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About
Lymphoma > Prognostic Indicators
Last update: 04/25/2008
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Prognostic
Indicators & Biomarkers | IPI | FLIPI
Indications to treat Follicular NHL: GELF / NCCN
Specific Biomarkers
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Prognostic
Indicators
TOPIC
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Related Topics:
Diagnosis
& Pathology
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Pathology Evaluation
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indicators
Performance
Standards
Diagnostic
Tests
Disease
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Microenvironment
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Prognostics TOPIC
SEARCH
ASCO.org
| ASH
| Medscape |
PubMed
"Because most of the
prognostic studies are based on a retrospective analysis of historical
data, they must be interpreted with caution at a time when treatment
modalities are changing." herkules.oul
Question: I have been diagnosed with Lymphoma Stage 4. Do you have
any statistics as to the survival rate of patients with this
diagnosis?
Answer:
Survival of lymphoma depends on the cell type ... there are about 30
types of lymphoma. Some types of lymphoma can be cured.
Other cell types can be managed very well, like a chronic
disease.
Survival statistics are calculations applied to large groups, which
show averages. Therefore statistics cannot predict what will happen
to you or a loved one. Each patient and case is unique, and treatment
outcomes can vary from one person to another. Indeed, not even
your doctor can tell you for sure what will happen.
The term
'5 year survival' is used often. It relates to the proportion
of people in research studies who were still alive 5 years after
diagnosis. However, importantly, patients who live 6, 10, or 30 years after
diagnosis are also in this group.
Therefore "5 year survival" statistics do not mean
you have five years to live!
What is more, the survival expectations can increase
for those who have survived beyond 1, 2, 3, or 4 years. For
example, 8 year survival might be the average for a given type of
lymphoma, but for patients who have already survived five years, the
average survival could be well beyond the average survival at
diagnosis.
Furthermore, Overall Survival (OS) is calculated
based on death from any cause, and is strongly influenced by the
average age at diagnosis. For follicular lymphomas, a median OS of 8
to 10 years is often cited and the average age at diagnosis is about
65 years. However, a recent report from Stanford, based on patients
with a median age of 49, the median (average) OS was 18 years.
Factors that influence, but do not predict, the survival for
patients with lymphoma include:
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the cell
type, |
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the grade
(a good percentage of pts with aggressive NHL can be cured, and
pts with indolent NHL can live well and long with the disease) |
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the stage of the
disease (almost everyone is diagnosed with stage 4), |
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the age and
performance level of the patient, |
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tumor
burden, |
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LDH
levels, |
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number of extranodal
sites (tumors outside the lymph organs). |
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hemoglobin level (< 12
g/dL vs. >/= 12 g/dL), |
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response to initial treatment, and duration of the response;
"Response to treatment is one of the most important prognostic
indicators, particularly in patients with aggressive NHL."
ncbi.nlm.nih.gov |
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and genetic characterizations,
including the microenvironment
that are now being
discovered with advanced testing. |
Resources:
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Expert background: Optimal Use of
Prognostic Factors in NHL asheducationbook.
2006 pdf
The management of non-Hodgkin lymphoma is complicated by wide
heterogeneity within recognized subtypes. Patients with supposedly
similar diagnoses can have remarkably varied clinical
presentations, molecular profiles and clinical outcomes. Reliable
prognostic markers could allow the identification of patient
subsets that may benefit from alternate approaches.
|
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Survival after progression in patients with follicular
lymphoma: analysis of prognostic factors annonc.oxfordjournals.org
In patients with FL, Response Duration (RD) along with performance
status at progression are features that predict
Survival Following Progression. These variables could thus be
useful to select candidates
for experimental treatments.
|
| cFLIP expression correlates with tumour progression and
patient outcome in non-Hodgkin lymphomas of low grade of
malignancy. Br J Haematol. 2006 Mar;132(5):560-70. PMID:
16445828
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|
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| Ann Arbor Stages of
Non-Hodgkin's Lymphoma Grade
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| Biologic Prognostic Features in Non-Hodgkin’s Lymphoma and Their Implications, Bertrand Coiffier
PDF | PDF-Help
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| Bone marrow involvement and survival for low grade NHL?
PubMed
| Related
articles
"Conclusion. The presence of bone marrow infiltration at
diagnosis did not significantly affect the prognosis of LGNHL."
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| Liver involvement and survival? PMID: 10561315 PubMed
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| Transformation PAL
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| What if I'm BCL2 negative? BCL2
Negative
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Research News
Diffuse Large Cell Lymphoma:
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Is it time to stop treating subsets of DLBCL with R-CHOP?,
Craig Moskowitz (MSKCC) bloodjournal.org
full
"Diffuse large B-cell lymphoma (DLBCL) is markedly
heterogeneous morphologically, clinically, and
genetically. With the application of gene expression
profiling analyses, DLBCL has evolved into at least 2
entities: germinal center B (GCB)–cell and an
activated peripheral blood B-cell (ABC) lymphoma.1"
|
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A redox signature score identifies diffuse large B-cell lymphoma patients with a poor
prognosis.Blood. 2005 Aug 4; PMID: 16081686
| Related
articles
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Follicular lymphoma:
TOPIC SEARCH microenvironment WEB
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Gene-Expression and Immunohistochemical Study of Specific
T-Cell Subsets and Accessory Cell Types in the Transformation and
Prognosis of Follicular Lymphoma. J Clin Oncol. 2007 Jan 2; PMID:
17200149 | Related
articles
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| Overexpression of SOCS3 is associated with decreased
survival in a cohort of patients with de novo follicular lymphoma.
Br J Haematol. 2006 Aug 24; PMID:
16939500
OCS3-positive FL patients had a median OS of 10 years compared
with 22 years in
SOCS3-negative patients (P = 0.001, log rank test).
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| Immunohistochemical analysis of the antiapoptotic Mcl-1 and
Bcl-2 proteins in follicular lymphoma. Br J Haematol. 2006
Mar;132(6):743-6. PMID:
16487175
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| Molecular pathogenesis of follicular lymphoma: a cross talk
of genetic and immunologic factors. J Clin Oncol. 2005 Sep
10;23(26):6358-63. Review. PMID:
16155020
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| Increased Vascularization Predicts Favorable Outcome in
Follicular Lymphoma 2005 aacrjournals.org |
full
text
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| Predicting Cancer Patient Survival with Gene Expression Data
DOI: 10.1371/journal.pbio.0020118 - full text plosbiology.org
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| [2266] Follicular Lymphoma: Design of a
Protein-Based Survival Predictor Using Tissue-Microarrays (TMA).
Session Type: Poster Session 479-II ASH
2004
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High expression of cyclin B1 predicts a favorable outcome of
patients with follicular lymphoma. Blood. 2004 Dec 2; PMID:
15576476
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Bone marrow histological patterns can predict survival of
patients with grade 1 or 2 follicular lymphoma: a study from the
Groupe d'Etude des Lymphomes Folliculaires.
Br J Haematol. 2004 Aug;126(3):364-71. PMID:
15257708
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Follicular lymphoma international prognostic index.
Blood. 2004 May 4 [Epub ahead of print] PMID:
15126323
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Prognostic indicator:
Expression of bcl-6 and CD10 protein is associated with longer
overall survival and time to treatment failure in follicular
lymphoma. Am J Clin Pathol. 2004 Jan;121(1):34-42. PMID:
14750238 | Related
articles
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Prognosis of
follicular lymphoma: a predictive model based on a retrospective
analysis of 987 cases. Intergruppo Italiano Linfomi. Blood. 2000
Feb 1;95(3):783-9 full
text | Related
abstracts
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Survival in young patients (less than 40 years) with
follicular lymphoma: a population based study by the Scotland and
Newcastle Lymphoma Group. Leuk Lymphoma. 2004 Jun;45(6):1149-57. PMID:
15359994
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Survival after progression in patients with follicular
lymphoma: analysis of prognostic factors. Ann Oncol. 2002
Apr;13(4):523-30. PMID:
12056701 | Related
articles
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Serum CA 125 as a
prognostic factor in non-Hodgkin's lymphoma.
Leuk Lymphoma. 2003 Oct;44(10):1733-8. PMID:
14692526 | Related
articles
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| High serum
interleukin-6 levels correlate with a shorter failure-free
survival in indolent lymphoma. Leuk Lymphoma. 1998
Aug;30(5-6):563-71. PMID:
9711918 | Related
articles
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| Increased serum
levels of interleukin-9 correlate to negative prognostic factors
in Hodgkin's lymphoma. Leukemia. 2003 Oct 9 [Epub ahead of print] PMID:
14562126 | Related
articles
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| Presentation serum
selenium predicts for overall survival, dose delivery, and first
treatment response in aggressive non-Hodgkin's lymphoma. J Clin
Oncol. 2003 Jun 15;21(12):2335-41. PMID: 12805335
| Related
articles
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Tumor load in patients
with follicular lymphoma post stem cell transplantation may
correlate with clinical course. Bone Marrow Transplant. 2003
Aug;32(3):287-291. PMID: 12858200 PubMed
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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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A significant diffuse component predicts for inferior survival
in grade 3 follicular lymphoma, but cytological subtypes do not
predict survival. Blood. 2002 Nov 7 PMID: 12424193 PubMed
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Assessment of prognostic factors in follicular lymphoma
patients.
Int J Hematol. 2001 Apr;73(3):363-8. PMID: 11345204 PubMed
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Pregnancy in the patient with lymphoma does not predict an
adverse prognosis Year: 2002 Abstract No: 1141
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Prognosis of follicular lymphoma: a predictive model based on
a retrospective analysis of 987 cases. Intergruppo Italiano
Linfomi. Blood. 2000 Feb 1;95(3):783-9. PMID: 10648386 PubMed
|
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Prognostic significance of Ki-67 nuclear proliferative
antigen, bcl-2 protein, and p53 expression in follicular and
diffuse large B-cell lymphoma. Med Oncol. 2001;18(1):15-22. PMID:
11778965 PubMed
"Prognostic factors for overall survival in the
multivariate analysis were age (p = 0.02) and LDH (p = 0.003).
Time to progression was worse among follicular lymphoma with high
p53 expression than with mild/moderate p53 expression (p =
0.009)."
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Cutaneous b-cell lymphoma
| Prognostic Factors in Primary Cutaneous B-Cell Lymphoma: The
Italian Study Group for Cutaneous Lymphomas. J Clin Oncol. 2006
Feb 21; PMID:
16492713
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Hodgkins Lymphoma
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NEW: Better Prognosis
for Patients with Lymphocyte-predominant Hodgkin’s Lymphoma patient.cancerconsultants.com
"In order to better understand characteristics of LPHL
[Lymphocyte-predominant HL], researchers from Germany conducted an
analysis of 8,298 HL patients treated within a German medical
trial to compare patient characteristics and treatment outcomes
among cHL [classical HL) patients and others diagnosed with LPHD .
"
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| NEW: Prognostic impact of bone involvement in Hodgkin lymphoma.
Neoplasma. 2008;55(2):96-100. PMID: 18237246
... bone involvement is a relatively common finding in HL and is
not an independent adverse prognostic factor. Key words: Hodgkin lymphoma - bone involvement - prognostic factors.
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| MAL [a gene also expressed in mediastinal (thymic) large
B-cell lymphoma] is expressed in a subset of Hodgkin lymphoma and
identifies a population of patients with poor prognosis. Am J Clin
Pathol. 2006 May;125(5):776-82. PMID:
16707382 | Related
articles
"Expression correlated with nodular sclerosis subtype, and
within this subtype, with grade 2 histology."
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Marginal Zone/MALT
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Splenic marginal zone lymphoma: a prognostic model for
clinical use.
Blood. 2006 Feb 21; PMID:
16493005
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T-cell
TOPIC
SEARCH - PubMed
| Marker Expression in Peripheral T-Cell Lymphoma: A Proposed
Clinical-Pathologic Prognostic Score. J Clin Oncol. 2006 Apr 24; PMID:
16636342
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Immunophenotypic and molecular features, clinical outcomes, treatments, and prognostic factors associated with subcutaneous panniculitis-like T-cell lymphoma: a systematic analysis of 156 patients reported in the literature.
Cancer. 2004 Sep 15;101(6):1404-13. PMID: 15368328
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International
Prognostic Indexes |
Prognostic Indexes
IPI and FLIPI
"Because most of the
prognostic studies are based on a retrospective analysis of historical
data, they must be interpreted with caution at a time when treatment
modalities are changing." - herkules.oul
FLIPI
DISCUSSION
(Clinical Implications):
"The FLIPI may be used for selecting treatment in individual
patients. In patients with a good prognosis (0-1 adverse
factor), the 10-year overall survival is 71%. This
indicates that optimal treatment in these patients has to
avoid toxicity and to preserve quality of life.
Involved-field radiation therapy for patients with limited
disease and an initial "no treatment policy," for patients
with disseminated disease may be recommended outside clinical
trials. In contrast, patients with high-risk FL have a
median survival around 5 years. Innovative approaches such as
the combination of CVP (cyclophosphamide, vincristine, prednisone)
or CHOP (CVP plus doxorubicin) and anti-CD20 monoclonal
antibody,32 purine analog-based
regimens,33 and autologous stem cell
transplantation30 followed by vaccine
therapies34 may be studied in this
subgroup. All these approaches have been so far evaluated
in phase 2 studies. The size of the high-risk group (27% of
patients in the sample used for creating this index and 28%
in the sample used for validation) could allow the design
of multicenter randomized trials."
Full
Text - Blood
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International
Prognostic Index (IPI)
Designed to further clarify lymphoma
staging. The IPI [roughly] predicts the risk of disease recurrence and
overall survival:
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Age over 60 years
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Late-stage disease (Stages 3 and 4)
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More than one extranodal site
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High LDH
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Poor general health or performance |
| | | |
Source: oncologychannel.com
_____________________________________________
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| Follicular
Lymphoma International Prognostic Index (FLIPI)
Full
Text - Blood |
"FLIPI is recommended In
patients with FL at first relapse/progression, the FLIPI,
along with the presence of bulky disease and B symptoms, are
features that predict Five-year survival from progression (SFP) and
thus could be useful to select candidates for experimental
treatments." annonc.oxfordjournals.org
Five adverse prognostic factors were selected:
-
age (> 60 vs. </= 60),
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Ann Arbor stage (III-IV vs. I-II),
-
hemoglobin level (< 12
g/dL vs. >/= 12 g/dL),
-
number of nodal areas (> 4 vs. </= 4),
See graphic
-
serum LDH level (> normal vs. </= normal).
Three risk groups were defined:
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Low-risk
(0-1 adverse factor, 36 % of patients,
10-year survival of 70.7 %),
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Intermediate-risk (2 factors, 37 % of patients,
10-year survival of 51 % and a hazard-ratio of 2.3),
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Poor-risk (>/= 3 adverse factors, 27 % of patients,
10-year survival of 35.5 % and a hazard-ratio of 4.3).
See discussion in sidebar
"One point is given for each factor present at diagnosis. Patients with zero to one factors are classified as low-risk patients and have 5- and 10-year survivals of 90% and 71%, respectively.
Patients with two factors are classified as intermediate risk and they have 5- and 10-year survivals of 78% and 51%, respectively.
High-risk disease patients have three to five factors and 5- and 10-year survivals of 53% and 36%, respectively. The relative frequencies of the three risk categories are 36%, 37%, and 27%, which is a significant improvement over the IPI distribution in follicular lymphoma."
Source: Follicular Lymphoma: Management Options in the Era of Targeted Therapy
Christopher G. Peterson, MD Brad S. Kahl, MD* ~ Current Treatment Options in Oncology 2005, 6:297–308
_____________________________________________
GELF Criteria (a
guide for need of treatment of follicular NHL)
NOTE: This is a general guide. The need to begin
treatment in individual cases can vary.
One or more of
the following
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Involvement of 3 nodal sites, each with a diameter of 3 cm
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Any nodal or extranodal tumor mass with a diameter of 7 cm
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Splenomegaly
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Cytopenias (leukocytes < 1.0 x 10 /L and/or platelets < 100 x 10 /L)
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Leukemia (> 5.0 x 10 /L malignant cells)
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_____________________________________________
NCCN Guidelines: Indications to treat follicular NHL
NOTE: This is a general guide. The need to begin treatment
in individual cases can vary.
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Symptoms
(fatigue, pain, fevers...)
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Threatened
end-organ function (enlarged node obstructing bowel)
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Cytopenia
secondary to lymphoma (low blood counts)
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Bulky
disease - according to the GELF criteria: nodal or
extra-nodal
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mass (except
spleen) > 7cm in its greater diameter 2
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Steady
progression
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Patient
preference
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Elevated
serum LDH or B2-microglobulin
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involvement
of multiple nodal sites
(each with a diameter greater than 3 cm) 2
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symptomatic
splenic enlargement 2
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compressive
syndrome 2
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pleural/peritoneal
effusion 2
|
Sources:
http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf 1
PRIMA study: 2 http://prima.
gela.org/
studydoc/
1_ETUDE/PRIMA_
Protocol_
Version4.
0_Finalnonsurlig
ne.pdf
_____________________________________________
Mantle
Cell Lymphoma International Prognostic Index (MIPI)
A
new prognostic index (MIPI) for patients with advanced-stage
mantle cell lymphoma bloodjournal.hematologylibrary.org
Using data of 455 advanced stage MCL patients
treated within 3 clinical trials, we examined the
prognostic relevance of IPI and FLIPI and derived a
new prognostic index (MCL international prognostic index, MIPI)
of overall survival (OS).
According
to the MIPI, patients were classified into
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low
risk (44% of patients, median OS not
reached), |
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intermediate
risk (35%, 51 months), and |
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high
risk groups (21%, 29 months), |
based
on the 4 independent prognostic factors:
|
age, |
|
performance
status, |
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lactate
dehydrogenase (LDH), and |
|
leukocyte
count. |
|
Cell
proliferation (Ki-67) was exploratively analyzed as
an
important biologic marker and showed strong
additional
prognostic relevance. |
The
MIPI is the first prognostic index particularly suited for
MCL patients and may serve as an important tool to
facilitate risk-adapted treatment decisions in
patients with advanced stage MCL.
|
|
Specific Biomarkers |
Biomarkers
Under construction
"Indirect" indicates that
increased levels can have other causes besides lymphoma.
|
TOPIC
SEARCH microenvironment AND prognosis WEB
| PubMed
| absolute
lymphocyte count at diagnosis
Absolute lymphocyte count predicts overall survival in follicular
lymphomas.
Br J
Haematol. 2006 Sep;134(6):596-601. Epub 2006 Aug 1.
PMID:
16889618 |
|
Urinary
albumin excretion [post treatment] is a predictor of response to
treatment and disease progression in low-grade non-Hodgkin's
lymphoma. Leuk Lymphoma. 2004 Mar;45(3):547-51. (Lower is
better.) PMID:
15160917 | Related
articles |
|
Beta2-microglobulin is a
protein found on the surface of many cells, including white blood
cells. (indirect) |
|
Serum
CA125: A Tumor Marker for Monitoring Response to Treatment and
Follow-up in Patients with Non-Hodgkin’s Lymphoma theoncologist.alphamedpress.org |
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Strong
Expression of FOXP1 Identifies a Distinct Subset of Diffuse Large
B-Cell Lymphoma Patients with Poor Outcome. Blood. 2004 Jul 6 PMID:
15238418 |
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Lactate Dehydrogenase (LDH) is an enzyme that
is expressed at higher levels when lymphocytes are dividing.
(indirect) |
| Ki-67
- proliferation index (indirect)
|
"Typically,
reactive follicles are characterized by absence of bcl-2
expression and a high Ki-67-defined cell proliferation index,
in contrast to the typical low grade follicular lymphoma, in
which the cells are bcl-2-positive and show a very low
Ki67-defined cell proliferation index." phenopath.com |
|
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Diffuse
component |
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BCL-2 -
PAL |
| BCL-2
Negative |
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BCL-6
|
"Rearrangement of the bcl-6 gene
correlated with a favorable clinical outcome in Diffuse
Large Cell Lymphoma" |
|
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BLyS:
Expression of BLyS and Its Receptors in B-Cell Non-Hodgkin
Lymphoma: Correlation With Disease Activity and Patient Outcome.
Blood. 2004 Jul 13 PMID:
15251985 |
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Prediction
of survival in follicular lymphoma based on molecular features of
tumor-infiltrating immune cells. N Engl J Med. 2004 Nov
18;351(21):2159-69.
PMID:
15548776 |
|
Serologic
detection of diffuse large B-cell lymphoma-associated antigens.
Int J Cancer. 2004 Jul 1;110(4):563-9. PMID:
15122589 | abstracts |
| Immunohistochemical detection of ZAP-70
in 341 cases of non-Hodgkin and Hodgkin lymphoma; May 2004 nature.com
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