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About
Lymphoma > Types of Lymphoma > Follicular (Center
Cell) Lymphoma
Last update:
03/14/2010
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TOPICS
Overview
| Subtypes | Grade 3 |
Cutaneous
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Treatment & Clinical
Trials | Research News
TOPIC SEARCH: PubMed: Diagnosis
| Review
| Therapies
| Prognosis |
Refractory
Therapies: ASCO |
Medscape
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ABOUT
Lymphomas
Lymphomas versus "solid" cancers
It's
common to be diagnosed with lymphoma at an advanced stage (III or IV)
and with bone marrow involvement. While this might seem alarming, you should know that advanced stages
of lymphoma can be treated successfully, and that lymphoma in the bone
marrow is as reversible as lymphoma anywhere in the body.
One way to understand this is to compare lymphoma with a so-called
solid tumor, such as a prostate cancer. Here the cell of origin
does not normally exist anywhere but in the prostate. So when
you find malignant prostate cells in the lymph nodes, or in the bone
marrow, you have a big problem. Compare with blood cells that we
expect to move anywhere in the lymphatic or circulatory system,
including the nursery for these cells, the bone marrow.
Another favorable aspect of blood cancers is that they are generally
much more sensitive to treatment than "solid" tumors,
probably because blood cells are more poised to self- destruct, and
they can also regenerate more readily from stem cells in the marrow.
Consider that the main side effect of chemotherapies is a drop in
blood counts, but not the destruction of normal prostate or breast
cells ...
We're
not suggesting that lymphoma is not a life-threatening disease.
It is. But we know that many types of lymphomas can be managed
well, other types can be cured, and the potential to make additional
progress against this family of diseases is real.
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Follicular
(center cell) non-Hodgkin's Lymphoma is a
b-cell cancer - a b-cell is type of lymphocytes or
white blood cell that normally defends you against bacteria and other
types of pathogens that cause illness.
"Follicular" describes the cell
type. B-cells arise from the bone marrow and mature or
differentiate into many cell types that migrate to different
areas of the body. Normal follicular b-cells reside in the
germinal center of lymph nodes. The majority of follicular
lymphoma have an indolent (slow growing) clinical course.
B-cell stage: mature, after antigen exposure
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What is lymphoma?
Lymphomas result when damage
to DNA occurs to a type of white blood cell (a lymphocyte)
that results in the
abnormal production of proteins that prevents the cells from dying when
they should, or causes sustained rapid cell division.
These malignant cells
then may accumulate to form tumors that may enlarge the lymph nodes or
spread to other areas of the lymphatic
system, such as the spleen or
bone marrow.
Lymphoma cells can also migrate to, or first appear, outside the
lymphatic system. Lymphoma that presents outside the lymphatic
system is called extranodal
disease. For details, see Lymphoma simplified.
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Incidence
Follicular non-Hodgkin's Lymphoma (NHL) is a very common type of b-cell lymphoma, comprising
approximately 30% of all cases. There are about 61,000 new cases of
NHL diagnosed annually. Therefore, there are approximately 18,300 new
cases of follicular NHL diagnosed annually. Follicular lymphomas
account for 70% of indolent (slow growing) lymphomas. The mean
age at diagnosis is about 60 to 65 years.
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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.
Resources:
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Staging
Staging
refers to the how widespread the disease is. Imaging
tests (CT MRI, PET, Gallium) and bone marrow biopsies are commonly
done to estimate this. See Staging for
more detail.
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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.
Prognostic indicators
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The variable natural history
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Indolent
grade
"Follicular lymphomas are characterized by relatively
long median survivals and a continuous pattern of relapse. The
heterogeneity (variable clinical courses) in these diseases is
increasingly appreciated, leading to concerted efforts to
define prognostic factors and risk-adapted strategies."
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FLIPI Follicular Lymphoma
International Prognostic Index
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Resources
| NEW
Clinical Features, Prognosis and Treatment of Follicular Lymphoma
Gilles Andre Salles, MD, PhD, Centre Hospitalier Lyon-Sud, 165, Ch
du Grand Revoyet, asheducationbook.hematologylibrary.org
2007
The therapeutic strategies in follicular
lymphoma have been transformed by monoclonal
antibodies, used alone or in combination with chemotherapy.
Treatment options should be adapted to the clinical features
at diagnosis and appear to be able to modify the overall survival
of some subgroups of patients. Further efforts may focus
on strategies that can alter the natural history of this disease.
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| Aiming at a Curative Strategy for Follicular Lymphoma
caonline.amcancersoc.org Maurizio Bendandi,MD, PhD
One clear fact is that no patients will ever be cured by adopting a palliative treatment approach. The assumption that patients with follicular lymphoma are incurable is certain to be a
self-fulfilling prophecy. Here the author summarizes the large and growing body of knowledge that suggests an expectant approach to management is not appropriate for all patients. (CA Cancer J Clin 2008;58:305–317.) © American Cancer Society, Inc., 2008.
http://caonline.amcancersoc.org:80/cgi/reprint/58/5/305?eaf
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Evolving Paradigms in Follicular Lymphoma: Re-Evaluating
Prognostic Factors and Challenging Treatment Dogmas molecularonc.com
Cara A. Rosenbaum, MD
Current clinical indices and molecular markers in follicular
lymphoma must be re-evaluated and incorporated actively into
prospective trials to allow development of risk-adapted treatment
guidelines and novel targeted therapies. The results of such
studies will help to further recommendations regarding the
effective timing of therapeutic intervention (ie, watchful waiting
versus active treatment) and the efficacy of various
chemotherapeutic regimens in different patient populations.
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| Non-Hodgkins Lymphomas Clinical Practice
Guidelines in Oncology – v.1.2006 nccn.org
pdf
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| Low grade Lymphoma asheducationbook.org
/2004 full text |
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Subtypes of Follicular Lymphoma
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Subtypes of Follicular non-Hodgkin's lymphomas
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Follicular
lymphomas are further categorized by cell
size: "The cells of follicle center
lymphomas are derived from the germinal center cells of the
normal lymph node. This category in the Working Formulation
encompasses three different tumor types:
follicular predominantly small-cleaved
(generally slower growing),
follicular mixed small-cleaved and large-cell, and
follicular predominantly large-cell (generally faster
growing).
In the Kiel classification, these tumors
are included within the centroblastic/centrocytic and
follicular centroblastic classifications."
source: cancernetwork
[1375] Extranodal Follicular Lymphoma - a
Retrospective Review and Comparison with Localized Nodal
Follicular Lymphoma. Session Type: Poster Session 529-I - ASH
2004 | Terms
of Use
Predictive
signatures came from immune cells:
"
Two signatures [in follicular lymphomas] -- one which indicated poor
prognosis, the other good--had strong synergy and together predicted
survival better than any other model tested.
Unexpectedly, both came
from nonmalignant immune cells infiltrating the tumors. The good
prognosis signature genes reflect a mixture of immune cells that is
dominated by T cells. T cells react to specific threats to the
body's health. In contrast, the poor prognosis signature genes
reflect a different group of immune cells dominated by macrophages
and/or dendritic cells--which react to nonspecific threats--rather
than T cells.
http://www.cancer.gov/
Also see Host/tumor
interaction and the microenvironment
See more on each
subtype below.
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Follicular
Large-Cell
(Grade 3)
As tumor classification systems evolve, research using older systems may show different results
than newer systems. As insights into genetic and molecular aspects of
tumors are discovered it is hoped that treatment strategies more
tailored to an individual's tumor will be identified. This will take
research and will be facilitated by participation in research trials.
- Anjou NHL-info
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Follicular Large-Cell (Grade 3)
 TOPIC
SEARCH: Ash-Education
| PubMed
Grade 3 Follicular lymphomas make up only a minority
of all Follicular lymphomas.
Follicular
Large cell lymphomas may have a more aggressive clinical behavior, and
therefore treatments may be initiated early with intend to cure or
produce durable remissions.
Grade 3
confusion:
"The WHO classification system recommends separating FL
(follicular lymphoma) into three different grades according to the
number of centroblasts per high-power field:
| grade 1
(<5 centroblasts/hpf)
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grade 2
(5-10 centroblasts/hpf)
Grade 1 and 2 are now considered the same entity
(observed and treated the same) |
| grade 3
(>15 centroblasts/hpf) (large cell) |
"Also, it is recommended that in
addition to a grade the biopsy be scored for the amount of
diffuse
component present. The clinical importance of grade and
diffuseness are unclear and generate much debate." ~ Halaas, et.
al. (ASH
2003 - abstract)
Resources and Reports:
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NEW
Gene expression analysis provides a potential rationale for revising
the histological grading of follicular lymphomas, May 2008
http://www.haematologica.org/cgi/content/full/93/7/1033
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Non-Hodgkins Lymphomas
Clinical Practice
Guidelines in Oncology – v.1.2006
nccn.org
professionals pdf |
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Low-Grade Lymphoma, Hematology 2004
asheducationbooks
Jane N. Winter, Randy D. Gascoyne and Koen Van Besien
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Cytologic subtypes of grade 3 follicular lymphoma
bloodjournal.hematologylibrary.org
The authors conclude that the 3a-3b distinction does not
correlate with response to treatment or with clinical
outcome. But the presence and extent of a diffuse
large-cell component does correlate with behavior of
the disease. The latter finding appears to justify the
WHO-sanctioned practice of rendering a separate diagnosis
of
diffuse large B-cell lymphoma in such cases.
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| Patients with grade 3 follicular lymphoma have prolonged
relapse-free survival following anthracycline-based chemotherapy:
the Nebraska Lymphoma Study Group Experience.
Ann Oncol. 2006 Jun;17(6):920-7. Epub 2006 Mar 8. PMID:
16524969 Full
text
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Follicular Lymphoma grade 3B. A
separate entity?
dissertations.ub.rug.nl
Bosga-Bouwer, Annigje Geesje (Technical) |
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Natural history of follicular grade 3
non-Hodgkin's lymphoma. Bierman PJ. Curr Opin Oncol. 2007
Sep;19(5):433-7.
Review
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Reports
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A Clinicopathologic Evaluation of Follicular Lymphoma
Grade 3A Versus Grade 3B Reveals No Survival Differences http://findarticles.com
In summary, we present a series of pure FL grade 3.
Subtyping into FL grades 3A and 3B subtypes, as proposed by the
WHO classification, did not appear to be useful as a prognostic
factor for overall survival. Previous lower grade FL or treatment
with anthracycline-containing regimens did not appear to confound
the analysis. Despite our findings, it may be that important
biologic differences between these subtypes exist. Since
morphologic clues often provide leads for further investigation,
it is premature to argue against the continued practice of
subtyping. Further characterization of such cases at the genetic
and protein-expression levels may yield clinically important
factors that do predict outcome.
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A significant diffuse
component predicts for inferior survival in grade 3
follicular lymphoma, but cytologic subtypes do not predict
survival.
Blood. 2003 Mar 15;101(6):2363-7. Epub 2002 Nov 07. PMID: 12424193
full
text | related abstracts
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PubMed abstracts for Large cell follicular:
Review
| Therapy
| Diagnosis
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Follicular Large Cell Lymphoma: An Aggressive Lymphoma That
Often Presents With Favorable Prognostic Features bloodjournal.org
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Grade
3 and anthracycline-containing treatments [such as CHOP]
Commentary from Experts PAL
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Follicular
Mixed-Cell
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It's common to find a mix of cell-sizes in the
diagnosis of follicular lymphoma.
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Follicular
Small-Cell/
Cleaved
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Most
common cell-size subtype of follicular lymphoma. An indolent (slow
growing) lymphoma.
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Cutaneous - skin
(extranodal)
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Sometimes
follicular lymphomas are first diagnosed in the skin (present
there), or spread to the skin later on. When lymphomas
that normally present in the lymphatic system moves to other areas it
is called extranodal disease. Spreading to the skin is not
necessarily considered a negative prognostic indicator.
Also see Extranodal
lymphomas
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Follicular Center Cell Lymphomas of the Skin thedoctorsdoctor.com
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Cutaneous follicle center lymphoma: a
clinicopathologic study of 19 cases.
Mod Pathol. 2001 Sep;14(9):828-35. PMID: 11557777 PubMed
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Cutaneous presentation of follicular lymphomas.
Mod Pathol. 2001 Sep;14(9):913-9. PMID: 11557789 PubMed
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Treatments
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Treatments
Also
see
Questions for your doctor - Patients
Against Lymphoma
General, Treatment, Side Effects, and Tests
Factors that determine
treatment timing and approach:
The characteristics of the lymphoma at
diagnosis as determined by the pathology report, and it's actual
clinical behavior, and other factors determine the type of treatment
and the timing of treatment you and your doctor will consider.
The
good news is that lymphomas are often sensitive and responsive to
treatments. Aggressive lymphoma are often cured, and indolent (slow
growing) lymphomas are often managed effectively. Importantly, recent
advances in the understanding of lymphoma has led to effective new
therapies and better therapies are certain to follow.
For indolent lymphomas, treatment is often deferred
until the patient becomes symptomatic. For aggressive lymphomas
treatment is typically initiated early with intent to cure.
| See Factors that influence treatment selection
and timing - PAL
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There is no apparent standard treatment for
indolent follicular lymphomas.
Current practices include:
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Watchful waiting until symptoms, marked
progression, or transformation occurs, |
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Management with single agent chemotherapy and/or
Rituxan when needed. |
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Numerous Investigational therapies. See below. |
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Aggressive early treatments with combination
therapies for high-risk disease, such as when the lymphoma is
resistant to initial treatments. |
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Radioimmunotherapy,
with Zevalin or Bexxar |
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Stem cell transplants,
ablative and mini (non-ablative). |
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Radiotherapy, which may cure if treated when in
stage I or II |
TOPIC
SEARCH: PubMed: Review
| Therapies
ASCO
| Medscape
| FDA
|
Web
General Guidelines for Indolent Lymphomas:
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Adult Non-Hodgkin’s Lymphoma ~ Best Practice Cancer.gov
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| Considerations at Relapse PAL
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| Treatment decisions - factors that determine
PAL
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Watchful waiting PAL
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| Elderly ~ treatments for PAL
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| Refractory (resistant to treatment) resource page
PAL
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Transformed disease PAL
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Related News and Resources
| NEW: R-CHOP versus R-CVP in the treatment of follicular lymphoma: a meta-analysis and critical appraisal of current literature
pubmedcentral.nih.gov
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| Aiming at a Curative Strategy for Follicular Lymphoma
caonline.amcancersoc.org
Maurizio Bendandi,MD, PhD
One clear fact is that no patients will ever be cured by adopting a palliative treatment approach. The assumption that patients with follicular lymphoma are incurable is certain to be a
self-fulfilling prophecy. Here the author summarizes the large and growing body of knowledge that suggests an expectant approach to management is not appropriate for all patients. (CA Cancer J Clin 2008;58:305–317.) © American Cancer Society, Inc., 2008.
http://caonline.amcancersoc.org:80/cgi/reprint/58/5/305?eaf
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| Cure for fNHL? Radiolabeled and
Native Antibodies and the Prospect of Cure of Follicular Lymphoma theoncologist.alphamedpress.org
"In this review, we hypothesize that the combination of
an optimized biological treatment together with radiolabeled antibodies
and chemotherapy early in the disease course of advanced-stage
follicular lymphoma may represent the best approach to
achieve prolonged disease-free survival and eventually
cure."
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| Cure word used: Mini-BMT:
follicular Non-Hodgkin's Lymphoma Cure? www.webmd.com
83% in Complete Remission 5 to 9 Years After Mini-BMT for
Follicular Lymphoma
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| Stage I and II Follicular Non-Hodgkin’s
Lymphoma: Long-Term Follow-Up of No Initial Therapy ~ Ranjana
Advani, Saul A. Rosenberg, Sandra J. Horning 2004 - full text
article jco.org
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| Treatment of Non-Hodgkin's Lymphoma: Next Steps
- Medscape.com
2004 (free login req.) Review of progress for Follicular, SLL,
Diffuse Large Cell, and Mantle Cell.
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| Follicular Lymphoma, Treatment Policy - Dr.
Louise Bordeleau PDF
| PDF-Help
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| Treatment overview PAL
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ClinicalTrials.gov (easy and
comprehensive) searches by
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Research News
TOPIC
SEARCH: WebNews |
Research News
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| Technical:
Atlas of Genetics and Cytogenetics in Oncology and Haematology -
Follicular lymphoma http://bit.ly/8LTric
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Molecular pathways in follicular lymphoma nature.com
pdf
RJ Bende, LA Smit and CJM van Noesel, Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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| Survival
Improving for Patients with Stage IV Follicular Lymphoma cancerconsultants.com
Researchers from the M.D. Anderson Cancer Center have reported
that overall survival and failure-free survival of patients with
stage IV follicular non-Hodgkin’s lymphoma (NHL) has
significantly improved between 1972 and 2002. The details of this
study appeared in the April 1, 2006, issue of the Journal of
Clinical Oncology.
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Bcl-2 negative: Follicular center cell lymphoma with the
t(14;18) translocation in which the rearranged BCL-2 gene is
silent. Leukemia. 1993 Nov;7(11):1834-9.
PMID: 7694006 PubMed
| Related
Abstracts
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Low-grade stage III-IV follicular lymphoma: multivariate
analysis of prognostic factors in 484 patients--a study of the
groupe d'Etude des lymphomes de l'Adulte.
J Clin Oncol. 1999 Aug;17(8):2499-505. PMID: 10561315 PubMed
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Clinicopathologic
correlations of genomic gains and losses in follicular lymphoma.
J Clin Oncol. 2002 Dec 1;20(23):4523-30. PMID: 12454108 PubMed
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Interferon in Oncological Practice: Review of Interferon Biology, Clinical Applications, and Toxicities
Eric Jonasch, Frank G. Haluska Massachusetts General Hospital, Boston, Massachusetts, USA
alphamedpress.org
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Combined therapy in advanced stages (III and IV) of
follicular lymphoma increases the possibility of cure: results of
a large controlled clinical trial. Eur J Haematol. 2002
Mar;68(3):144-9. PMID: 12068794 PubMed
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High-Dose Therapy for Follicular Lymphoma Oncology
Arnold Freedman, MD, Jonathan W. Friedberg, MD , and John Gribben, MD, PhD
Department of Medicine, Harvard Medical
School, Dana-Farber Cancer Institute, Boston, Massachusetts
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Prolonged single-agent versus combination chemotherapy in
indolent follicular lymphomas: a study of the cancer and leukemia
group B.
J Clin Oncol. 2003 Jan 1;21(1):5-15. PMID: 12506163 PubMed
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New Treatment Options Have Changed the Survival of
Patients With Follicular Lymphoma. J Clin Oncol. 2005 Oct 17; PMID:
16230674 | Related
articles
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