What Is Mantle Cell Lymphoma?

Overview

Mantle cell lymphoma is a rare type of non-Hodgkin’s lymphoma, a blood cancer affecting the lymphatic system.1 Lymphomas specifically target the blood cells that are responsible for fighting off infection and maintaining the functioning of the immune system.  These can be broadly divided into two families, Hodgkin’s and non-Hodgkin’s lymphoma, depending on the presence or absence of Hodgkin’s (Reed-Sternberg) cells during diagnosis.²

Mantle cell lymphoma gets its name from where the cancer starts and how these malignant cells originate from an area of the lymph node called the mantle zone. These B-lymphocyte cells become cancerous and replicate uncontrollably, where they are then free to spread throughout the body.² The site(s) they affect will ultimately determine the course of the disease, including the symptoms experienced.¹

Unlike other Non-Hodgkin’s lymphomas, Mantle cell lymphoma has the potential to be either fast or slow-growing (‘high-grade’ or ‘low-grade’ respectively) and can be divided into subsets of disease:¹

Nodal mantle cell lymphoma: Most cases of Mantle cell lymphoma present as ‘nodal’. This means that they primarily affect the lymph nodes.¹ However, this type of Mantle cell lymphoma is typically very aggressive and can rapidly grow to affect multiple sites in the body. A specific ‘blastoid’ type of this nodal lymphoma proves to be even more severe and is linked to a very poor prognosis.^1,3

Leukaemic non-nodal mantle cell lymphoma: This type of Mantle cell lymphoma accounts for around 10% of cases and can often be described as ‘Indolent’, meaning it causes very little pain, if any.⁴ This form of lymphoma is slow-growing and, in some cases, may lie in wait like a dormant volcano for up to a decade.⁵ At first glance, it can mimic other slow-growing blood cancers (such as chronic lymphocytic leukaemia), and due to its unaggressive behaviour, it may not cause symptoms or have any dramatic effects to warrant treatment.⁶ 

Causes of mantle cell lymphoma

Mantle cell lymphoma, like numerous blood cancers, results from unfavourable genetic mutations within cells.  The most important mutation is the altered location of the gene CCND1. This gene is vital to the healthy functioning of cells, and translocation leads to excessive levels of the protein Cyclin D1. This increase in Cyclin D1 then causes the accelerated replication of lymphoma (cancerous) cells, meaning that the cancer can rapidly progress.  Several other genetic markers are linked to mantle cell lymphoma, such as SOX11 overexpression, as well as mutations in a gene called TP53. However, the extent of the impact that these have on mantle cell lymphoma is not fully understood.⁶

Risk factors

Lymphomascannot be transferred from person to person. There is no identified single cause of lymphoma. However, there are several factors that may increase the risk of developing it:

• Being of caucasian ethnicity¹ 
• Age¹
• Being genetically male¹
• Viral infections such as Epstein-Barr Virus, Hepatitis B and Hepatitis C⁷ 
• Infection with Borrelia burgdorferi, an organism linked to Lyme disease⁸

Signs and symptoms of mantle cell lymphoma

Mantle cell lymphoma, like many lymphomas, may present with non-specific symptoms:⁹

• Non-painful swelling of lymph nodes
• Extreme tiredness
• Loss of appetite 
• Itchy skin

As well as ‘B-symptoms’, which act as an indicator of severe or advanced disease:⁹

• Night sweats
• Fevers
• Unintended weight loss (around 10% of body weight within 6 months)

You may also experience symptoms related to specific areas in which the lymphoma has spread, for example:¹⁰

• Bleeding from within your stomach changes in bowel habits or obstruction of bowels following spread to the Gastrointestinal tract
• ‘Tummy’ discomfort due to an enlarged spleen or liver
• Nausea
• Shortness of breath or coughing if the cancer is affecting the lungs

Diagnosis

Mantle cell lymphoma is particularly difficult to diagnose promptly. Its appearance is highly variable, and patients with the same disease may present very differently from one another.  

It is understood that the majority of patients with mantle cell lymphoma present with late-stage disease, where the cancer has already spread from the lymph nodes across numerous sites within the body.¹¹ Arguably, the non-specific symptoms and rapid progression of the disease (in some cases) can make for an unpredictable diagnosis and treatment plan. 

However, commonly used tests in the diagnosis of mantle cell lymphoma include:

• Biopsy of the affected area: Biopsy of either an affected lymph node, organ, or bone marrow will allow for assessment of the affected area for lymphoma cells and a confident diagnosis to be made.¹
• Positron Emission Tomography (PET): PET is a radioactive imaging technique that can be used to identify areas where glucose uptake is high and is suggestive of potential cancer activity.¹
• Fluorescence In Situ Hybridisation (FISH): This is a test to identify worrying DNA rearrangements within sampled cells that may be linked to mantle cell lymphomas as above.¹
• Flow cytometry with Immunohistochemistry: This technique can be used to assess potential lymphoma cells in greater detail.^1,5 As these cells may visually mimic other lymphomas/leukaemias, a more comprehensive view can help differentiate between them. Immunohistochemistry involves assessing the cells for the presence of cancerous markers of lymphomas.¹
• Endoscopy: To view the inside of your bowels or stomach if the lymphoma is affecting these areas.¹

Management and treatment for Mantle cell lymphoma

Options for treatment are dependent on the person, as Mantle cell lymphoma does not have a standardised method of treatment and is unfortunately deemed ‘incurable’. This is not to say that the patient cannot be successfully cared for; it is just that this condition tends to eventually return. Ultimately, the choice of management may be guided by factors including:

• Age¹
• Lactate Dehydrogenase (LDH) levels can be measured using a blood test.¹
• White blood cell count¹
• Performance status (how your disease affects a patient's ability to care for themselves)¹

The above factors can then be used to calculate a MIPI score, which is used to assess the prognosis to guide care.¹ This may also be used in combination with other separate factors such as the KI-67 index, cytogenetics, or TP53 gene mutations, which are all believed to be linked to the outcomes of disease.¹ The diverse nature of the disease means that the treatment of Mantle cell lymphoma will be tailored to individual needs and should be decided on by collaboration between the patient and the healthcare team.

As with many blood cancers, management often consists of two distinct phases termed induction and consolidation. Induction will aim to kill cancerous lymphoma cells in the initial stages, whereas consolidation aims to kill cancer cells that may evade capture in follow-up tests.⁴ Consolidation is aimed to prevent the lymphoma from coming back for as long as possible.⁴

Generally, the overall treatment plan will be heavily dependent on whether the patient is fit enough for a stem cell transplant, as this will often play a central role in effective lymphoma care.⁴

Chemotherapy

Chemotherapy treatment will depend on the level of intensity desired and how fit the patient.⁴ It is commonly used with the immunotherapy medicine Rituximab in combination with several other chemotherapy medicines. For most cancers, treatment would usually stop after consolidation when the patient is in complete remission (free from cancer). For Mantle cell lymphoma, however, those who have shown a good response to the initial stages of treatment may be recommended to continue immunotherapy with Rituximab for many years.⁹

Stem cell transplant

Stem cell transplants work by replacing stem cells that have become damaged due to the effects of chemotherapy.¹² This then aims to restore the function of the bone marrow by replenishing the body’s stem cells.¹³ In the case of Mantle cell lymphoma, autologous stem cell transplant (stem cells taken from the patient’s own blood or bone marrow) combined with chemotherapy is usually the preferred method of treatment.⁴  However, the difficulty lies with the intensity of stem cell transplantation, especially as the age of people presenting with Mantle cell lymphoma often makes this unsuitable. 

Radiotherapy

Radiotherapy works by using radiation energy to cause DNA damage and, hence, targeted cell damage.¹³ By damaging the cell’s DNA, the cancerous cells are prevented from replicating and ultimately die. This mode of treatment can prove successful in killing cancers, especially when only specific sites of the body are affected. Therefore, due to people presenting for diagnosis late and the typical widespread nature of the disease at this point, radiotherapy may not be an option for treating Mantle cell lymphoma. However, those in the early stages of disease (I or II) with the absence of ‘bulky disease’ may benefit from this.⁴ Despite radiotherapy’s success when used in these groups, treated Mantle cell lymphoma is very likely to eventually return, needing other methods of treatment to be used in the future. 

Watchful waiting

Occasionally, the patient may be in a position where active treatment is not necessary (in slow-growing disease).4 For these people, close observation may be the best option as this will allow them to avoid the adverse effects of treatment for as long as possible until the situation changes.⁴

Complications

There are several potential complications as a result of the disease, and these will largely depend on where the disease has spread. Complications such as blood clots, blockage, bleeding or rupture of the Gastrointestinal tract, amongst other conditions, including tumour lysis syndrome, can occur. There are also, unfortunately, several potential adverse effects seen with treatment, such as reductions in important blood cells, nausea, vomiting, diarrhoea, hair loss, infertility, as well as potential permanent damage to the heart, lungs or nerves.¹ 

Each form of treatment carries individual side effects, some of which have the potential to be fatal or permanent.¹ Hence, it is important to consult a healthcare professional for guidance on any specific adverse effects that may be linked to treatment. Ultimately, the healthcare team will try their best to mitigate these where they can. 

The most notable complications are:

Reductions in Blood cells: In successfully treating Mantle cell lymphoma, it is important to be aware of the balance required for killing cancerous cells versus ensuring that essential blood cells are not decimated.¹  The cancer treatments outlined above may carry a risk of harm by increasing bleeding risk as well as reducing the body’s ability to fight off infection. These treatments also have the potential to damage healthy cells and are thought to be linked to an increased risk of secondary ‘therapy-related’ cancers further down the line.

Tumor lysis syndrome: This is a serious complication that can be associated with both the disease and its treatment. It is considered an emergency and occurs when the contents of cancer cells leak into your blood (especially when they are destroyed). This may result in kidney damage and potentially fatal changes in the heart’s rhythm.¹⁴

Summary

Mantle cell lymphoma does not have a one-size-fits-all presentation, behaviour or treatment, which makes its management particularly challenging. With that being said, there are several different avenues for the care of people with this cancer, avenues which can be moulded to the needs of those affected. As individuals, we must take our health into our own hands and be comfortable in reaching out for medical advice if experiencing any of the concerning symptoms touched on within this article. Early identification and intervention are crucial in improving the prognosis for those with this rare blood cancer.