Mantle cell lymphoma


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Mantle cell lymphoma

Mantle cell lymphoma is an aggressive variety of lymphoma which is typically found in the lymph nodes, spleen, marrow and blood.  It is unique in that it is classified as an aggressive variety of lymphoma and yet it sometimes behaves as an indolent lymphoma. Most typically it behaves aggressively and is more difficult to treat than other indolent lymphomas.

Mantle cell lymphoma is called that because it usually infiltrates the Mantle Zone of the lymph nodes. That is the area surrounding the lymphoid follicles. When it remains in the mantle zone it generally follows a more indolent course. When it spreads outside this area, in a more diffuse growth pattern, its behaviour becomes less indolent and more aggressive.


Diagnosis and Prognosis

It is typically characterized by the expression of CD5, over expression of Cyclin D1 and the t(11:14) chromosomal translocation.

Historically mantle cell lymphoma has had a much poorer prognosis than other types of lymphoma, with a median survival of only 3-5 years. Newer chemotherapy protocols, and stem cell transplants have made marked improvements in survival.  In the era of Rituximab the median survival has improved significantly and many studies report median survival of over 7 years.

Recent discoveries have shown that the most important prognostic factor is the proliferation index as measured by the MIB-1 and Ki-67 expression. Those patients with a proliferation index below 30% have a dramatically higher survival rate. After 5 years disease free, relapses in this population group are rare and a very high percentage of patients are in this group. Those with a proliferation index above 30% generally have a much poorer prognosis. The link below will take you to a virtual education video that reviews the prognosis, and treatment of mantle cell lymphoma, the role of the proliferation index, and the prospect of a cure.

Mantle Cell Lymphoma, is there a potential for a cure; from Clinical Options

Here is a somewhat technical review of the diagnosis and bio-pathology of mantle cell lymphoma from Haematologicia.

Biology and bio-pathology of mantle cell lymphoma



Note: The drug Ibrutinib is a very new drug that is still in many clinical trials. It was given accelerated approval by the USA FDA in November 2013 so we do not present a great deal of information about it on this page. Please check out our MCL abstracts page for studies about Ibrutinib and other promising treatments for MCL.

Mantle cell lymphoma is generally treated as an aggressive type of NHL and aggressive combination chemotherapy is used. Nevertheless in some selected cases it presents as an indolent lymphoma and watch and wait may be appropriate in these cases. 

Historically R-CHOP or R-HyperCVAD have been the primary first line of treatment. Studies seemed to indicate that R-HyperCVAD had a slight advantage in terms of remission rates and duration of remission. Proceeding directly to an autologous stem cell transplant produces even better results, and is being done more frequently. This first study indicates that both R HyperCVAD and autologous SCT provide a superior outcome to R-CHOP.

Effect of front-line therapy with either high-dose therapy and autologous stem cell rescue (HDT/ASCR) or dose-intensive therapy (R-Hypercvad) on outcome in mantle cell lymphoma (MCL)

More recently it has been found that ARA-C adds a significant benefit to the progression free survival.  This first study examines current thinking in frontline treatments for mantle cell lymphoma. They find that adding ARA-C (Cytarabine) to chemotherapy appears to  add a significant progression free survival advantage.

Front-line treatment of mantle cell lymphoma

The next study from the ASH 2010 convention examines the role of ARA-C (Cytarabine) in the treatment of mantle cell lymphoma. It also shows that adding ARA-C provides a significant survival benefit.

Alternating Courses of 3x CHOP and 3x DHAP Plus Rituximab Followed by a High Dose ARA-C Containing Myeloablative Regimen and Autologous Stem Cell Transplantation (ASCT) Is Superior to 6 Courses CHOP Plus Rituximab Followed by Myeloablative Radiochemotherapy and ASCT In Mantle Cell Lymphoma: Results of the MCL Younger Trial of the European Mantle Cell Lymphoma Network

Bendamustine is beginning to show some excellent results, just as is does with follicular lymphoma. It is perhaps a bit too early to say we should abandon R-CHOP or R-HyperCVAD in favour of Bendamustine but that may turn out to be what happens in the future.  This first study looks at Rituxan, Bendamustine and Cytarabine (Cytarabine is another name for ARA-C)  for MCL patients who are not eligible for an SCT. The response rate is extremely impressive.

Combination of Rituximab, Bendamustine, and Cytarabine for Patients With Mantle-Cell Non-Hodgkin Lymphoma Ineligible for Intensive Regimens or Autologous Transplantation

The following MS PowerPoint slide set helps sort out all the various treatment approaches and put them into perspective. You need to create a free account with Clinical Care Options to download them, but it is well worth the effort. The series is presented by  Dr. Owen A. O'Conner who is Professor of Medicine and Pharmacology Deputy Director for Clinical Research and Cancer Treatment NYU Cancer Institute

Multidisciplinary Approaches for the Diagnosis and Optimal Treatment of MCL

The following is a single page chart reviewing the opinions of 10 of the foremost experts in treating mantle cell lymphoma. It asks each expert to answer the 4 questions below, and their opinions are presented in a chart. Just hover over the question for each doctor to read their answer.

  1. What is your most common induction regimen for a younger patient (under age 60) with MCL?
  2. What is your most common induction regimen for an older patient (over age 75) with MCL?
  3. Do you generally recommend maintenance therapy for patients with MCL?
  4. Do you use bortezomib or lenalidomide in the treatment of MCL? In which situations?

Read their answers here

A recent small study found dramatically high survival rates with a different chemotherapy regimen. At 3 years the progression free survival was 78%. While it is a small study it is worth considering for someone who is newly diagnosed. Below is a link to that study. 

Due to the fact that Mantle cell lymphoma generally has a worse prognosis than other aggressive types of NHL, consolidation therapy is strongly indicated. Consolidation simply means that as soon as the primary therapy is completed another therapy is initiated in order to "consolidate" the response in order to attempt to achieve a complete remission that is very durable.  The most common form of consolidation therapy for most of the indolent types of lymphoma is maintenance Rituxan. It has also been shown that maintenance Rituxan dramatically improves the overall survival and progression free survival for mantle cell lymphoma patients. To view the following medical paper about maintenance Rituxan from Medscape you will need a free Medscape account.

Maintenance Rituxan of benefit in mantle cell lymphoma

Two other types of consolidation therapy are common. A stem cell transplant (see below) for those who are eligible, and radioimmunotherapy such as Zevalin or Bexxar. Read the study below which shows the dramatic improvement in response when consolidation therapy is used.

Survival benefit of post induction consolidation therapy in MCL (mantle cell lymphoma): A Polish Lymphoma Research Group (PLRG) retrospective multicenter analysis.


Stem cell transplants are often used, either for as consolidation therapy as noted above, or for relapsed MCL. This is becoming more common as results from studies show it offers a good opportunity for long term survival. Here is a link to a recent study about using an SCT with in-vivo Rituxan purging. With a 70% overall survival at 6 years it is a remarkable improvement over past options.

Long-term progression-free survival of mantle cell lymphoma after intensive front-line immuno-chemotherapy with in vivo–purged stem cell rescue

Nevertheless stem cell transplants are a very aggressive approach and may not be necessary as newer more effective treatments have been developed in the past decade, including Bortezomib, and Ibrutinib.  What follows are two items. The first is an abstract that shows a benefit from either autologous SCT or a reduced intensity allogeneic SCT. That is followed by a peer review of that paper by another expert in the field He discusses at length the issues regarding SCT and why it may or may not be the best option.

Autologous or Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Chemotherapy-Sensitive Mantle-Cell Lymphoma: Analysis of Transplantation Timing and Modality

The peer review

Is Early Hematopoietic Stem-Cell Transplantation Necessary in Mantle-Cell Lymphoma?


Another treatment that has excellent results is Bortezomib (brand name Velcade) in many studies.

Here is an article from Annals of Oncology that reviews the current status of MCL treatments.

Current treatment standards and future strategies in mantle cell lymphoma

The following article is from the Blood Journal. It describes the current status of MCL biology and treatments.

How I treat MCL. Drs. Michele Ghielmini and Emanuele Zucca

Click here for a list of medical abstracts about the latest treatments for Mantle Cell Lymphoma



Other information

For a detailed look at Mantle Cell Lymphoma visit this site.


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