Conditions > Waldenström disease

Waldenström disease

Clinical picture

Waldenström disease (also called Waldenström macroglobulinemia, or lymphoplasmacytic lymphoma) is a type of non-Hodgkin lymphoma. This cancer is characterised by an uncontrolled growth of a specific type of white blood cells (B lymphocytes), an important compound of the immune system, in the bone marrow. These aberrant B lymphocytes mature and accumulate in the bone marrow, the liver, and the spleen. The production of normal healthy cells will be inhibited, possibly leading to anaemia.

Some of the cancer cells make large amounts of a certain type of protein, called M protein (an IgM antibody). When abnormal amounts of this protein accumulate in the blood, the amount of normal antibodies in the blood can be reduced and bleeding can occur. Moreover, large amounts of the M-protein can make the blood thicker (hyperviscosity), which makes it difficult for the organs and tissues of the body to function properly. In some cases the M-protein is not produced properly, but in small, incomplete fractions. When these fractions are found in urine, they are called called Bence Jones proteins, or free light chains when found in the blood.

Waldenström disease was named after the Swedisch oncologist Jan Waldenström who reported two patients in 1944. Waldenström is an indolent lymphoma, indicating that the disease is a slow-growing blood cancer. In the Netherlands, about 150 individuals every year get Waldenström disease, more men than women. The mean age at diagnosis is 60 years. Waldenström is, after multiple myeloma, the second most frequent malignant disease in which plasma cells produce an aberrant M protein.

Symptoms

The course of Waldenström disease is slow in most patients. Consequently, it takes a while before symptoms appear. The disease is slowly progressive, which means that the gravity of the disease gradually increases. The most common symptoms are typically the same as those of other forms of non-Hodgkin lymphoma: weight loss, loss of appetite, fever, night sweats, swollen lymph nodes.

During the course of the disease, more lymphocytes accumulate in the bone marrow, liver, and spleen. As a consequence, the production of healthy red blood cells, white blood cells and blood platelets will be disrupted. Symptoms of a deficiency of red and white blood cells and blood platelets are:

Among which fatigue due to a low number of red blood cells.
Bleedings due to a low number of blood platelets.
High susceptibility to infections due to a low number of white blood cells (but also due to a low proportion of normal immunoglobulins).
Swollen lymph nodes, spleen, and liver due to proliferating lymphoma cells.

The aberrant amount of M protein can make the blood viscous (thick). This is called hyperviscosity, and can result in a reduced blood supply to the organs. Symptoms of a reduced blood flow are:

Vision problems: blurred vision, or bulging eyes due to damage of the small blood vessels in the eye.
Headache and dizziness.
Hearth problems through the fact that the heart has to work harder to pump the viscous blood through the body.
Blood circulation disturbances in the skin, ears, fingers, and toes.

In about 20% of patients, Waldenström disease affects the nerves. This so called neuropathy often starts at the far end of the long nerves: at the toes and finger tips. The main symptoms of neuropathy are:

Loss of strength in the hands or feet.
Tingling or numbness in the hands or the feet.

Cause

The cause of this disease is unknown.

Diagnosis

Waldenström disease is diagnosed after a physical examination and other tests:

Medical history.
Physical examination.
Laboratory tests in blood and urine.
- Complete blood count.
- 24-hour urine protein test: to detect the Bence Jones protein in the urine.
- Blood test: amount and type of immunoglobulin (IgM) in the blood serum.
- Blood and urine tests for kidney and liver function. The liver function can be declined because of the deposition of M protein (amyloidosis and hyperviscosity).
Bone marrow biopsy: microscopic examination of bone marrow tissue for the amount of lymphoplasmacytic cells in the bone marrow (in Waldenström patients frequently 10% of bone marrow cells).

Radiological examination/CT scan or ultrasound scan for enlarged lymph nodes.

Treatment

Waldenström disease is treatable, however, full recovery is not possible from this the disease. Given the slow-growing nature of this disease, observation is typically warranted. When complaints detoriate, the following treatments are available:

Treatment with one or more drugs is possible:
- Cell-killing (cytostatic) drugs such as chlorambucil, fludarabine and/or cyclophosphamide.
- Less intensive chemotherapy with CVP (cyclophosphamide, vincristine, prednisone).
- Intensive combined chemotherapy with CHOP (cyclophosphamide, (hydroxy)doxorubicin, vincristine and prednisone).
- Monoclonal antibodies such as rituximab, aiming at reducing the tumour mass without interfering with the production of healthy blood cells.
Plasmapheresis in order to filter M proteins from the blood in the case of hyperviscosity.
Radiation therapy to lymph nodes, if lymph nodes cause symptoms due to their position or magnitude.
Intensive chemotherapy followed by stem cell transplantation.
Treatment of cryoglobulinemia through preventive measures (prevention of exposure to cold), pain relief with NSAIDs and low dose steroids.
Treatment of Raynaud’s phenomenon with vasodilators (widening of blood vessels), such as nifedipine and prazosin.
Treatment of polyneuropathy with plasmapheresis, interferon alpha or rituximab. Unfortunately, successful treatment of Waldenström disease rarely leads to improvement of polyneuropathy.
Targeted therapy with monoclonal antibodies, kinase and proteasome inhibitors.