Mantle Cell Lymphoma

Mantle cell lymphoma is a rare type of blood cancer that develops when certain white blood cells grow out of control. While it cannot be cured, treatment can help manage symptoms and extend periods when the disease is not active.

Table of contents

• What is mantle cell lymphoma?
• Types of mantle cell lymphoma
• What causes this condition?
• Who is affected?
• Signs and symptoms
• How is it diagnosed?
• Treatment approaches
• What to expect
• Living with mantle cell lymphoma

What is mantle cell lymphoma?

Mantle cell lymphoma is a rare type of blood cancer that starts in your lymphocytes, which are white blood cells that help fight infections^[1]. It is a subtype of non-Hodgkin lymphoma, which is cancer that affects the lymphatic system^[2].

The lymphatic system is an important part of your immune system. It includes organs, glands, tubelike vessels, and clusters of cells called lymph nodes. These nodes are located throughout your body, including your neck, armpits, and groin^[1].

Mantle cell lymphoma gets its name from where the cancer begins. It starts inside an area called the mantle zone of a lymph node. The mantle zone is a ring of cells surrounding the inner part of the lymph node. These cells are white blood cells called B lymphocytes^[1].

In mantle cell lymphoma, changes happen that turn the B lymphocytes into cancer cells. These cancer cells build up in the lymph nodes and can spread to other parts of the body, including the blood, bone marrow, spleen, liver, and digestive system^[1][2].

Mantle cell lymphoma accounts for roughly six percent of all non-Hodgkin lymphoma cases in the United States, with about 4,000 new cases each year^[3][11]. It affects about 1 in 200,000 people^[2][4].

Types of mantle cell lymphoma

There are two main types of mantle cell lymphoma^[1][2]:

• Classic mantle cell lymphoma (also known as nodal mantle cell lymphoma or aggressive mantle cell lymphoma): This is the most common type. It typically starts in the lymph nodes but usually spreads to other areas of your body. It is usually more aggressive, meaning it grows and spreads more quickly. Most cases of mantle cell lymphoma are this type.
• Leukemic non-nodal mantle cell lymphoma (also known as indolent mantle cell lymphoma): This type usually causes a swollen spleen and lymphoma cells in your blood and bone marrow. It tends to grow more slowly than the classic type. About 20 percent of patients have this indolent form^[11].

What causes this condition?

Most of the time, mantle cell lymphoma happens when certain genes change (or mutate) and alter how your B cells function^[2]. Researchers don’t know what triggers this genetic change, but they understand how it works.

Mantle cell lymphoma is characterized by a specific change in chromosomes called a translocation. In more than 95 percent of cases, there is a translocation between chromosomes 11 and 14, written as t(11;14)(q13;q32)^[4][11]. This results in overexpression of a gene called cyclin D1 (also known as CCND1).

Here’s how the process unfolds^[2]:

• Abnormal B cells make too much cyclin D1, which is a protein that helps B cells grow
• The cyclin D1 overload makes B cells duplicate and multiply uncontrollably
• The duplicate cells make tumors

Mantle cell lymphoma is typically sporadic, meaning it occurs by chance, though it may have a higher incidence in some families^[4]. You cannot “catch” it from others like you would catch a cold^[9].

Who is affected?

Mantle cell lymphoma can affect anyone, but certain groups have a higher risk. Men get mantle cell lymphoma more often than women, with a male-to-female ratio of about 3 to 1^[4][15]. People between the ages of 60 and 70 have a slightly higher risk^[2]. The median age at diagnosis ranges from 60 to 70 years old, though the age range at presentation can be anywhere from 35 to 85 years^[4][15].

Signs and symptoms

Mantle cell lymphoma can be difficult to detect early, as symptoms often resemble other illnesses^[3]. They may not always appear to be cancer-related. That’s one reason why mantle cell lymphoma is usually in the later stages at the time of diagnosis^[2]. Many cases are diagnosed after routine blood work or imaging^[3].

You might not have any symptoms with mantle cell lymphoma. But if you do, they might include^[2][3][9]:

• Swollen lymph nodes in your neck, armpits, or groin (these swellings are usually painless)
• Fatigue or weakness
• Unexplained weight loss
• Night sweats or fever
• Loss of appetite
• Abdominal pain or bloating
• Indigestion
• Changes in bowel habits
• A sense of fullness or discomfort from enlarged tonsils, liver, or spleen
• Bruising
• Headaches
• Nausea or vomiting

Some patients experience what doctors call “B symptoms,” which include heavy sweating at night, high temperatures that come and go with no obvious cause, and losing a lot of weight (more than one tenth of your total weight)^[5]. About 40 percent of patients have B symptoms at diagnosis^[15].

Most patients with mantle cell lymphoma have stage III or IV disease at diagnosis, meaning the cancer has spread throughout the body^[11]. Frequently, the disease is diagnosed once it has spread throughout the body, involving the lymph nodes, but it can also affect the bone marrow and gastrointestinal tract^[3].

How is it diagnosed?

Healthcare providers usually suspect mantle cell lymphoma after routine blood work shows a high lymphocyte count^[2]. Diagnosis often begins with a physical exam that checks for swollen lymph nodes in the neck, underarms, and groin. The exam also checks for a swollen spleen or liver^[12].

Your healthcare provider may use many different tests to diagnose mantle cell lymphoma^[2][12]:

Blood tests

Blood tests can sometimes show if lymphoma cells are present. Your doctor takes some of your blood and sends it to a lab to be analyzed. The blood tests can reveal the number of blood cells you have, how well your kidneys and liver are working, and whether you have certain proteins in the blood that suggest you have mantle cell lymphoma^[9]. Tests may include a complete blood count (CBC), comprehensive metabolic panel (CMP), lactate dehydrogenase (LDH) test, or a uric acid level test^[2].

One-quarter to one-half of patients with mantle cell lymphoma also have higher-than-normal levels of certain proteins that circulate in the blood, such as lactate dehydrogenase (LDH) and beta-2 microglobulin^[3].

Biopsy

Your healthcare professional may suggest a lymph node biopsy to look for cancer cells. A biopsy is a procedure to remove a sample of tissue for testing in a lab. A lymph node biopsy involves removing all or part of a lymph node^[12]. The lymph nodes in your neck, armpits, and groin are close to your skin. Your doctor will numb your skin, then make a small cut and remove a sample of the lymph node^[9].

Your healthcare provider may also recommend a bone marrow biopsy. These procedures can help confirm the presence of cancer cells. Once a provider takes a tissue sample, they’ll send it to a pathologist for testing^[2].

Laboratory testing of cells

Lymphoma cells collected from a lymph node biopsy or bone marrow biopsy go to a lab for testing. In the lab, tests may show whether you have mantle cell lymphoma^[12]. Identification of excess cyclin D1 from a biopsy is considered a very sensitive tool for diagnosing mantle cell lymphoma. Overproduction of cyclin D1 protein in the lymphoma cells is found in more than 90 percent of patients^[3].

Immunophenotyping helps differentiate mantle cell lymphoma from other small B-cell lymphomas. On immunophenotyping, tumor cells in mantle cell lymphoma are single-type B cells that express surface immunoglobulin, are characteristically CD5-positive and pan B-cell antigen positive (such as CD19, CD20, CD22), lack expression of CD10 and CD23, and overexpress cyclin D1^[15].

Imaging tests

Your provider might take imaging tests to determine how far the cancer has spread^[2]. Imaging tests make pictures of the body and can show the location and extent of mantle cell lymphoma. Tests might include CT scans (computed tomography) and PET scans (positron emission tomography)^[12]. Depending on the location of the cancer, you might need a colonoscopy, EGD (esophagogastroduodenoscopy), or other procedures^[2].

You might have an endoscopy if your doctor thinks lymphoma might be affecting your digestive system. This is when the doctor passes a thin tube through your mouth or your back passage. They can look at your digestive system and take biopsies of any abnormal looking tissue^[5].

Treatment approaches

There’s no cure for mantle cell lymphoma, but treatment can manage your symptoms^[2]. While mantle cell lymphoma often can’t be cured, treatments can shrink the cancer size and help contain it. Treatment may increase the time that the cancer stays away, known as remission, and help prolong life^[1].

The type of treatment selected depends on multiple factors, including the stage of disease, the age of the patient, and the patient’s overall health^[10]. Treatment for mantle cell lymphoma may include radiation therapy, immunotherapy, chemotherapy, targeted therapy, CAR-T cell therapy, and bone marrow transplant (also called a bone marrow stem cell transplant)^[1].

Active surveillance (watch and wait)

For the subset of patients who do not yet have symptoms and who have a relatively small amount of slow-growing disease, “active surveillance” (also known as “watch and wait” and “watchful waiting”) may be an acceptable option^[10]. With this strategy, patients’ overall health and disease are monitored through regular checkup visits and various evaluating procedures, such as laboratory and imaging tests. Active treatment is started if the patient begins to develop lymphoma-related symptoms or there are signs that the disease is progressing^[10].

Chemotherapy and immunotherapy

Initial treatment approaches for aggressive mantle cell lymphoma in younger patients include combination chemotherapy, typically in combination with the monoclonal antibody rituximab (Rituxan), as first-line treatment^[10]. Chemotherapeutic treatment approaches used to treat mantle cell lymphoma include^[10]:

• R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
• Bendamustine (Treanda) in combination with rituximab
• Hyper-CVAD (cyclophosphamide, doxorubicin, vincristine, dexamethasone alternating with high-dose methotrexate and cytarabine) plus rituximab

For older or less fit patients, less intensive chemotherapy followed by a prolonged course of rituximab alone, known as maintenance therapy, is often recommended^[10].

Stem cell transplantation

Consolidation high-dose chemotherapy followed by autologous stem cell transplantation (in which patients receive their own stem cells) is often utilized to prolong remission in younger, medically fit patients^[10].

Targeted therapies

Several targeted therapies have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of mantle cell lymphoma^[3]:

• BTK inhibitors (Bruton kinase inhibitors): These include ibrutinib, acalabrutinib, and zanubrutinib
• Proteasome inhibitors: Bortezomib (Velcade) has been approved for the treatment of mantle cell lymphoma patients^[10]
• Immunomodulatory agents: Lenalidomide has been approved as a targeted therapy

CAR-T cell therapy

CAR-T cell therapy (chimeric antigen receptor T-cell therapy) is a newer treatment option that has opened a new venue for treating mantle cell lymphoma^[13]. Treatment for mantle cell lymphoma may include this approach^[1].

Clinical trials

Participation in clinical trials may offer access to the latest treatments and innovations^[3]. With advances in pharmacokinetic analysis and drug discovery, treatment strategy has evolved from chemotherapy to combination of targeted, epigenetic, and immune therapies^[13].

What to expect

With mantle cell lymphoma, you might have periods of remission followed by periods of recurrence. That means the cancer can go away and come back, often several times^[2]. People with mantle cell lymphoma often experience a cycle of remission and relapse^[2].

Mantle cell lymphoma is highly responsive to treatment, but not curable in most cases^[11]. Treatment can’t cure mantle cell lymphoma, but it can lengthen the amount of time you’re in remission^[2].

The outlook varies depending on the type of mantle cell lymphoma. Patients with the indolent (slow-growing) version have a significantly better prognosis, with a median survival exceeding 15 years. Many of these patients can defer therapy on initial presentation and be followed with a watchful waiting approach^[11].

Most patients with mantle cell lymphoma (80 percent) present with more aggressive disease. These patients have a median survival exceeding 8 to 10 years^[11].

Measuring certain proteins can help physicians determine how aggressive an individual patient’s mantle cell lymphoma is and may guide therapy decisions^[3]. Several prognostic systems are used, including the Mantle Cell Lymphoma International Prognostic Index (MIPI), ki-67 proliferation index, and TP53 mutation status^[13].

Potential complications

As mantle cell lymphoma progresses, you might develop complications like^[2]:

• Gastrointestinal bleeding
• Ruptured spleen
• Tumor lysis syndrome

Living with mantle cell lymphoma

Whether you have just been diagnosed, are having treatment, or are in remission, living with mantle cell lymphoma can be challenging. It’s normal if you are finding it hard, both physically and emotionally^[18].

Learning about your condition can help you make decisions and feel more in control, but it’s important to take things at your own pace and ask questions when you are ready^[18]. Even if you have few symptoms and feel generally well, getting a diagnosis can be challenging^[18].

Getting support

Support from others can help you deal with your challenges and feel more like your normal self^[25]. Support can come in many forms:

• A friend who comforts you
• Family members who pitch in with household chores
• A mental health professional who helps you come to terms with your diagnosis
• Financial aid that covers some of your bills^[25]

Opening up to those you trust strengthens your relationships and helps you sort out the emotions you’re dealing with^[25]. When people ask what they can do to help, be honest and specific about what you’d like^[25].

Support groups are a great way to link up with others who have mantle cell lymphoma or other cancers. Because mantle cell lymphoma is a rare type of blood cancer that few people are familiar with, it’s common for those who have it to feel isolated. Other people who’ve dealt with mantle cell lymphoma understand your experience. Their experiences can help you know what to expect^[25].

You may feel more comfortable talking openly with support group members than with your family members or friends. Some support groups meet in person, while others gather online^[25].