An Overview of Mantle Cell Lymphoma

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A doctor talks to a patient. Thomas Barwick/Getty Images

Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin’s lymphoma that arises in the B-lymphocytes, a type of white blood cell that helps fight infection. MCL usually affects lymph nodes and can also involve other organs. Most people with MCL have an aggressive form of the disease that requires prompt treatment. Candidates for intensive therapy can achieve remissions lasting up to 7 to 10 years, or even longer. There are a growing number of treatment options for both newly diagnosed and relapsed MCL. A small group of people have a much more indolent form of MCL that may not require immediate treatment and may be stable for years.

Symptoms

Symptoms of MCL are similar to those of many other types of non-Hodgkin’s lymphoma and may include one or more of the following:

  • Painless, swollen lymph nodes
  • Fevers and night sweats
  • Unintentional weight loss
  • Diarrhea, nausea/vomiting, abdominal pain or discomfort

The most common symptom of MCL is one or more painless, swollen lymph nodes. Night sweats, fevers, and unintentional weight loss are also possible, with up to one-third of diagnosed patients having such symptoms.

Enlarged lymph nodes may be close enough beneath the skin’s surface so that they can be felt with the hands. However, they may be deeper inside the body. Less commonly, MCL develops outside of the lymph nodes, in which case the most common site is the gastrointestinal tract. When MCL affect the stomach or bowel, it may produce symptoms such as diarrhea and abdominal pain.

In forms of MCL that are less aggressive, people often have no lymph node enlargement and instead have an enlarged spleen. This can either produce no symptoms or can cause the feeling of fullness or pain in the left upper abdomen that may spread to the left shoulder. This feeling of fullness may be somewhat constant, or it may be noticed after eating just a small amount of food. Another term for an enlarged spleen is splenomegaly.

Causes

Like many forms of cancer, the exact underlying cause of MCL is unknown, but researchers suspect that certain genetic and environmental factors may be important. MCL mostly affects older adults, and it is common for individuals diagnosed with MCL to be in their late 50s or early-to-mid 60s. Men are affected more often than women, but the reasons for this pattern are unknown.

Malignancies develop in association with changes in genetic code, or mutations in DNA. Most people with MCL have acquired a specific genetic abnormality in which there has been an exchange of genetic material between two chromosomes: chromosome 11 and 14. This exchange is called a chromosomal translocation, and this particular translocation is written scientifically as t(11;14)(q13;q32). When this translocation occurs in B-lymphocytes, it may contribute to the development of MCL as well as other B-cell malignancies.

Other clues about causes may relate to where the MCL cells originate. The "mantle" in MCL originally referred to the location of cells once thought to be primarily involved in the malignancy. MCL seemed to develop from a part of the lymph node called the mantle zone, an area of cells that surround and envelop another structure, the germinal center. 

Diagnosis

The diagnosis of MCL, like other types of lymphoma, often depends on clues that are revealed in the process of a thorough clinical evaluation. Certain symptoms and physical findings may be detected, and a variety of specialized tests are used to confirm the specific type and subtype of non-Hodgkin (NHL), to determine the extent of the disease, and to help define the most appropriate treatments.

In the physical examination, the doctor may feel the lymph nodes in certain areas to detect any swelling. The exam also includes touching the abdomen under the rib cage area to try to detect swollen organs (liver, spleen) and abnormal fluid accumulation that may be associated with disease of the lymphatic system.

Blood tests, biopsies, imaging tests, bone marrow examination, cerebrospinal fluid (CSF) analysis, and/or other tests are all possible as part of the workup for lymphoma.

Biopsy

A sample of the involved tissue, or a biopsy, is taken to study its microscopic appearance and to perform various tests on the suspicious cell. Often lymph nodes are biopsied, or in some instances, an entire enlarged lymph node that is suspected of being cancerous will be removed and studied. In some cases, the suspicious sites may not be easily accessible from the outside, and laparoscopy or laparotomy surgery may be necessary to get samples that are deep in the abdomen or pelvis.

Using the biopsy tissue, specialized tests are done to help determine the malignancy's specific cell type of origin. MCL is a B-cell lymphoma, and MCL cells produce distinctive proteins (CD5, CD19, CD20, and CD22). Other studies are often done to detect the presence of the chromosome 11;14 translocation in malignant lymphocytes and the cyclin D1 protein. Still, other studies, such as testing for the presence of TP53 mutation, may have implications for deciding on the best treatment.

Imaging

Any number of imaging studies may be needed, including x-ray imaging, computed tomography (CT) scanning, magnetic resonance imaging (MRI), gallium scans, and/or other studies. CT scans may be performed to look in areas such as the neck, chest, abdomen, and pelvis to help detect enlargement of certain lymph nodes disease that has spread to certain organs. MRI may be used to detect any disease involvement of the brain and spinal cord. Other forms of imaging, such as gallium scanning and FDG-PET may provide important information about the disease and its extent.

Bone Marrow Examination

A bone marrow examination actually consists of two separate but usually concurrent tests: a bone marrow aspiration to retrieve the liquid portion of the bone marrow and a bone marrow biopsy for the solid portion. Tests on the blood cells obtained from bone marrow can help determine whether MCL involves the bone marrow at all.

Cerebrospinal Fluid Analysis

Sometimes, an analysis of cerebrospinal fluid is recommended to look for abnormalities that would indicate the spread of cancer to the brain and spinal cord. This fluid is obtained for analysis by a procedure known as a lumbar puncture.

Part of the workup for MCL is establishing the diagnosis, but the other part is to try to get as much information as possible about the risk from this disease. A small percentage of MCL cases are more indolent; others behave more aggressively. It is common for MCL to have spread beyond lymph nodes to affect the spleen, the bone marrow, and organs outside the lymphatic system, such as the liver or regions of the digestive (gastrointestinal [GI]) tract at the time of diagnosis.

In determining the stage of MCL and in looking ahead to treatment, a whole host of information is compiled to predict the potential disease course and consider appropriate treatment options. Your age and general health, tumor size, levels of the enzyme lactate dehydrogenase, and other factors can inform the treatment decision.

Other tests may be done in anticipation of treatment; for example, there may be tests of the heart and lungs in advance of intensive treatment to make sure such treatment would be advisable.

Treatment

There are a number of different treatment options available for patients newly diagnosed with MCL. The right ones for you will depend on your disease, your goals, and your individual circumstances. Often treatment regimens are categorized as aggressive therapy or less aggressive therapy.

First-Line Treatment

Examples of aggressive treatment include the following for induction of remission:

  • RDHA (rituximab, dexamethasone, cytarabine) + platinum (carboplatin, cisplatin, or oxaliplatin)
  • Alternating RCHOP/RDHAP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)/(rituximab, dexamethasone, cytarabine, cisplatin)
  • The NORDIC regimen (dose-intensified induction immunochemotherapy with rituximab + cyclophosphamide, vincristine, doxorubicin, prednisone [maxi-CHOP]) alternating with rituximab + high-dose cytarabine)

Young patients with MCL would typically receive aggressive, intensive chemotherapy with high-dose cytarabine and then a stem cell transplant. Allogeneic stem cell transplantation is an option at first remission or at the time of relapse.

Less aggressive first-line treatment examples may include:

  • Bendamustine + rituximab
  • VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone)
  • RCHOP

Maintenance therapy may follow the first line regimen. Rituximab every eight weeks is one such regimen for which the benefits are currently being evaluated.

If the analysis of the malignancy shows that certain mutations are present, such as TP53 mutations, clinicians tend to steer away from aggressive chemotherapy in favor of less aggressive or more investigational approaches, like clinical trials.

Second-Line Treatment

Whether after seven years of remission or after just three years following a less aggressive initial treatment, there are many options for second-line treatment. Researchers are still trying to sort out which ones may be the best to start with, and how best to sequence them. Examples include:

  • Acalabrutinib
  • Ibrutinib ± rituximab
  • Lenalidomide ± rituximab
  • Venetoclax
  • Bendamustine ± rituximab (if not previously given)
  • Bortezomib ± rituximab

The choice of second-line treatment depends on factors such as which regimen was given first-line, how long the remission lasted with that initial treatment, individual characteristics of the person with MCL (age, overall health, other medical conditions) and characteristics of the person’s MCL (higher risk vs lower risk), as well as personal preferences and insurance status /economic concerns.

A Word From Verywell

One of the most important things to keep in mind about MCL is that your MCL is not the same as someone else’s MCL, and that you are not a statistic. That is, different people have very different experiences with this disease.

 Some forms of MCL, such as the blastoid variant, are extremely aggressive and treated as such. Other forms behave more like chronic lymphocytic leukemia, a blood cancer that most people “die with, rather than die from.” Unfortunately, the latter group has been more of the exception rather than the rule for MCL. However, advances in treating the more common B-cell lymphomas are emerging at a record pace, and it is likely people with MCL will also benefit from these breakthroughs.

 

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Article Sources

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  • Mareckova A, Malcikova J, Tom N, et al. ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients. Leuk Lymphoma. 2019 Jan 10:1-9. doi: 10.1080/10428194.2018.1542144. [Epub ahead of print]

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