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Types of Lymphoma >
Mantle Cell Lymphoma
(MCL)
Last update:
05/25/2010
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TOPICS:
Overview
| Treatments | Clinical
Trials | Prognosis
& Response to Treatment
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About
Lymphomas
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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 Image
of Marginal Zone b-lymphocytes
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
See for details e-medicine
Common symptoms
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fatigue (anemia) |
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loss of appetite |
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feeling of fullness or discomfort due to enlarged
liver or spleen |
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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
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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.
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Non-Hodgkins Lymphomas - Clinical Practice
Guidelines in Oncology
nccn.org
professionals pdf (one-time free registration and login
required) |
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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."
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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.
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Variants:
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H. A. Leitch1, R. D. Gascoyne2, M. Chhanabhai2, N. J. Voss3,
R. Klasa1 and J. M. Connors |
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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. |
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Treatments
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Treatment Articles
TOPIC SEARCH
PubMed: Review
| Therapies
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Stem
Cell Transplant
ASCO | Medscape
| FDA
| WEB
New Agents/Protocols: Velcade
| Targeted
| Revlimid
| mTOR inhibitors
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:
(1) the discovery of defects in MCL that can be targeted by new agents, such as mTOR inhibitors and Velcade, (2) the sometimes remarkable activity of immune modulating agents such as Revlimid in MCL,
(3) the potential of radioimmunotherapy consolidation to improve on outcomes, and
(4) recent data from the Nordic group regarding stem cell transplant following ARA-C based chemotherapy - which seems to show curative
potential
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.
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Overview on Treatment of MCL:
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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."
~ New directions in the treatment of mantle cell lymphoma: an
overview. Clin Lymphoma Myeloma. 2006 Oct;7 Suppl 1:S24-32. PMID:
17101070 | Related
articles
~ Mantle
Cell Lymphoma: At Last, Some Hope for Successful Innovative
Treatment
Strategies ~ Editorial by Dr. Richard I. Fisher jco.org
~ MCL - Treatment policy prepared by Dr. Kevin
Imrie - Updated Feb 2003: minor changes on rituximab tsrcc.on.ca
- PDF
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Stem cell transplant:
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ARA-C
incorporation into SCT (Nordic group)
Protocol
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Reports
click to enlarge
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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) |
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~ 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
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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. |
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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 |
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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
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The Role of Autologous Transplantation in the Management of Mantle Cell Lymphoma:
A Study From the EBMT E. Vandenberghe, C. Ruiz de Elvira, P. Isaacson, E. Lopez-Guillermo, E.
Conde, C. Gisselbrecht, F. Guilhot, A. Goldstone, N. Schmitz
PDF
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" Mini " Transplants Effective in Recurrent Mantle
Cell cancerconsultants.com
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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
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Hyper CVAD Followed by SCT for MCL
PubMed
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Radioimmunotherapy:
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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.
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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
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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.
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Studies presented at ASH explore activity of the Bexxar® therapeutic regimen in difficult-to-treat lymphomas
www.icaa.eu
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Targeted / Immune-based Therapy:
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Lenalidomide (Revlimid) Oral Monotherapy
in Patients with Mantle
Cell Lymphoma Previously Treated with Bortezomib (Velcade)
http://bit.ly/VandR
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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.
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Temsirolimus (mTOR inhibitor) Promising for Treatment of MCL
and other cancers
cancerconsultants.com
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Managing and avoiding
bortezomib (Velcade) toxicity
Jeffrey Menashe, MD | Northwest Cancer Specialists, Portland, OR
communityoncology.net
pdf |
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Response to thalidomide in chemotherapy-resistant
mantle cell lymphoma: a case report. Br J Haematol. 2002
Oct;119(1):128-30. PMID: 12358916
PubMed
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Phase
II Trial of Single-Agent Temsirolimus (CCI-779) for Relapsed
Mantle Cell Lymphoma. J Clin Oncol. 2005 Jun 27
PMID:
15983389 |
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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
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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
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Combination therapy:
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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. |
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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
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Other Treatment-related items:
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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.
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Mantle Cell treatment effective BBCNews
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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
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Clinical Trials
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ClinicalTrials.gov
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Prognosis &
Response to
Treatment
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Prognosis & Response to
Treatment
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The Mantle Cell
Lymphoma Prognostic Index (MIPI) Superior to IPI
http://bit.ly/5UsntE |
Full
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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.
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Cell proliferation (Ki-67) was exploratively analyzed as
important biological marker and showed strong additional
prognostic relevance. |
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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 |
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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
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Allogeneic stem cell transplantation for mantle cell
lymphoma--does it deserve a better look? Leuk Lymphoma. 2005
Feb;46(2):217-23.
PMID:
15621804 |
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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." |
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Allogeneic “Mini” Stem Cell Transplant Effective for
Recurrent Mantle Cell Lymphoma
cancerconsultants.com
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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 |
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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
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