Mantle cell lymphoma

Definition

Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin's lymphoma characterized under the microscope by expansion of the mantle zone area of the lymph node with a homogeneous (structurally similar) population of malignant small lymphoid cells. These cancerous cells have slightly irregular nuclei and very little cytoplasm, and are mixed with newly made normal lymphocytes (white blood cells) that travel from the bone marrow to the lymph nodes and spleen. Unlike normal lymphocytes, they do not mature properly and become cancerous instead.

Description

The body's immune system produces two types of lymphocytes or white blood cells: the B cells which are made in the bone marrow and the T cells which are made in the thymus. Both types of cells are found in the lymph, the clear liquid that bathes tissues and circulates in the lymphatic system. Lymphomas are cancers that occur in this lymphatic system and B-Cell lymphomas—also called non-Hodgkin's lymphomas—include follicular lymphomas, small non-cleaved cell lymphomas (Burkitt's lymphoma ), marginal zone lymphomas (MALT lymphomas), small lymphocytic lymphomas, large cell lymphomas and also mantle cell lymphomas.

Mantle cell lymphoma accounts for 5% to 10% of all lymphomas diagnosed and 5% of B-cell lymphomas. There are three subsets of MCL cells: the mantle zone type, the nodular type, and the blastic or blastoid type. These various types often occur together to some degree, and approximately 30% to 40% of diagnoses are of mixed mantle and nodular type. As MCL develops further, the non-cancerous mantle centers also become invaded by cancerous cells. In about 20% of these cases, the cells become larger, and of the blastic (immature) type.

Extensive debates are ongoing concerning the grade of this cancer. European classification used to classify it as a low-grade cancer because it is initially slow-growing, while American classification considered it intermediate based on patients' shorter average survival rate. The combined European-American classification (REAL), is still discussing the status of mantle cell lymphoma. This is due to the mixed nature of MCL cells. Blastic type-MCL seems to be considered as a high-grade cancer because it spreads at about the rate of other lymphomas belonging to that category. The studies currently attempting to describe the precise nature of these cells will be key to any general agreement that is finally reached.

Demographics

Mantle cell lymphoma is rare in persons under the age of 50. It is most often seen in men aged 50-70 years. Out of 1, 000 persons diagnosed with MCL, approximately 33% will be women. This cancer has the shortest average survival of all lymphoma types.

Causes and symptoms

The cause of MCL is unknown. Many of its symptoms are shared by other lymphomas as well and patients generally complain of fatigue , anemia , low grade fevers, night sweats , weight loss , rashes, digestive disturbances, chronic sinus irritation, recurrent infections, sore throat, shortness of breath, muscle and bone aches and edema.

More specific symptoms include spleen enlargement (in about 60% to 80% of cases), particularly with nodular-type MCL. Swollen lymph nodes are an early-stage symptom, even though the general health of the patient is good. Mild anemia is also common. Some patients also report lower back pain, and burning pain in the legs and testicles. As MCL becomes more advanced, the lymph nodes increase in volume, and the general symptoms become more pronounced.

In the end stage of MCL, neurologic symptoms appear, indicating that the MCL has spread to the central nervous system.

Diagnosis

MCL is very similar to several other lymphoma types and special care must be taken with the diagnosis. It should not be made from blood or bone marrow specimens alone. It is believed that immunologic tests are required to make the correct diagnosis. Immunopheno-typing is one such test, it is used to determine what kind of surface molecules are present on cells, and thus, the exact type of lymphoma from a tissue sample. The Lymphoma Research Foundation of America recommends that several opinions be sought from recognized mantle cell experts to confirm the accuracy of the diagnosis.

At the time of diagnosis, mantle cell lymphoma has usually spread into other tissues such as the lymph nodes, spleen, bone marrow (up to 90% of cases), or to Waldeyer's ring (the ring of adenoid, palatine and lingual tonsils at the back of the mouth) or to the gastrointestinal tract. MCL can also spread to the colon, in which case it is diagnosed as multiple lymphomatous polyposis.

Treatment team

Depending on the type of MCL and stage of the cancer, the treatment team may include a radiation oncologist, a medical oncologist, a surgeon and a neurologist.

Clinical staging, treatments, and prognosis

There is no formal staging system for mantle cell lymphoma and no standard treatment has yet been adopted for MCL patients. Patients have been treated with surgery, radiation, single drug or combination chemotherapy and stem cell transplants. CHOP is one of the most common chemotherapy regimens for treating MCL. It derives its name from the combination of drugs used: Cyclophosphamide (cytoxan, neosar), adriamycin (doxorubicin or Hydroxydoxorubicin), vincristine (Oncovin), and Prednisone.

There is no cure for mantle cell lymphoma. As with other slow-growing lymphomas, spontaneous remissions have been reported, but only partial, lasting a year at the most. All mantle cell lymphoma experts agree that the long-term prognosis of MCL patients receiving conventional treatment is poor, and that there is an urgent need for new, improved therapies.

Alternative and complementary therapies

Because MCL is a cancer of the lymphatic system, immunologic therapies are often used, or combined with the more conventional radiation and chemotherapy treatments. Immunological therapies take advantage of the body's immune system. The immune system is a network of specialized cells and organs that defends the body against foreign invaders (antigens) by producing special "defense" proteins, an example of which are the antibodies. These substances recognize and attach to the antigens, usually found on the surface of cells and destroy them. There are reports of immunological therapies being used for MCL using interferon, one such natural substance produced by the body in response to a virus. Numerous studies show that interferons can stimulate the immune system to fight the growth of cancer, but there has not yet been enough evidence produced to see it emerge as a strong candidate for MCL treatment.

Other immunological therapies based on monoclonal antibodies (MABs or MOABs) have recently emerged, such as Rituxan (rituximab ). MABs work on cancer cells in the same way natural antibodies work, by identifying and binding to the target cells, alerting other cells in the immune system to the presence of the cancer cells. MABs are very specific for a particular antigen, meaning that one designed for a B-cell lymphoma will not work on T-cell lymphomas. MABs used alone may enhance a patient's immune response to the cancer but they are thought to be more efficient when combined to another form of therapy, such as a chemotherapeutic drug. This way, the cancer is attacked on two fronts: chemical attack from the chemotherapy and immune response attack stimulated by the MAB.

Coping with cancer treatment

It is important to have a caregiver system when receiving medical treatment for MCL, and it is just as important to have a network of support for coping with the non-medical aspects of the cancer. Friends, relatives, coworkers and health professionals all can provide help, as well as the national cancer associations, some specifically addressing the needs of lymphoma patients. Please refer to the Resources section at the end of this entry for contact information.

Clinical trials

Clinical trials addressing the needs of MCL patients are very recent because the mantle cell lymphoma subtype has only recently been defined. There are now several trials being carried out in the United States specifically for mantle cell. Some other trials designed for patients with lymphomas may also accept mantle cell patients. Ongoing trials in this area are cheifly concerned with investigating monoclonal antibodies. Information regarding clinical trials can be obtained through the Clinical Trials web site listed at the end of this entry.

The following clinical protocols are specifically designed for MCL patients:

• The MD Anderson Protocol (high-dose chemotherapy with or without stem cell transplant)
• Rituxan, by itself or with CHOP
• Bexxar
• Oncolym
• Flavopiridol
• Phenylacetate

Prevention

Because the cause of MCL is unknown, no prevention measures can be recommended.

Special concerns

Special concerns that apply to lymphoma patients may also apply to MCL patients. Because MCL is a cancer that usually involves chemotherapy and radiation therapy , it can be severely damaging to organ function and long-term resistance. In addition to the immediate side effects of these treatments, other effects appear after treatment is completed, one of which, called Post-Cancer Fatigue (PCF), is often seen with lymphoma patients. This is fatigue that persists after treatment and can sometimes be extreme. The medical team will be able to offer the best advice to deal with PCF.

See Also Acute lymphocytic leukemia; Central nervous system lymphomas

Resources

BOOKS

Cabanillas, F. Advances in Lymphoma Research. New York:Kluwer Academic Publishers, 1998.

Cannellos, G. P., T. A. Lister, J. L. Sklar, and R. Lampert, eds. The Lymphomas. St. Louis: W. B. Saunders Co., 1998.

Magrath, T., ed. The Non-Hodgkin's Lymphomas. London: E.Arnold, 1997.

PERIODICALS

Argatoff, L., J. Connors, R. Klasa, D. Horsman, R. Gascoyne."Mantle Cell Lymphoma: A Clinicopathologic Study of80 Cases." Blood 89 (1997):2067-78.

Grosfeld, J. L. "Risk-based Management of Solid Tumors in Children." In American Journal of Surgery 180 (November 2000): 322-7

Majlis, A., W. Pugh, M. Rodriguez, W. Benedict, and F. Cabanillas. "Mantle Cell Lymphoma: Correlation of Clinical Outcome and Biologic Features with Three HistologicVariants." In Journal of Clinical Oncology 15 (1997):1664-71.

Meusers, P., J. Hense, and G. Brittinger. "Mantle Cell Lymphoma: Diagnostic Criteria, Clinical Aspects and Therapeutic Problems." In Leukemia 11 (1997) Suppl. 2:S60-4.

ORGANIZATIONS

The Lymphoma Research Foundation of America 8800 Venice Blvd., Suite 207, Los Angeles, CA 90034. (310) 204-7040. <http://www.lymphoma.org> 5 July 2001.

The Leukemia and Lymphoma Society 1311 Mamaroneck Ave. White Plains, N.Y., 10605. (914) 949-5213. <http://l3.leukemia-lymphoma.org/hm_lls> 5 July 2001.

OTHER

Lymphoma Information Network Website. 7 June 2001. 5 July 2001 <http://www.lymphomainfo.net/nhl/types/mantle.html>.

Oregon Health and Science University, Cliniweb International Page on B-cell Lymphomas. 5 July 2001 <http://www.ohsu.edu/cliniweb/C15/C15.604.515.569.480.150.html>.

National Institutes of Health Clinical Trials 5 July 2001 <http://www.clinicaltrials.gov/>

Monique Laberge, Ph.D.

QUESTIONS TO ASK THE DOCTOR

• How advanced is my lymphoma?
• Do you know of any clinical trials in which I may participate?
• Has this center had much experience with MCL cases?
• What are the choices for treatment and what do you recommend?
• Should I obtain a second opinion?
• What are the possible short-term and long-term side effects of the treatment and what can be done about them?
• Are there other risks from the treatment?
• What are the chances of success?
• Are there complementary or alternative therapies that may be helpful?
• Are there support groups in the area that can help me cope with this disease?

KEY TERMS

Anemia

—A condition caused by a reduction in the amount of red blood cells produced by the bone marrow. Its symptoms are general weakness and lack of energy, dizziness, shortness of breath, headaches, and irritability.

Antibody

—A protein (immunoglobulin) produced by plasma cells (mature B cells) to fight infections in the body. They are released into the circulatory system in response to specific antigens and thus target those antigens that induced their production.

Antigen

—An antigen is any substance which elicits an antibody response. As such, they are substances that stimulate a specific immune response of the body and are capable of reacting with the products of that response. Antigens may be foreign chemical substances or proteins located on the surface of viruses, bacteria, toxins, tumors and other infectious agents.

B-Cell lymphocyte

—A type of lymphocyte (white blood cell). B cells react to the presence of antigens by dividing and maturing into plasma cells.

B-cell lymphomas

—Non-Hodgkin's lymphomas that arise from B cells.

Blood cell

—Cellular component of blood. There are three general types: white blood cells, red blood cells, and platelets, all which are produced in the bone marrow.

Cytoplasm

—The organized complex of organic and inorganic substances external to the nuclear membrane of a cell.

DNA

—Deoxyribonucleic acid are nucleic acids that are the part of the cell nucleus that contains and controls all genetic information.

Edema

—Swelling of a body part caused by an abnormal buildup of fluids.

Gene

—The specific site on a chromosome, consisting of protein and DNA responsible for the transmittal and determination of hereditary characteristics.

Gene therapy

—The use of genes to treat cancer and other diseases.

Immune system

—The system within the body, consisting of many organs and cells, that recognizes and fights foreign cells and disease.

Lymph

—A milky white liquid responsible for carrying the lymphocytes in the lymphatic vessels.

Lymphatic system

—Tissues and organs such as the bone marrow, spleen, thymus and lymph nodes that produce and store cells to fight infection and disease. Also includes the lymphatic vessels that carry lymph.

Lymphoma

—Cancers that starts in the lymphatic system. Lymphomas are classified into two categories—Hodgkin's Disease and the non-Hodgkin's lymphomas.

Lymphocyte

—A type of white blood cell that defends the body against infection and disease. Lymphocytes are found in the bloodstream, the lymphatic system, and lymphoid organs. The two main types of lymphocytes are the B cells (produced in the bone marrow) and the T cells (produced in the thymus).

Monoclonal antibody

—An antibody raised against a specific antigen. Monoclonal antibodies are being used to target chemotherapy or radioactive substances directly to cancer cells.

Non-Hodgkin's lymphomas

—Lymphomas characterized by different types of cancerous lymphatic cells, excluding those characterized by Hodgkin's disease.

Remission

—A complete or partial disappearance of the signs and symptoms of cancer, usually in response to treatment.

Stem cell

—Primitive cell found in the bone marrow and in the blood stream. Stem cells become different types of mature blood cells, thus enabling them to rejuvenate the circulatory and immune systems.

Stem cell transplant

—Treatment procedure by which young blood stem cells are collected from the patient (autologous) or another matched donor (allogeneic). High-dose chemotherapy and/or radiation is given, and the stem cells are reinserted into the patient to rebuild their immune system.