What is Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia)?
Lymphoplasmacytic lymphoma, also known as Waldenstrom macroglobulinemia, is a type of slow-growing cancer affecting B cells, a type of white blood cell. This condition features a mix of small white blood cells and an abnormal protein known as IgM monoclonal gammopathy. People with this illness typically experience symptoms related to bone marrow invasion and the buildup of the abnormal protein.
However, diagnosing lymphoplasmacytic lymphoma isn’t straightforward; it must be diagnosed by ruling out all other similar types of B cell cancers first. The condition was first described by Jan G. Waldenstrom in 1944 who noticed an unusual combination of symptoms in two patients: enlarged lymph nodes (lymphadenopathy), bleeding instability, low red blood cell count (anemia), faster than normal blood cell sedimentation rate, thickened blood (hyperviscosity), and unusually high levels of proteins in the blood (hypergammaglobulinemia).
What Causes Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia)?
The exact cause of a disease known as lymphoplasmacytic lymphoma is not completely clear. Nevertheless, it is known to be associated with hepatitis C virus and conditions where the immune system attacks the body’s own cells, known as autoimmune disorders. As a form of treatment, patients with lymphoplasmacytic lymphoma who also have hepatitis C can benefit from medicines that kill viruses.
It has also been found that about 20% of people with lymphoplasmacytic lymphoma might have a family history of the disease. These patients often are diagnosed at a younger age and have a higher amount of involvement in their bone marrow, the soft, spongy tissue inside your bones that produces new blood cells.
Scientists are interested in understanding the potential impact on the outlook of the disease due to genetic susceptibility in lymphoplasmacytic lymphoma. This means they’re researching whether certain genes might make people more likely to develop the disease and how this affects the chances of recovery and survival.
Risk Factors and Frequency for Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia)
Lymphoplasmacytic lymphoma is a very rare type of cancer. It affects a small number of people each year and represents a small fraction of all blood-related cancers. In the United States, between 1000 and 1500 new cases are reported annually. This disease typically affects older people, particularly those in their 70s and 80s, and is slightly more common in men. It generally progresses slowly, and most patients live for 7 to 8 years after their diagnosis. However, in rare situations, lymphoplasmacytic lymphoma can evolve into a more aggressive type of cancer.
- Lymphoplasmacytic lymphoma is a very rare type of cancer.
- It affects 3-4 people in a million every year and makes up about 2% of all blood cancers.
- In the United States, there are 1000-1500 new cases each year.
- It is generally seen in older people, especially those in their 70s and 80s.
- Men are slightly more likely to get it than women.
- It usually progresses slowly, but in rare cases, it can evolve into a more aggressive type of cancer.
- Most patients live for 7-8 years after being diagnosed.
Signs and Symptoms of Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia)
Lymphoplasmacytic lymphoma, also known as Waldenstrom macroglobulinemia, is a complex condition to diagnose. This difficulty arises due to a lack of clear physical, immunological, or genetic markers, and it makes distinguishing this disease from other similar ones a process of elimination. Symptoms could come from either the growth of the disease itself or from the effects of IgM, a type of protein that increases in those with the condition.
Typically, patients may experience symptoms such as fever, night sweats, and weight loss. Many patients might report weakness or fatigue, which are often due to anemia caused by the disease’s frequent impact on bone marrow. In some cases, the condition might affect organs outside of the lymph nodes, such as the spleen, liver, skin, stomach, and bowel. The condition should be suspected in elderly individuals presenting unexplained weakness, bleeding, neurological issues, nerve damage, and vision problems.
The 2017 World Health Organization’s classification for tumors of hematopoietic and lymphoid tissues identifies four key diagnostic criteria for Waldenstrom macroglobulinemia:
- The presence of IgM monoclonal gammopathy
- Infiltration of bone marrow by small lymphocytes exhibiting plasmacytoid or plasma cell evolution
- Bone marrow infiltration following an intertrabecular pattern
- Immunophenotype signals supportive of Waldenstrom macroglobulinemia, including positive results for a series of specific markers
Typically, patients with Waldenstrom macroglobulinemia have an increase in a type of protein called monoclonal IgM. A few might also have an elevation in IgG as well. Symptoms can vary from hyperviscosity – affecting vision and neurological functions to autoimmune hemolysis – causing coagulation issues and diarrhea. In cases of hyperviscosity, patients might experience vision impairment, nerve-related symptoms, bleeding, new headaches, and blurred vision. Autoimmune hemolysis in these patients is often due to cold agglutinins – a type of IgM antibody that activates at lower temperatures.
Testing for Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia)
Lymphoplasmacytic lymphoma is a type of cancer that affects small white blood cells, known as lymphocytes. This condition is diagnosed by looking for these malignant (or harmful) lymphocytes within the marrow of our bones. These cells are often mixed with other cell types such as plasma cells or mast cells.
The structure of our bone marrow where these cells can be found can vary in patients with lymphoplasmacytic lymphoma – it can be spread throughout the marrow, scattered in different pockets, or grouped along trabeculae, which are supportive tissues found in the bone marrow.
When these diseased cells spread to our lymph nodes, the nodes generally maintain their overall structure, but also see an expansion of the lymphocyte population and a dilation of their sinuses, which are channels for lymph fluid. Other features like Dutcher Bodies, which are little areas inside the cells carrying protein materials, the higher presence of mast cells, which are involved in allergic reactions, or hemosiderin deposits, a form of stored iron, can assist in diagnosing the disease.
In some cases, there might be deposits of amyloids, or abnormal proteins, and in rare instances, there are other types of immunoglobulins, which are antibodies produced by our immune system. However, if there are significant numbers of large cells with prominent features, it might suggest a different diagnosis.
Complete blood counts in patients with lymphoplasmacytic lymphoma often reveal low numbers of different types of blood cells. Patients commonly exhibit anemia and thrombocytopenia, which refer to low red blood cell and blood clotting cell (platelets) counts respectively. Characteristics of the blood cells, specifically the presence or absence of certain proteins on the cell surface, which are determined through a process called flow cytometry, and the analysis of proteins, specifically the type of antibody (paraprotein), in the blood can provide further insights into the disease.
Genetic studies of lymphoplasmacytic lymphoma usually show alterations and defects in the genes of the immune system. An abnormality in a gene called MYD88 is often present, but is not necessary for the diagnosis, as this gene can also be abnormal in other types of lymphomas, including certain subtypes of diffuse large B-cell lymphoma (DLBCL), a more aggressive form of lymphoma. Other genes may also show alterations in lymphoplasmacytic lymphoma.
When the disease seems to be spreading beyond the bone marrow to other organs such as the liver and spleen (a condition known as extramedullary disease), doctors might order contrast-enhanced CT scans, which are imaging tests that use a special dye to help visualize the organs better. These scans are useful in tracking the progression of the disease and assessing the effectiveness of treatment.
Treatment Options for Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia)
When it comes to managing Lymphoplasmacytic lymphoma, a slow-growing type of blood cancer, the strategies used are often similar to those used to treat other slow-growing B cell lymphomas (cancers of the white blood cells). If a patient does not have any symptoms, doctors usually choose to closely monitor their condition rather than start treatment right away. On the other hand, symptomatic patients are typically treated with a medicine called rituximab, which targets and kills the cancer cells.
Waldenstrom macroglobulinemia is a specific type of Lymphoplasmacytic lymphoma. In this condition, too much of a certain protein (called IgM) is produced, which can thicken the blood and cause it to flow more slowly than normal. The treatment plan for this disease largely depends on how much damage the disease has done to the body and the severity of the symptoms. Like with Lymphoplasmacytic lymphoma, patients with Waldenstrom macroglobulinemia who have no symptoms can also be closely monitored and have their IgM levels and blood thickness checked regularly. However, if they do have symptoms, they may need chemotherapy, immunotherapy (which boosts the immune system to fight cancer), or even a bone marrow stem cell transplant.
There are several types of chemotherapy medicines which have been found to be effective against Waldenstrom macroglobulinemia, including dexamethasone, fludarabine, bortezomib, and cyclophosphamide. A bone marrow transplant is generally only considered for younger patients who have serious bone marrow involvement.
The common treatment plan for Waldenstrom macroglobulinemia involves using rituximab together with a chemotherapy drug called bendamustine. If this doesn’t work, or if the disease comes back within three years, then other treatments such as bortezomib, cyclophosphamide, or ibrutinib might be considered. Further lines of treatment can include fludarabine, everolimus, or lenalidomide. There is also a procedure called plasmapheresis, which can be used to help manage the thickness of the blood caused by the excess protein.
What else can Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia) be?
These are different types of illnesses that are related to lymphocytes, a specific type of white blood cell:
- Chronic lymphocytic leukemia/small lymphocytic lymphoma
- Mantle cell lymphoma
- Marginal zone lymphoma
- Plasma cell neoplasms
- Castleman disease
- Reactive plasmacytosis
What to expect with Lymphoplasmacytic Lymphoma (Waldenstrom Macroglobulinemia)
Patients with a type of cancer called lymphoplasmacytic lymphoma typically live about five years on average, although around 40% of them can expect to live ten years or more. It should be noted that usually the cause of death in these patients is not the cancer itself, but other medical conditions that come with advanced age.
Doctors use a system called the International Prognostic Scoring System to predict how the disease might progress in patients with this type of cancer. This system uses five factors to calculate a score, such as age (with individuals older than 65 years receiving 2 points), levels of hemoglobin (a protein in blood cells that carries oxygen), platelet count (tiny blood cells that help your body form clots to stop bleeding), B microglobulin and serum monoclonal protein levels (both of which are related to disease activity).
Based on their score, patients can be grouped into low risk (score of 1 or less), intermediate risk (score of 2), or high risk (score of 3 or more). For these groups, the expected 5-year survival rates are 87%, 68% and 36% respectively.
Some other factors, like the presence of certain cells called immunoblasts and genetic changes such as the deletion of a chromosome region named 6q, are associated with a worse outcome. If a patient doesn’t carry a particular gene mutation called MYD88 L265P, this is also seen as a negative factor.
It might also happen that lymphoplasmacytic lymphoma may progress into another type of cancer called diffuse large B-cell lymphoma, and this is associated with poorer survival rates.
