What is Mantle Cell Lymphoma?
Mantle cell lymphoma (MCL) is a rare kind of non-Hodgkin lymphomas, which are types of cancer that start in the white blood cells called lymphocytes. MCL is identified by a specific gene abnormality where a segment from chromosome 11 switches with a segment from chromosome 14, causing the overproduction of a protein called cyclin D1. This abnormality offers a clue to its diagnosis, albeit not always straightforward due to the variety of its appearances. Some cases of MCL are straightforward, while others are more difficult to diagnose. Generally, MCL progresses fast (referred as aggressive MCL), but there’s also a type that grows slowly (referred as indolent MCL).
What Causes Mantle Cell Lymphoma?
Mantle cell lymphoma is usually random, but it might occur more often in certain families.
Risk Factors and Frequency for Mantle Cell Lymphoma
Mantle cell lymphoma (MCL) is a less common type of B-cell non-Hodgkin lymphoma. Each year, only one in 200,000 people are diagnosed with it. Despite being a rare condition, it accounts for about 5% of all non-Hodgkin’s lymphomas. It is more likely to occur in men, with three men affected for every woman. People are generally diagnosed with MCL when they are between 60 and 70 years old.
Signs and Symptoms of Mantle Cell Lymphoma
Mantle cell lymphoma (MCL), a type of cancer, often presents as widely spread throughout the body at the time of diagnosis. This cancer has several typical features, including:
- Widespread enlarged lymph nodes
- Fevers
- Night sweats
- Weight loss
- Discomfort due to an enlarged spleen
- Changes in the blood counts because of bone marrow involvement
- Symptoms due to the disease spreading to other organs (extranodal involvement)
Extranodal involvement, where the disease affects other organs like the gastrointestinal tract, the spleen, and the bone marrow, is quite common in MCL. MCL has characteristics of both slow-growing (indolent) and fast-growing (aggressive) cancers.
Testing for Mantle Cell Lymphoma
Mantle cell lymphoma (MCL), a type of cancer, can be diagnosed through a procedure called excisional biopsy, which involves removing a lymph node or affected tissue from outside the lymph nodes to be examined. To support this, your doctor might also order some lab tests including a complete blood count with differential, lactate dehydrogenase (LDH), and beta-2 microglobulin. A bone marrow biopsy, which is when a small amount of bone marrow is removed for testing, and imaging tests like CT or FDG-PET/CT scans might also be needed. These tests help your doctor understand your body’s condition in more detail.
Based on these tests, your doctor might look at your Ki-67 index, an indicator of how fast cells are growing and dividing, and mutation status of p53, ATM, and CCND1, which are all genes that can play a role in cancer. If your doctor suspects that your nervous system might be involved, they may also perform a cerebrospinal fluid (CSF) study. This is particularly important if your Ki-67 index is high (over 30%), you have a blastoid variant of MCL, or if you’re experiencing neurological symptoms.
Even though MCL often affects the gastrointestinal (GI) tract, you may not require an endoscopic evaluation which involves using a thin tube with a light and camera attached to visually examine your digestive tract. However, this examination might be necessary if your doctor suspects early-stage MCL.
Further, doctors would use a process called immunohistochemistry to help differentiate MCL from other Non-Hodgkin’s lymphomas. This test looks at the proteins in the cells in your tissue samples. Certain markers can indicate MCL, such as B-cell markers cyclin D1 and SOX11. These help distinguish MCL from other lymphomas. It’s important to know that not all cases of MCL will test positive for Cyclin D1, even though it’s a common marker for the disease.
To make a treatment plan, doctors often use a scoring system, such as the MIPI (Mantle cell lymphoma international prognostic index). This scoring calculates your risk and prognosis based on your age, general health status, LDH level, and white blood cell count. This scoring can help doctors predict patient outcomes. For example, high-risk patients, based on the MIPI, have an average survival time of 2.8 years, while low-risk patients may live more than 5 years.
However, this scoring doesn’t cover all possible factors and might not be fully accurate for all patients, so doctors also consider other factors like the Ki-67 index, cytogenetics, and TP53 mutations, which can all provide a better view of the risk.
Doctors also classify patients into two major categories: indolent (slow-growing) MCL and aggressive MCL based on their symptoms and lab results, such as the Ki-67 index and MIPI score, as well as genetic factors.
Treatment Options for Mantle Cell Lymphoma
Mantle cell lymphoma (MCL) is a type of cancer that affects a certain kind of white blood cell. Even with medical advances and treatments, MCL remains difficult to cure. How long a person lives after being diagnosed depends highly on whether the disease is aggressive (fast-growing) or indolent (slow-growing). This can range from 1.8 to 9.4 years.
In making treatment decisions, doctors consider various factors. These include how aggressive the disease is, the person’s health and age, and their Mantle Cell International Prognostic Index (MIPI) score. The MIPI score measures the severity of the disease, helping the doctor choose the right treatment approach.
If the MIPI score is low and the MCL is slow-growing, doctors may delay treatment and monitor the disease progression instead. This approach, known as “watch and wait”, would typically be applicable where the maximum tumor size is less than 3 cm, the blood test for an enzyme called lactate dehydrogenase (LDH) is normal, and the patient is not experiencing certain symptoms called “B symptoms”.
For more aggressive forms of MCL, various chemotherapy treatments can be used. These treatments use special drugs that can slow down or stop the growth of cancer cells. Doctors will decide on the most suitable method based on the patient’s overall health and whether they are eligible for a bone marrow (stem cell) transplant. Some patients can receive a stem cell transplant, which involves replacing diseased or damaged marrow with healthy stem cells.
Additionally, there are other therapies including the use of specific drugs to target the cancer cells. Examples of these include Ibrutinib, zanubrutinib, acalabritinib, and Venetoclax, which are medications that help block certain proteins in the cancer cells, slowing their growth and spreading.
New treatments are ongoing investigations in clinical trials, and some of these include Polatuzumab, inotuzumab, pinatuzumab, loncastuximab and naratuximab – which are drugs that target specific proteins or growth factors in the cancer cells. One such emerging treatment is the chimeric antigen receptor T cell (CAR-T) therapy, which modifies the patient’s own immune cells to target and destroy the cancer.
These treatment options have been approved through the Food and Drug Administration (FDA), based on the successful results and survival rates from clinical studies. Remember, the treatment for MCL depends highly on the individual’s health and the characteristics of the cancer itself. It’s always best to discuss these options with the healthcare provider to determine the most suitable treatment approach.
What else can Mantle Cell Lymphoma be?
When doctors try to figure out if someone has mantle cell lymphoma, they often think about two main possibilities: SLL/CLL and DLBCL. Both of these conditions are types of mature B-cell lymphomas that express a protein called CD5, making them difficult to tell apart just by using flow cytometry, a cell analysis technique.
However, there are subtle clues that can help doctors arrive at a correct diagnosis. If the cells test positive for both CD200 and CD23, it’s more likely to be SLL/CLL. On the other hand, mantle cell lymphoma cells typically express FMC7 and do not express CD23.
Getting a definite answer usually requires more specific tests. These can involve finding a particular chromosome rearrangement known as t(11;14) using a technique called FISH, or detecting the presence of proteins called cyclin D1 and SOX11 on the cells using a different method called immunohistochemistry.
Cells that express cyclin D1 and SOX11 uniformly usually indicate mantle cell lymphoma. However, cyclin D1 can sometimes show up in small areas of SLL/CLL, so its presence doesn’t automatically mean that the person has mantle cell lymphoma. Finally, if the cells are large and don’t express cyclin D1 or SOX11, it’s possible that the person has a condition called diffuse large B-cell lymphoma.
If the structure of a lymph node remains intact and only contains few scattered cyclin D1 positive abnormal cells, doctors might consider a diagnosis of mantle cell neoplasia in situ, a precancerous condition.
Surgical Treatment of Mantle Cell Lymphoma
The suggestion for diagnosing these conditions is often through a procedure called an Excisional Biopsy. However, the use of surgery as a way to treat the condition may not always be the best approach. This is mainly because the disease affects the entire body system, rather than being confined to one specific area.
What to expect with Mantle Cell Lymphoma
The International Prognostic Index (IPI) has not been successful in predicting the outcome in patients with Mantle Cell Lymphoma (MCL), which is a type of cancer. However, a newer method called the MCL IPI (MIPI) has shown some promise. This method takes into account the patient’s age, health status, blood test results, and white blood cell count. Using this information, doctors can classify patients into three risk groups: low, intermediate, and high risk. These groups have a predicted survival rate of 60%, 35%, and 20% after five years respectively.
Two other methods were created recently to improve predictions. These take into account a protein called Ki-67 (MIPIb) and use a simpler calculation (sMIPI), however, these methods still need more clinical validation. Additionally, the deletion of two genes, CDKN2A and TP53, have linked with lower survival rates, regardless of the Ki-67 protein levels. These two genes were identified in studies involving patients who had received an autologous stem cell transplant, which is a procedure where a patient’s own stem cells are used to replace damaged cells. Overexpression of TP53 correlates with a worse prognosis or outcome.
Patients who have cancer cells in the peripheral blood and bone marrow (also known as leukemic non-nodal MCL) may have a slower disease progression.
Possible Complications When Diagnosed with Mantle Cell Lymphoma
MCL, or Mantle Cell Lymphoma, can lead to a host of complications depending on where it’s located in the body. Complications include rupture of the spleen due to an enlarged spleen, gastrointestinal bleeding or blockage or perforation if the MCL is in the digestive tract, and tumor lysis in a type of MCL called ‘blastoid variant’.
There can also be complications from chemotherapy and stem cell transplants. These can include life-threatening infections, neutropenic sepsis (a severe infection usually caused by bacteria), cytopenias necessitating transfusions, nausea, vomiting, and hair loss.
Some approved drugs for MCL, such as ibrutinib (aBTK inhibitor), can cause hypertension, arrhythmias, diarrhea, skin rashes, and increased risk of bleeding. These side effects are thought to be caused more by the drug’s off-target actions on EGFR (epidermal growth factor inhibitor), ITK (interleukin-2-inducible T-cell kinase), and PI3K (phosphoinositide 3-kinase). Second-generation BTK inhibitors like acalabrutinib and zanubrutinib are more specifically targeted at BTK and have fewer off-target side effects like hypertension, arrhythmias, or rashes.
The BCL-2 inhibitor venetoclax is approved for MCL but can cause tumor lysis syndrome. Lenalidomide can cause edema (swelling caused by excess fluid), cytopenias, risk of blood clots, and diarrhea.
Finally, treatments such as brexucabtagene (a type of CAR-T cell therapy ) can lead to complications such as encephalopathy (brain disease), cytopenias, and pyrexia (fever) as a result of cytokine release syndrome.
MCL Complications:
- Splenic rupture due to splenomegaly
- GI bleeding, obstruction or perforation
- Tumor lysis for ‘blastoid variant’
- Life-threatening infections
- Neutropenic sepsis
- Cytopenias needing transfusions
- Nausea, vomiting, hair loss due to chemo and stem cell transplants
- Hypertension, arrhythmias, diarrhea, skin rashes, bleeding risk due to ibrutinib
- Hypertension, arrhythmias, rashes from second-generation BTK inhibitors like acalabrutinib and zanubrutinib
- Tumor lysis syndrome from venetoclax
- Edema, cytopenias, risk of blood clots, diarrhea due to lenalidomide
- Encephalopathy, cytopenias, pyrexia due to brexucabtagene
