Mantle cell lymphoma (MCL) is a type of cancer that arises in cells of the immune system. It is a rare disease that affects approximately one in 200,000 people. Most commonly diagnosed in older adults, MCL is often an aggressive disease that requires early diagnosis to improve treatment outcomes.
Lymphomas can be broadly categorized into two groups, Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). MCL is a form of NHL and makes up between 5 percent to 7 percent of all NHL cases. MCL originates in a type of white blood cell called B lymphocytes or B cells and is therefore a form of B-cell lymphoma. MCL is generally an aggressive (fast-growing) disease that often develops in the gastrointestinal (GI) tract and bone marrow. A small subset of affected individuals may be diagnosed with an indolent (slow-growing) form of the disease. MCL is fairly rare and is often not diagnosed until it is in the late stages of the disease.
B cells are part of the immune system, and their role is to help the body recognize and fight infection. B cells congregate in the lymph nodes, including a region of the lymph node known as the mantle zone. However, genetic abnormalities can develop and lead to uncontrolled multiplication of B cells in the mantle zone, giving rise to MCL.
The genetic feature most strongly linked to MCL is the disruption of a protein called cyclin D1. A chromosome error may cause levels of the cyclin D1 protein to be too high or overexpressed. This is observed in about 98 percent of MCL cases and is considered a molecular hallmark, or key distinguishing feature, of cancer. The link between cyclin D1 overexpression and MCL is so strong that cyclin D1 levels are measured as part of the diagnosis.
MCL shares many symptoms with other forms of B-cell lymphoma, including the following:
Additional symptoms of MCL may include:
In order to confirm a diagnosis, a doctor needs to perform a medical examination, including some of the following tests.
During a physical exam, a doctor will check externally for swollen lymph nodes and confirm other disease symptoms.
A lymph node biopsy involves a doctor examining a lymph node for the presence of cancer cells. This can be a surgical biopsy that involves removing an entire lymph node from the body or a needle biopsy that involves the removal of a portion of a lymph node. MCL can be distinguished from other forms of B-cell lymphoma by the shape of the cancerous B cells, observable under a microscope.
Immunohistochemistry (IHC) involves manipulating specific proteins in a tissue sample to make them visible under a microscope. IHC can be used to detect and measure levels of the cyclin D1 protein, which is important to confirm the diagnosis of MCL. Levels of another protein, SOX11, may also be measured as it is involved in rare cases of MCL that are negative for cyclin D1.
Blood tests can be used to check a person for signs of MCL, which may include low counts for red blood cells, white blood cells, or platelets (cell fragments central to blood clotting).
Doctors often use imaging techniques such as CT or positron emission tomography (PET) scans to look for evidence of cancer in the body. These imaging tests may be used to check for cancer in swollen lymph nodes in the chest, abdomen, or pelvis.
During a bone marrow biopsy, a doctor uses a needle to withdraw tissue from the bone marrow and collects a tissue sample. The samples are analyzed under a microscope for the presence of cancer cells.
Endoscopy of the GI tract is a procedure that involves the insertion of a long flexible tube equipped with a light and a camera to view inside the throat, stomach, or intestines. Endoscopy may be recommended in patients with MCL who present with GI symptoms.
There are many treatment approaches for MCL including:
Chemotherapy is the primary treatment for aggressive MCL. It can be administered as a single drug, such as Treanda (bendamustine), or as a combination of different drugs.
One common combination known as CHOP consists of four specific chemotherapy drugs: cyclophosphamide (Cytoxan), doxorubicin hydrochloride (also known as hydroxydaunorubicin and sold as Adriamycin), vincristine (Oncovin), and prednisone.
Another common chemotherapy treatment known as hyper-CVAD is a combination of cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate, and cytarabine. Chemotherapeutic drugs may be used alone or together with the antibody drug Rituxan (rituximab) as part of a treatment regimen for mantle cell lymphoma.
Radiation, alone or in combination with chemotherapy, may be given to people diagnosed with early-stage MCL.
Immunotherapy uses the immune system to fight cancer cells. Different forms of immunotherapy might be used to treat MCL, including antibodies and CAR T-cell therapy.
Antibodies are proteins that recognize specific molecules, called antigens, that are present on the surface of certain cells. As part of the immune system, antibodies can bind to foreign antigens and target those cells to be destroyed. Rituxan is an antibody drug that has been engineered to recognize antigens on the surface of B cells, thereby specifically attacking the cancer cells. Rituximab is often used in combination with individual chemotherapy drugs like bendamustine. It can also be used together in a treatment regimen with CHOP or hyper-CVAD chemotherapy, which is known as R-CHOP or R-hyper-CVAD.
CAR T-cell therapy is a newer kind of treatment that involves removing immune cells called T cells from a person with cancer and engineering them to contain receptors called chimeric antigen receptors on the surface of the cells. The CAR T cells are then put back into the individual, where they can bind to antigens on B cells. In this way, CAR T-cell therapy uses the person’s immune system to specifically attack the cancer cells. Tecartus (brexucabtagene autoleucel) is a type of CAR T-cell therapy that has been recently approved by the U.S. Food and Drug Administration for cases of MCL that have failed to respond well to other treatments.
Targeted drugs work by targeting and inhibiting a specific protein or group of proteins. Velcade (bortezomib) is a type of targeted drug known as a proteasome inhibitor and is used as a treatment for MCL, either alone or in combination with chemotherapy and rituximab.
A stem cell transplant, also called a bone marrow transplant, involves replacing the bone marrow of a person receiving treatment, which allows their body to withstand higher doses of chemotherapy. Stem cell transplantation can be either allogeneic or autologous. An allogeneic stem cell transplant involves obtaining bone marrow from a healthy donor, whereas an autologous stem cell transplant involves obtaining stem cells from the person’s own body. A stem cell transplant may be recommended for healthy individuals with MCL who have responded to chemotherapy.
Rarely, MCL may be diagnosed as an indolent, or slow-growing, form of the disease rather than the typical aggressive cancer. For this form of MCL, doctors may opt to take a watch-and-wait approach and will keep an eye on the disease through regular visits to monitor its progression. This allows treatment to start promptly if cancer begins to grow more quickly.
Treatment options that are specifically designed to be effective against MCL are limited. Therefore, people diagnosed with MCL may be able to take part in a clinical trial to explore newer, more effective potential treatments.
MCL is often an aggressive disease that is typically not diagnosed until the late stages. Therefore, the prognosis for the condition remains poor with an overall survival rate of four to five years. After initial treatment response and remission, many people with MCL experience relapse, where cancer returns after a while. Newer treatments are being explored in clinical trials to achieve better treatment outcomes and improve the survival of people living with MCL.
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