia, and improper blood flow to tissues.
A diagnosis can be made based on laboratory tests, such as blood electrophoresis which detects M spikes of immunoglobulin.
Treatment depends on severity of the disorder. If there are no symptoms, watchful waiting is recommended.
If the blood becomes too thick, it can be managed with plasmapheresis to remove the excess IgM; and chemotherapeutic agents may also be used.
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