1. What is Waldenström macroglobulinemia?

Waldenström macroglobulinemia (WM) is a rare, indolent (slow-growing) non-Hodgkin lymphoma (cancer that begins in the cells of the immune system). WM is also called lymphoplasmacytic lymphoma. It starts in white blood cells called B lymphocytes or B cells.

B cells are an important part of the body’s immune system. They form in the lymph nodes, spleen, and other lymphoid tissues, including bone marrow (the soft, spongy tissue inside bones). Some B cells become plasma cells, which make, store, and release antibodies. Antibodies help the body fight viruses, bacteria, and other foreign substances.

Lymphoplasmacytic cells are cells that are in the process of maturing from B cells to plasma cells. In WM, abnormal lymphoplasmacytic cells multiply out of control, producing large amounts of a protein called monoclonal immunoglobulin M (IgM or “macroglobulin”) antibody. High levels of IgM in the blood cause hyperviscosity (thickness or gumminess), which leads to many of the symptoms of WM (see Question 4).

2. How often does Waldenström macroglobulinemia occur?

WM is a rare cancer; about 1,500 new cases occur annually in the United States. The incidence of WM is higher in males and higher in whites than in African Americans. Incidence increases sharply with age. The median age at diagnosis is 63 (half of the cases are diagnosed before age 63, and half are diagnosed after age 63) (1).

3. What are the possible causes of Waldenström macroglobulinemia?

The exact cause of WM is not known. However, scientists believe that genetics may play a role in WM, because the disease has been seen to run in families (1).

4. What are the symptoms of Waldenström macroglobulinemia?

Some patients do not have symptoms. For those who do have symptoms, the most common ones are weakness, severe fatigue, bleeding from the nose or gums, weight loss, and bruises or other skin lesions. Severely high levels of IgM can lead to hyperviscosity syndrome, in which the blood becomes abnormally thick. Symptoms of this syndrome include visual problems (e.g., blurring or loss of vision) and neurological problems (e.g., headache, dizziness, vertigo). During a physical exam, a doctor may also find swelling of the lymph nodes, spleen, and/or liver (2).

5. How is Waldenström macroglobulinemia diagnosed?

Initial diagnosis of WM is based on blood test and bone marrow biopsy results. Blood tests are used to determine the level of IgM in the blood and the presence of proteins, or tumor markers, that can indicate WM. For the biopsy, a sample of bone marrow (soft, sponge-like tissue in the center of most bones) is removed, usually from the back of the pelvis bone, through a needle for examination under a microscope. The pathologist (a doctor who identifies diseases by studying cells and tissue under a microscope) looks for certain types of lymphocytes (white blood cells) that indicate WM (1). Flow cytometry (a method of measuring cell properties using a light-sensitive dye and laser or other type of light) is often used to look at markers on the cell surface or inside the lymphocytes.

Additional tests may be recommended to confirm the diagnosis. A computed tomography (CT or CAT) scan uses a computer linked to an x-ray machine to create pictures of areas inside the body. This test may be used to evaluate the chest, abdomen, and pelvis, particularly swelling of the lymph nodes, liver, and/or spleen (1). A skeletal survey (x-rays of the skeleton) can help distinguish between WM and a similar plasma cell cancer, multiple myeloma (1).

6. How is Waldenström macroglobulinemia treated?

At this time, there is no known cure for WM. However, several treatment options are available to prevent or control the symptoms of the disease.

Patients who do not have symptoms of WM are usually monitored without being treated; these patients often live for many years before requiring treatment (2). Patients with symptoms are usually treated with chemotherapy. Biological therapy (treatment that stimulates the immune system to fight cancer) is also used to treat WM (3). Promising results have been seen with biological therapy and chemotherapy in combination. An example of combination therapy uses rituximab and fludarabine (4). Patients with high levels of IgM and hyperviscosity syndrome may undergo plasmapheresis. In this procedure, blood from the patient is removed and circulated through a machine that separates the plasma (which contains the antibody IgM) from other parts of the blood (red blood cells, white blood cells, and platelets). The red and white blood cells and platelets are returned to the patient, along with a plasma substitute (4). Plasmapheresis is often followed by chemotherapy.

Because WM is rare, some doctors may suggest treatments that have been effective in some cases but are not considered standard treatment and/or are under study in clinical trials (research studies). Some of these treatments include (4):

• High-dose chemotherapy with autologous stem cell transplantation— blood-forming stem cells (cells from which all blood cells develop) are harvested (removed) and stored, then given back to the patient following high-dose chemotherapy. The harvested cells may be treated before transplantation to get rid of cancer cells. The transplanted cells travel to the bone marrow and begin to produce new blood cells.
  
  
• Splenectomy—surgery to remove the spleen. This procedure has been used in WM patients who have a significantly enlarged spleen. Occasionally, WM patients who have had this procedure have experienced remissions (decrease in or disappearance of signs or symptoms of cancer) lasting for many years. The remissions are believed to be due to the removal of a major source of IgM production.
  
  
• Thalidomide and bortezomib—drugs used to treat multiple myeloma, a disease similar to WM. Side effects of thalidomide include constipation, weakness, and peripheral neuropathy (a problem in nerve function that causes pain, numbness, tingling, swelling, and muscle weakness). Both agents are currently being studied in clinical trials for WM.
  
  
7. Are clinical trials (research studies) available? Where can people get more information about clinical trials?

Yes. The National Cancer Institute (NCI), a component of the National Institutes of Health, is sponsoring clinical trials that are designed to find new treatments and better ways to use current treatments. Before any new treatment can be recommended for general use, doctors conduct clinical trials to find out whether the treatment is safe for patients and effective against the disease. Participation in clinical trials may be a treatment option for patients with WM.

People interested in taking part in a clinical trial should talk with their doctor. Information about clinical trials is available from the NCI’s Cancer Information Service (CIS) (see below) at 1–800–4–CANCER and in the NCI booklet Taking Part in Cancer Treatment Research Studies, which can be found at http://www.cancer.gov/publications on the Internet. This booklet describes how research studies are carried out and explains their possible benefits and risks. Further information about clinical trials is available at http://www.cancer.gov/clinicaltrials on the NCI’s Web site. The Web site offers detailed information about specific ongoing studies by linking to PDQ^®, the NCI’s comprehensive cancer information database. The CIS also provides information from PDQ.

 

Selected References

1. Munshi NC, Anderson KC. Plasma cell neoplasms. In: DeVita VT Jr., Hellman S, Rosenberg SA, editors. Cancer: Principles and Practice of Oncology. Vol. 2. 7th ed. Philadelphia: Lippincott Williams and Wilkins, 2004.

2. Richardson P, Hideshima T, Anderson KC. Multiple myeloma and related disorders. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, editors. Clinical Oncology. 3rd ed. London: Churchill Livingstone, 2004.

3. Gertz MA, Anagnostopoulos A, Anderson K, et al. Treatment recommendations in Waldenstrom’s macroglobulinemia: Consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia. Seminars in Oncology 2003; 30(2):121–126.

4. Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP. Diagnosis and management of Waldenstrom’s macroglobulinemia. Journal of Clinical Oncology 2005; 23(7):1564–1577.

Related NCI materials and Web pages:

• National Cancer Institute Fact Sheet 5.2,
  Computed Tomography (CT): Questions and Answers ¹
  (http://www.cancer.gov/cancertopics/factsheet/Detection/CT)
• National Cancer Institute Fact Sheet 5.18,
  Tumor Markers: Questions and Answers ²
  (http://www.cancer.gov/cancertopics/factsheet/Detection/tumor-markers)
• National Cancer Institute Fact Sheet 7.2,
  Biological Therapies for Cancer: Questions and Answers ³
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/biological)
• National Cancer Institute Fact Sheet 7.49,
  Targeted Cancer Therapies: Questions and Answers ⁴
  (http://www.cancer.gov/cancertopics/factsheet/Therapy/targeted)
• Biological Therapy: Treatments That Use Your Immune System To Fight Cancer ⁵
  (http://www.cancer.gov/cancertopics/biologicaltherapy)
• Chemotherapy and You: Support for People With Cancer ⁶
  (http://www.cancer.gov/cancertopics/chemotherapy-and-you)
• Taking Part in Cancer Treatment Research Studies ⁷
  (http://www.cancer.gov/clinicaltrials/Taking-Part-in-Cancer-
  Treatment-Research-Studies)
• Non-Hodgkin Lymphoma Home Page ⁸
  (http://www.cancer.gov/cancertopics/types/non-hodgkins-lymphoma)

NCI’s Cancer Information Service
Telephone (toll-free): 1–800–4–CANCER (1–800–422–6237)
TTY (toll-free): 1–800–332–8615
LiveHelp^® online chat: https://cissecure.nci.nih.gov/livehelp/welcome.asp

Glossary Terms

The area of the body that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs.

Not normal. An abnormal lesion or growth may be cancerous, premalignant (likely to become cancer), or benign.

A type of protein made by plasma cells (a type of white blood cell) in response to an antigen (foreign substance). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.

A procedure in which blood-forming stem cells (cells from which all blood cells develop) are removed, stored, and later given back to the same person.

A type of immune cell that makes proteins called antibodies, which bind to microorganisms and other foreign substances, and help fight infections. A B lymphocyte is a type of white blood cell. Also called B cell.

A large group of single-cell microorganisms. Some cause infections and disease in animals and humans. The singular of bacteria is bacterium.

Treatment to boost or restore the ability of the immune system to fight cancer, infections, and other diseases. Also used to lessen certain side effects that may be caused by some cancer treatments. Agents used in biological therapy include monoclonal antibodies, growth factors, and vaccines. These agents may also have a direct antitumor effect. Also called biological response modifier therapy, biotherapy, BRM therapy, and immunotherapy.

The removal of cells or tissues for examination by a pathologist. The pathologist may study the tissue under a microscope or perform other tests on the cells or tissue. There are many different types of biopsy procedures. The most common types include: (1) incisional biopsy, in which only a sample of tissue is removed; (2) excisional biopsy, in which an entire lump or suspicious area is removed; and (3) needle biopsy, in which a sample of tissue or fluid is removed with a needle. When a wide needle is used, the procedure is called a core biopsy. When a thin needle is used, the procedure is called a fine-needle aspiration biopsy.

A procedure in which a sample of blood is examined to measure the amounts of certain substances made in the body. An abnormal amount of a substance can be a sign of disease in the organ or tissue that produces it.

The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.

The removal of a sample of tissue from the bone marrow with a needle for examination under a microscope.

A drug used to treat multiple myeloma that has gotten worse during treatment with other anticancer drugs. It is also used to treat mantle cell lymphoma in patients who have already received at least one other type of treatment. Bortezomib is also being studied in the treatment of other types of cancer. It is a type of proteasome inhibitor and a type of dipeptidyl boronic acid. Also called PS-341 and Velcade.

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Treatment with drugs that kill cancer cells.

The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER (1-800-422-6237), or by using the LiveHelp instant-messaging service at https://cissecure.nci.nih.gov/livehelp/welcome.asp. Also called Cancer Information Service.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

A condition in which stool becomes hard, dry, and difficult to pass, and bowel movements don’t happen very often. Other symptoms may include painful bowel movements, and feeling bloated, uncomfortable, and sluggish.

A series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography scan, computerized axial tomography scan, and computerized tomography.

To heal or restore health; a treatment to restore health.

The process of identifying a disease, such as cancer, from its signs and symptoms.

In medicine, a disturbance of normal functioning of the mind or body. Disorders may be caused by genetic factors, disease, or trauma.

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

A condition marked by extreme tiredness and inability to function due lack of energy. Fatigue may be acute or chronic.

A method of measuring the number of cells in a sample, the percentage of live cells in a sample, and certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface. The cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The measurements are based on how the light-sensitive dye reacts to the light.

The active ingredient in a drug used to treat B-cell chronic lymphocytic leukemia (CLL) that has not responded to treatment with other anticancer drugs or that has gotten worse. Fludarabine blocks cells from making DNA and may kill cancer cells. It is a type of purine antagonist and a type of ribonucleotide reductase inhibitor.

Inherited; having to do with information that is passed from parents to offspring through genes in sperm and egg cells.

An intensive drug treatment to kill cancer cells, but that also destroys the bone marrow and can cause other severe side effects. High-dose chemotherapy is usually followed by bone marrow or stem cell transplantation to rebuild the bone marrow.

The complex group of organs and cells that defends the body against infections and other diseases.

A protein that acts as an antibody. Immunoglobulins are made by B cells and plasma cells. An immunoglobulin is a type of glycoprotein with two heavy chains and two light chains. Also called Ig.

The number of new cases of a disease diagnosed each year.

A type of cancer that grows slowly.

A device that concentrates light into an intense, narrow beam used to cut or destroy tissue. It is used in microsurgery, photodynamic therapy, and for a variety of diagnostic purposes.

An area of abnormal tissue. A lesion may be benign (noncancerous) or malignant (cancerous).

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Lymph nodes filter lymph (lymphatic fluid), and they store lymphocytes (white blood cells). They are located along lymphatic vessels. Also called lymph gland.

A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. A lymphocyte is a type of white blood cell.

Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop.

Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

An indolent (slow-growing) type of non-Hodgkin lymphoma marked by abnormal levels of IgM antibodies in the blood and an enlarged liver, spleen, or lymph nodes. Also called Waldenström macroglobulinemia.

A condition in which the blood contains high levels of large proteins and is too thick to flow through small blood vessels. One type is Waldenström macroglobulinemia, which is a type of cancer.

A diagnostic indication that disease may develop.

A statistics term. The middle value in a set of measurements.

A type of cancer that begins in plasma cells (white blood cells that produce antibodies). Also called Kahler disease, myelomatosis, and plasma cell myeloma.

NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. It conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://www.cancer.gov. Also called National Cancer Institute.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Neoplasms may be benign (not cancerous), or malignant (cancerous). Also called tumor.

A bundle of fibers that receives and sends messages between the body and the brain. The messages are sent by chemical and electrical changes in the cells that make up the nerves.

The study of cancer.

A doctor who identifies diseases by studying cells and tissues under a microscope.

PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.

The lower part of the abdomen, located between the hip bones.

A nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Peripheral neuropathy may be caused by physical injury, infection, toxic substances, disease (such as cancer, diabetes, kidney failure, or malnutrition), or drugs, including anticancer drugs. Also called neuropathy.

An exam of the body to check for general signs of disease.

The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma.

A type of immune cell that makes large amounts of a specific antibody. Plasma cells develop from B cells that have been activated. A plasma cell is a type of white blood cell. Also called plasmacyte.

The process of separating certain cells from the plasma in the blood by a machine; only the cells are returned to the person. Plasmapheresis can be used to remove excess antibodies from the blood.

A tiny piece of a cell found in the blood that breaks off from a large cell found in the bone marrow. Platelets help wounds heal and prevent bleeding by forming blood clots. Also called thrombocyte.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

A cell that carries oxygen to all parts of the body. Also called erythrocyte and RBC.

A monoclonal antibody used to treat certain types of B-cell non-Hodgkin lymphoma. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. Rituximab binds to the protein called CD20, which is found on B-cells. Also called Rituxan.

Having to do with the skeleton (bones of the body).

The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage.

An organ that is part of the lymphatic system. The spleen makes lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach.

An operation to remove the spleen.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with standard therapy. Also called best practice and standard of care.

A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

A set of symptoms or conditions that occur together and suggest the presence of a certain disease or an increased chance of developing the disease.

A drug that is used to treat multiple myeloma in patients who have just been diagnosed, and a painful skin disease related to leprosy. It is also being studied in the treatment of other types of cancer. Thalidomide belongs to the family of drugs called angiogenesis inhibitors. Also called Thalomid.

Treatment.

A group or layer of cells that work together to perform a specific function.

A surgical procedure in which tissue or an organ is transferred from one area of a person’s body to another area, or from one person (the donor) to another person (the recipient).

A substance that may be found in tumor tissue or released from a tumor into the blood or other body fluids. A high level of a tumor marker may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (in ovarian cancer), CA 15-3 (in breast cancer), CEA (in ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (in prostate cancer).

In medicine, a very simple microorganism that infects cells and may cause disease. Because viruses can multiply only inside infected cells, they are not considered to be alive.

Refers to a blood cell that does not contain hemoglobin. White blood cells include lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. These cells are made by bone marrow and help the body fight infections and other diseases. Also called leukocyte and WBC.

A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.