Reviewed by C.H. Weaver M.D., Medical Editor (8/2018)
Mantle cell lymphoma (MCL) is a lymphoproliferative disorder derived from a subset of naive pregerminal center cells localized in primary follicles or in the mantle region of secondary follicles. Mantle cell lymphoma (MCL) accounts for between 2% and 10% of all non-Hodgkin lymphomas.1 Mantle cell lymphoma involves the abnormal growth of immune cells known as B cells, and can affect lymph nodes, the spleen, blood, bone marrow, and other tissues.
Mantle cell lymphoma affects men more often than women and is most common in older adults; roughly half of people with MCL are over the age of 68 at the time of diagnosis and the majority are diagnoses with advanced diseasw.1 The causes of the condition are unknown.
Signs & Symptoms of Mantle Cell Lymphoma
Symptoms that may be caused by MCL or other types of non-Hodgkin lymphoma include the following:2
- Swollen, painless lymph nodes in the neck, armpits, or groin
- Unexplained weight loss
- Soaking night sweats
- Coughing, trouble breathing, or chest pain
- Weakness and tiredness that don’t go away
- Pain, swelling, or a feeling of fullness in the abdomen
Mantle cell lymphoma is considered an aggressive form of non-Hodgkin lymphoma, though outcomes can vary considerably among patients. Median overall survival is roughly 5 to 7 years.3
Diagnosis and Staging of Mantle Cell Lymphoma
If lymphoma is suspected, patients will usually have a biopsy performed. A biopsy involves the removal and examination of a sample of affected tissue. It allows a doctor to determine the presence and type of lymphoma. A diagnostic workup may also involve a physical exam, blood tests, and imaging scans.
If the biopsy confirms a diagnosis of mantle cell lymphoma, patients often undergo additional tests and imaging scans to determine the extent (stage) of the disease. Stage ranges from I to IV, with higher stages indicating more extensive disease. A majority of patients with MCL have Stage III or Stage IV disease at the time of diagnosis.2 Additional tests that are often performed may include:
- Bone marrow aspirate/biopsy
- Immunophenotyping helps differentiate MCL from other small B-cell lymphomas.
- Body CT scanning is important for initial staging and for assessing response to treatment.
- Blood studies
- Beta2-microglobulin: An elevated level indicates a poor prognosis
Immunophenotyping: MCL cells are monoclonal B cells with the following characteristics:
- CD5+ and pan B-cell antigen positive (eg, CD19, CD20, CD22).
- Lack expression of CD10 and CD23.
- Overexpress cyclin D1
Another tool that may be used to assess patients is the Mantle Cell International Prognostic Index (MIPI). The MIPI uses four pieces of information—age, performance status (ability to perform activities of daily living), lactate dehydrogenase levels, and leukocyte count—to classify MCL patients as low risk, intermediate risk, or high risk. Overall survival tends to be worse in higher-risk patients.4 Information about stage and MIPI result help guide treatment decisions.
Treatment of Advanced Mantle Cell Lymphoma
Most patients with MCL are diagnosed with an advanced stage of the disease. Some of these patients will have indolent (slow-growing) MCL that can be managed with close observation, but a majority of patients will require treatment.1
Although newer approaches to treatment have improved outcomes for people with MCL, most people will eventually experience a relapse. Given the limitations of standard treatments, people with MCL may wish to participate in a clinical trial. Clinical trials are studies that evaluate the effectiveness and safety of new cancer drugs or cancer treatment strategies. Good sources of information about ongoing clinical trials include the patient’s cancer treatment team and the website of the National Cancer Institute.
Standard initial drug therapy for MCL often involves a combination of chemotherapy drugs often combined with the precision cancer medicine Rituxan® (rituximab). Rituxan is a type of drug known as a monoclonal antibody that recognizes and targets a specific protein (CD20) found on the surface of B cells, including the cancerous B cells of MCL. The binding of Rituxan to the B cell prompts the immune system to destroy the cell and may also have direct anticancer effects on the cell.
Some of the drug combinations used to treat MCL are more intensive than others. Because more intensive treatments tend to have more side effects, they are often reserved for younger patients or patients in good overall health.
- Leukeran (chlorambucil)
- Cyclophosphamide, vincristine, and prednisone (CVP)
- Cyclophosphamide, doxorubicin vincristine, and prednisone (CHOP)
- Hyperfractionated cyclophosphamide, vincristine, (Adriamycin), and dexamethasone (hyper-CVAD)
- Velcade (bortezomib),cyclophosphamide, doxorubicin, and prednisone
- Revlimid (Lenalidomide)
- Imbruvica (Ibrutinib)
For patients who respond to initial treatment, additional treatment options include maintenance Rituxan (long-term Rituxan that is given to maintain the treatment response as long as possible) or high-dose chemotherapy followed by an autologous stem cell transplant. An autologous stem cell transplant uses the patient’s own blood stem cells—collected prior to treatment—to replace the stem cells that are destroyed during high-dose chemotherapy.
If the MCL does not respond to initial treatment or later returns, patients may be treated with a different drug combination than was used originally. An allogenic stem cell transplant (a stem cell transplant using donor stem cells) may also be an option.
For more information about stem cell transplantation, visit Stem Cell Transplantation Overview.
Treatment of Early-Stage MCL
Treatment of Stage I or Stage II MCL may involve radiation therapy, the types of drug therapies that are also used for advanced disease, or both radiation therapy and drug therapy. Because relatively few people are diagnosed with early-stage MCL, there is limited information available about which approach is most effective.
Strategies to Improve Treatment
Because outcomes remain suboptimal for many people with MCL, researchers continue to develop and test new approaches to treatment. These new approaches include vaccines as well as many different types of drugs. Zevalin® (ibritumomab tiuxetan), for example, is a radioimmunotherapeutic. Radioimmunotherapy involves treatment with a radioactive substance linked to a monoclonal antibody. In the case of Zevalin, the antibody recognizes and binds to the CD20 protein found on the surface of B cells. The binding of the antibody delivers the radiation directly to the cancer. Zevalin has been approved for the treatment of patients with certain other types of non-Hodgkin lymphoma, and it is also producing promising results in studies of patients with MCL.5
Patients who are interested in participating in a clinical trial of new treatment approaches may wish to discuss the risks and benefits with their physician. Information about ongoing clinical trials is also available from the National Cancer Institute.
1 Shah BD, Martin P, Sotomayor EM. Mantle cell lymphoma: a clinically heterogeneous disease in need of tailored approaches. Cancer Control. 2012;19:227-235.
2 National Cancer Institute. What You Need to Know About™ Non-Hodgkin Lymphoma. 2008.
3 Leukemia and Lymphoma Society. Mantle Cell Lymphoma Facts. July 2012.
4 Vose JM. Mantle cell lymphoma: 2012 update on diagnosis, risk-stratification, and clinical management. American Journal of Hematology. 2012;87:605-609.
5 Smith MR, Li H, Gordon L et al. Phase II Study of Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Immunochemotherapy Followed by Yttrium-90–Ibritumomab Tiuxetan in Untreated Mantle-Cell Lymphoma: Eastern Cooperative Oncology Group Study E1499. Journal of Clinical Oncology. 2012;30:3119-3126.