Ask Question
   Sign Guest book

Search Site
                                                        

 
About Lymphoma
| Advocacy | Art | CAM & Life Style | Clinical trials | Docs | Centers | Guidelines at Diagnosis | Side Effects | Support | Symptoms | Tests | Treatments | Types of Lymphoma

Independent of industry funding, PAL depends on your support!

tax deductible

Patients Against Lymphoma

 

Types of Lymphoma > Mantle Cell Lymphoma (MCL)

Last update: 04/20/2013

TOPICS:
 
Overview | Workup | Treatments | Clinical Trials |
Research News

TOPIC SEARCH: PubMed: Diagnosis | Review | Therapies | Prognosis

 About Lymphomas
Overview of genes and cancer

Lymphoma is a cancer

About Lymphoma - general

 Ann Arbor Staging 
  Extranodal notations  

 Diagnosis 

Host/tumor
interaction

Lymphatic System

Risk Factors

Statistics
 
Staging
 
Symptoms

 
 Guidelines at diagnosis
  
Treatments

  
Return to top

Mantle Cell Lymphoma

A cancer of b-cells (lymphocytes) that normally reside in lymph nodes.   

"Mantle cell" describes the cell type. B-cells arise from the bone marrow and mature or differentiate into many cell types that tend to migrate to different areas of the body. Most lymphoma results from an acquired (not inherited) injury to the DNA in the genes of a single cell. 

A hallmark of cancer cells is that they have growth and survival advantages over normal cells. There cell division is not balanced by cell death. The abnormal cells may eventually form lumps called tumors

See overview of MCL - 2012
update on diagnosis, risk-stratification, and clinical management

In the News:

bullet
April 2013: Pharmacyclics Completes Enrollment of Phase III Ibrutinib CLL Study and Phase II Ibrutinib MCL Study  ascopost.com
bullet
Medpage today: Combo Tx Gets Perfect Score in Mantle Cell Lymphoma http://bit.ly/12OInDA

"- A three-drug combination -- vorinostat (Zolinza), cladribine, and rituximab (Rituxan) -- led to a 100% response rate in a small study of patients with advanced mantle cell lymphoma."

Snip: "All of the 37 patients in the study had at least a partial response, and 32 met criteria for complete response, including more than 90% of the patients who received at least six cycles of the combination therapy.

After follow-up as long as 34 months, progression-free survival (PFS) could not be estimated, Kamal Sharma, DO, reported here at the American Association for Cancer Research meeting"
bullet
Visco C. J Clin Oncol.2013
R-BAC shows promise in mantle cell lymphoma http://bit.ly/16pBrj2 
bullet
MCL abstracts (96) - ASH 2012
bullet
Video - Patient Power: Dr. Peter Martin on Kinase Inhibitors Offer New Hope for Mantle Cell Lymphoma  http://bit.ly/KwigwH
bullet
MCL - Lancet: Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial
bullet
MCL - ASCO 2012 Mantle Cell lymphoma abstracts
bullet
MCL, relapsed - Haematologica: A multicenter phase II trial (SAKK 36/06) of single-agent Everolimus(RAD001) in patients with relapsed or refractory mantle cell lymphoma.
bullet
MCL - Haematologica. 2010 August; Front-line treatment of mantle cell lymphoma
bullet
MCL - JCO, 2009: Immunochemotherapy and Autologous Stem-Cell Transplantation for Untreated Patients With Mantle-Cell Lymphoma: CALGB 59909

"There is no clear plateau in the PFS curve, so it remains to be seen if any patients are cured with this treatment. The only proven potential cure for MCL at this time remains allogeneic hematopoietic stem-cell transplantation. 36"
bullet
MCL - ASH. 2006: Reduced-Intensity Regimens in Allogeneic Stem-Cell Transplantation for Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia   
bullet
MCL - Cancer: Post-treatment (not interim) PET scan status is highly predictive of outcome in mantle cell lymphoma patients treated with R-HyperCVAD

Also see http://1.usa.gov/trRECZ
bullet
MCL - Pub Med: Indolent mantle cell leukemia: a clinic-pathological variant characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa light chain restriction, and good prognosis
bullet
MCL - Weill Cornell, Dr. Martin: Update from ASH 2011: New treatments for mantle cell lymphoma are on the horizon
bullet
MCL -Weill Cornell, Dr. Martin: Update from ASH 2011: Rituximab improves survival in patients with mantle cell lymphoma
bullet
MCL - Blood: Addition of rituximab to chemotherapy alone as first-line therapy improves overall survival in elderly patients with mantle cell lymphoma
bullet
MCL – Cancer, 2010: Durable Responses with the Metronomic (low daily dose) RT-PEPC in Elderly Patients with Recurrent Mantle Cell Lymphoma
bullet
Prognostic Index Predicts Survival for Patients With MCL Autologous Stem-Cell Transplantation
bullet
Lugano Conference: Rituximab + Lenalidomide Prolonged Remission in Mantle Cell Lymphoma http://bit.ly/lVhZmJ
bullet
Rituxan maintenance: EHA 2011: Remission duration of lymphoma doubled

"Clinical research has shown that recurrence of Mantle Cell Lymphoma, a variant of malignant lymphoma, can be reduced by almost 50% in patients who receive maintenance treatment with the antibody rituximab. These results are presented by Dr Hanneke Kluin-Nelemans at the 16th Congress of the European
Hematology Association in London."


Also see Medcape item: http://www.medscape.com/viewarticle/744453

Incidence

Mantle Cell Lymphoma represents 4% to 8% of non-Hodgkin’s lymphomas. It primarily affects older individuals; males more than females by a ratio of about 4 to 1. The median age at diagnosis is approximately 58 years of age.
 


Diagnosis   

To make an accurate diagnosis of lymphoma, a biopsy must be performed by the surgical removal (resection) of a lymph node.  A fine needle aspiration may be performed if a lymph node is not accessible, but this is not considered a definitive way to determine the diagnosis.

A series of tests will then be performed to determine the characteristics of the cells.  If a malignancy is determine, these characteristics will allow your doctors to determine the appropriate treatments to use when needed.  

 


Workup (adapted from NCCN Guidelines 2010)

bullet

Staging tests:
 
bullet

CT of Chest/abdominal/pelvic with contrast of diagnostic quality

bullet

Bone marrow biopsy + aspirate to document clinical stage I_II disease

bullet

Useful in select cases:
 
bullet

Endoscopy/colonoscopy

bullet

Lumbar puncture (for blastic variant or CNS symptoms)

bullet

PET-CT scan

bullet

CT of neck
 

bullet

Physical exam:
 
bullet

Attention to node-bearing areas, including Waldeyer's ring

bullet

Examine size of liver and spleen

bullet

Performance status

bullet

B symptoms
 

bullet

Labs and tests:
 
bullet

CBC, differential, platelets,

bullet

LDH

bullet

Comprehensive metabolic panel

bullet

Hepatitis B testing

bullet

Useful in select cases:
 
bullet

Hepatitis C test

bullet

Uric acid

bullet

Beta-2-microglobulin
 

bullet

Treatment, age and gender specific:
 
bullet

MUGA scan / echocardiogram" 
(prior to anthracycline-based therapy)

bullet

Discuss fertility issues

bullet

Pregnancy testing in women of child-bearing age if chemo is planned

 


Workup   

See for details  e-medicine


Common symptoms

bullet

fatigue (anemia)

bullet

loss of appetite

bullet

feeling of fullness or discomfort due to enlarged liver or spleen

bullet

enlarged lymph nodes - painless swelling in the neck, armpit or groin - often in more than one group

Other symptoms may include night sweats, unexplained high temperatures and weight loss. These are known as B symptoms.

 

Resources

bullet
About  Emedicine | LLS
bullet
Mantle Cell Lymphoma: Background for physicians
Medscape.com (free login req.)

Mantle cell lymphoma (MCL), which represents approximately 6% of non-Hodgkin's lymphoma (NHL) cases, remains the most challenging lymphoma to treat. As a result, this is one of the most active areas of investigation in lymphoma, in terms of translational research as well as in the development of novel approaches, some of which will be highlighted in this review.
 
bullet
Non-Hodgkins Lymphomas - Clinical Practice Guidelines in Oncology 
nccn.org professionals pdf  (one-time free registration and login required)
bullet
Genetics  Cancer Genetics Web 
bullet
Mantle Cell Information Websites  mclresource.com/MCLAid 
bullet
CD5- Mantle Cell Lymphoma:  from American Journal of Clinical Pathology - Medscape (free login req.) 
 
"Mantle cell lymphoma (MCL) typically expresses B-cell antigens and CD5 and overexpresses bcl-1 protein. However, unusual cases of bcl-1+ and CD5- MCL have been observed, posing a practical challenge for correct diagnosis and management." 
bullet
Mantle Cell Lymphoma: Background  Medscape.com (free login req.)

Mantle cell lymphoma (MCL), which represents approximately 6% of non-Hodgkin's lymphoma (NHL) cases, remains the most challenging lymphoma to treat. As a result, this is one of the most active areas of investigation in lymphoma, in terms of translational research as well as in the development of novel approaches, some of which will be highlighted in this review.
Variants:
bullet
Limited-stage mantle-cell lymphoma  annonc.oxfordjournals.org 
H. A. Leitch1, R. D. Gascoyne2, M. Chhanabhai2, N. J. Voss3, R. Klasa1 and J. M. Connors
bullet
Indolent MCL with nodal involvement and mutated immunoglobulin heavy chain genes humanpathol.com

We present a case of an indolent MCL that was documented with cyclin D1 expression in a lymph node biopsy performed more than 12 years ago. The patient has peripheral blood involvement with a lymphocyte count in the reference range, variable thrombocytopenia, and minimal adenopathy but is otherwise well, never having received any antineoplastic therapy.
Treatments
Questions for your doctor
 Patients Against Lymphoma
General, Treatment & Side Effects, and Tests

&

Treatment Overview
Return to top

 


Treatment Articles

TOPIC SEARCH to keep current!      
PubMed:  Review | Therapies | Stem Cell Transplant 
 

  Google Scholar: MCL and Maintenance

Also see Protocols for Refractory Disease  PAL 
Clinical Trials for MCL  PAL

Reasons to be encouraged:  Our sense is that progress against MCL is advancing rapidly of late for many reasons.  What is most appropriate as therapy is highly individualized in MCL ... so do consult experts directly. We also suggest that MCL survivors inquire specifically about clinical trials. 

Overview on Treatment of MCL:

bullet
MCL 2012 update on diagnosis, risk-stratification, and clinical management
bullet
Current and Novel Therapies for Mantle Cell Lymphoma cme.medscape.com/ 

"The purine nucleoside analogues (PNAs) also have activity as single agents and in combination with rituximab; they are ideal regimens for older patients and patients who are not eligible for SCT. Recent studies in patients with relapsed MCL have shown substantial antitumor activity of bortezomib, the mTOR inhibitors temsirolimus and everolimus, the immunomodulatory drugs thalidomide and lenalidomide, and Bendamustine. Studies integrating these novel agents earlier in the disease course or in combination with each other will, we hope, produce more durable responses with less toxicity."

Stem cell rescue (transplant):

bullet
ARA-C incorporation into SCT (Nordic group) Protocol  

wpe1.jpg (66813 bytes) click to enlarge
bullet
The Nordic group's conclusion: "The addition of high dose ARA-C and Rituxan increased event-free, progression-free, and overall survival; that the molecular remission rate and the duration of remission was better; and interestingly - they collected stem cells after the therapy - the proportion of PCR-negative stem cell product was less. 

... that the 5-year event-free survival plateau of 63% suggests this treatment may be - and the editorial quotes here are my own, they are not in their presentation- Curative. But their suggestion is that progression-free survival is higher than anything we have seen before, so these are interesting data."  Dr. Gordon (NCCN updates)
bullet
~ Long-term progression-free survival of MCL following intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: 
A non-randomized phase-II multicenter study by the Nordic Lymphoma Group. Blood. 2008 Jul 14.  

full text bloodjournal.hematologylibrary.org


n = 160 consecutive, untreated patients younger than 66 years
bullet
MCL Can Be Cured by Intensive Immunochemotherapy with In-Vivo Purged Stem-Cell Support; Final Report of the Nordic Lymphoma Group MCL2 Study  ASH abstracts2view.com 

Conclusion: The demonstration of long-term event-free survival in a large, consecutive prospective series now for the first time indicates that intensive immunochemotherapy including AraC and Rituximab with in-vivo purged stem-cell support may cure mantle cell lymphoma.
bullet
The Role of Autologous Transplantation in the Management of Mantle Cell Lymphoma: A Study From the EBMT , E. Vandenberghe, et al.  PDF - mmserver.cjp.com
bullet
Review of :"Long-term remission in mantle-cell lymphoma following high-dose sequential chemotherapy and in vivo rituxan-purged stem cell autografting (R-HDS regimen)" Blood  Docguide.com  
bullet
The Role of Autologous Transplantation in the Management of Mantle Cell Lymphoma:   PDF  
bullet
" Mini " Transplants Effective in Recurrent Mantle Cell  cancerconsultants.com
bullet
Tandem Transplants:
Patients with mantle-cell lymphoma relapsing after autologous stem cell transplantation may be rescued by allogeneic transplantation. Bone Marrow Transplant. 2000 Sep;26(6):677-9. PMID: 11035375   PubMed
bullet
Hyper CVAD Followed by SCT for MCL  PubMed
bullet

Radioimmunotherapy:

bullet
Radioimmunotherapy Consolidation in Mantle Cell Lymphoma http://bit.ly/9kt6WK PDF http://bit.ly/c7HIxm 

Wojciech Jurczak, European Oncological Disease - Published: October 2008
 
A thorough description of the rationale for consolidation with RIT for MCL – but also informative for other lymphomas.
bullet
High-Dose Iodine-131-Labeled Rituxan and Autologous Stem Cell Support Produces Long Lasting Effects in Patients with Mantle Cell Lymphoma Failing Conventional Autologous Transplants  cancerconsultants.com 

Also see full text:  bloodjournal.hematologylibrary.org
bullet
Zevalin in Mantle Cell Lymphoma touchbriefings.com   pdf  

Conclusion: Radiotherapy is an active treatment modality in MCL. Ibritumomab radioimmunotherapy (Zevalin) is an interesting alternative to other consolidation methods. In younger patients subjected to intensive chemotherapy followed by autologous transplant, it may be an element of a transplant conditioning regimen (i.e. Z-BEAM). In elderly patients, the role of zevalin consolidation should be further investigated in a phase III trial.
bullet
Studies presented at ASH explore activity of the Bexxar® therapeutic regimen in difficult-to-treat lymphomas  www.icaa.eu
bullet

Targeted / Immune-based Therapy:

bullet
Lenalidomide (Revlimid) Oral Monotherapy in Patients with Mantle
Cell Lymphoma Previously Treated with Bortezomib (Velcade) http://bit.ly/VandR
bullet
Revlimid® Active for Treating Mantle Cell Lymphoma cancerconsultants.com

n = 15 patients with mantle cell lymphoma who had failed prior therapy, including stem cell transplantation in five. 

The overall response rate was 53% with 20% (n=3) having a complete response. The median duration of response was 14 months, and the median progression-free survival was 5.6 months. Four of the five patients who had failed stem cell transplantation responded.
bullet
Temsirolimus (mTOR inhibitor) Promising for Treatment of MCL and other cancers  cancerconsultants.com
 
bullet
Managing and avoiding bortezomib (Velcade) toxicity 
Jeffrey Menashe, MD | Northwest Cancer Specialists, Portland, OR
 communityoncology.net pdf
bullet
Response to thalidomide in chemotherapy-resistant mantle cell lymphoma: a case report. Br J Haematol. 2002 Oct;119(1):128-30. PMID: 12358916  PubMed
bullet
Phase II Trial of Single-Agent Temsirolimus (CCI-779) for Relapsed Mantle Cell Lymphoma. J Clin Oncol. 2005 Jun 27  PMID: 15983389
bullet
A low toxicity maintenance regime, using eicosapentaenoic acid and readily available drugs, for mantle cell lymphoma and other malignancies with excess cyclin D1 levels. Med Hypotheses. 2003 May;60(5):615-23. PMID: 12710892  PubMed
bullet
Velcade: Inhibition of the proteasome induces cell cycle arrest and apoptosis in mantle cell lymphoma cells. Br J Haematol. 2003 Jul;122(2):260-8. PMID: 12846895  PubMed
bullet

Combination therapy:

bullet
Phase II multicenter study of bendamustine plus Rituxan in patients with relapsed indolent B-cell and mantle cell NHL.  
J Clin Oncol. 2008 Sep 20;26(27):4473-9. Epub 2008 Jul 14. PMID: 18626004  

(n = 66 patients with relapsed, indolent B-cell or mantle cell lymphoma (without documented resistance to prior rituximab)

Overall response rate was 92% (41% complete response, 14% unconfirmed complete response, and 38% partial response). Median duration of response was 21 months (95% CI, 18 to 24 months). Median progression-free survival time was 23 months (95% CI, 20 to 26 months). Outcomes were similar for patients with indolent or mantle cell histologies.
bullet
Fludarabine-based chemotherapy in untreated mantle cell lymphomas:
an encouraging experience in 29 patients PIER LUIGI ZINZANI et al. - Haematologica 1999; 84:1002-1006 PDF

Other Treatment-related items:

bullet
Standard Therapy for Mantle Cell Lymphoma? http://bit.ly/htWQpf
bullet
Ki-67 as a prognostic marker in MCL—consensus guidelines of the pathology panel of the European MCL Network ncbi.nlm.nih.gov
bullet
RQ-PCR Positivity Predicts Relapse of Mantle Cell Lymphoma 
after Autologous Stem Cell Transplant  cancerconsultants.com

The researchers concluded that the presence of MRD (minimal residual disease) following an AutoSCT in patients with MCL is highly predictive of outcomes in this group of patients. The authors suggest testing for MRD in this group of patients; those with MRD may benefit from additional or more aggressive therapies.
bullet
Mantle Cell treatment effective  BBCNews  
bullet
Mantle cell lymphoma involving skin: cutaneous lesions may be the first manifestation of disease and tumors often have blastoid cytologic features. Am J Surg Pathol. 2002 Oct;26(10):1312-8. PMID: 12360046  PubMed
Clinical Trials
Return to top

ClinicalTrials.gov

bullet
All studies
bullet
Newly Diagnosed or untreated 
bullet
Recurrent
bullet
Excluding stem cell transplant (by request)
bullet
Treatment type
bullet
State or Country
bullet
Other criteria such as age, stage, phase, refractory
Research News
Return to top

Research News

bullet
The Mantle Cell Lymphoma Prognostic Index (MIPI) Superior to IPI http://bit.ly/5UsntE | Full
bullet
A new prognostic index (MIPI) for patients with advanced stage mantle cell lymphoma. Blood. 2007 Oct 25  PMID: 17962512

According to the MIPI, patients were classified into low risk (44% of patients, median OS not reached), intermediate risk (35%, 51 months), and high risk groups (21%, 29 months), based on the four independent prognostic factors: (1) age,  (2) ECOG performance status, (3) LDH and leukocyte count. 
bullet
Ki-67 as a prognostic marker in MCL—consensus guidelines of the pathology panel of the European MCL Network ncbi.nlm.nih.gov
bullet
High Rate of Durable Remissions After Treatment of Newly Diagnosed Aggressive Mantle-Cell Lymphoma With Rituximab Plus Hyper-CVAD Alternating With Rituximab Plus High-Dose Methotrexate and Cytarabine.  ASCO 2005
bullet
Mantle cell lymphoma: prognostic capacity of the 
Follicular Lymphoma International Prognostic Index (FLIPI).
Br J Haematol. 2006 Apr;133(1):43-9. PMID: 16512827 | See FLIPI
bullet
Allogeneic stem cell transplantation for mantle cell lymphoma--does it deserve a better look? Leuk Lymphoma. 2005 Feb;46(2):217-23. PMID: 15621804
bullet
The Leukemic Presentation of Mantle-cell Lymphoma: Disease Features and Prognostic Factors in 58 Patients. Leuk Lymphoma. 2004;45(10):2007-2015. PMID: 15370245   

"This analysis demonstrates that except for splenomegaly, survival of MCL patients presenting with leukemia is not significantly influenced by clinical or tumor characteristics. Splenectomy is a useful treatment option in this group of patients."
bullet
Allogeneic “Mini” Stem Cell Transplant Effective for Recurrent Mantle Cell Lymphoma  cancerconsultants.com
bullet
Long-term follow-up of autologous stem cell transplantation in patients with diffuse mantle cell lymphoma in first disease remission: the prognostic value of beta2-microglobulin and the tumor score. Cancer. 2003 Dec 15;98(12):2630-5. 
PMID: 14669282 | Related articles
bullet
Survivin Expression in Mantle Cell Lymphoma I ... The role of survivin in the pathogenesis of mantle cell lymphoma (MCL) was examined in a series of typical and blastoid tumors. amjpathol.org 
 
Disclaimer:  The information on Lymphomation.org is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns,  you should always consult your doctor. 
Patients Against Lymphoma, Copyright © 2004,  All Rights Reserved.