Search: - PubMed Abstracts:
are some abstracts on Follicular Grade 3, highlighting the
controversy. Abstracts are listed in chronological order, the
top being most recent.
NCCN GUIDELINES for grade 3: "Follicular lymphoma, grade 3
is an area of controversy. The distinction between follicular
grade 3a and 3b has not been shown to have clinical significance to
Follicular lymphoma grade 3 is commonly treated according to NCCN
guidelines for DLBCL (BCEL-1). Any area of diffuse large
B-cell lymphoma (DLBCL) in a follicular lymphoma of any grade should
be diagnosed and treated as a DLBCL." - April 2011
Follicular non-Hodgkin lymphoma grades 3A and 3B have a
similar outcome and appear incurable with anthracycline-based
1. J. Shustik1,*, 2. M. Quinn1, 3. J. M. Connors1, 4.
R. D. Gascoyne2, 5. B. Skinnider2 and 6. L. H. Sehn1
April 27, 2010.
Background: The revised World Health Organization (WHO)
classification maintains a histological grading system (grades 1–3)
for follicular lymphoma (FL) and subdivides grade 3 into 3A (FL3A)
and 3B (FL3B) subtypes. Optimal therapy of FL grade 3 and its
potential curability with anthracycline-based chemotherapy remain
Patients and methods: We carried out a retrospective
population-based analysis evaluating the clinical characteristics
and outcome of FL3A and FL3B as strictly defined by WHO diagnostic
Using the BC Cancer Agency Lymphoid Cancer Database, 161 patients
with FL grade 3 were identified and, following detailed pathology
review, composed of 139 with FL3A and 22 with FL3B.
Results: Patients with FL3B had a higher overall International
Prognostic Index (IPI) score than FL3A patients (P = 0.03), though
no significant difference in individual IPI risk factor frequencies
More patients with FL3B received front-line
anthracycline-containing chemotherapy (82% versus 36%, P ≤ 0.001).
With median follow-up of 45 months, no difference in
disease-specific survival (P = 0.74) or overall survival (OS) (P =
0.87) was found between FL3A and FL3B and no survival curve plateau
Analysis limited to FL3A patients showed no OS advantage with
front-line anthracycline use (P = 0.33).
Conclusion: Using strict diagnostic criteria, there appears to be no
difference in outcome between patients with FL3A and FL3B and no
evidence of curability with anthracycline-based therapy.
Oncol. 2008 Mar;19(3):553-9.
The addition of rituximab to CHOP chemotherapy improves overall
and failure-free survival for follicular grade 3 lymphoma.
Overman MJ, Feng L, Pro B, McLaughlin P, Hess M, Samaniego F, Younes
A, Romaguera JE, Hagemeister FB, Kwak L, Cabanillas F, Rodriguez MA,
Source: Department of Gastrointestinal Medical Oncology, University
of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard,
Houston, TX 77030, USA.
BACKGROUND: The benefit of adding rituximab to anthracycline-based
therapy for follicular lymphoma grade 3 has not been studied.
PATIENTS AND METHODS: We retrospectively reviewed the records of
45 patients with follicular grade 3 lymphoma who were treated with
rituximab and the combination of cyclophosphamide, doxorubicin,
vincristine, and prednisone (CHOP) at The University of Texas MD
Anderson Cancer Center. Response rate, failure-free survival (FFS),
and overall survival (OS) were estimated and a historical comparison
to CHOP-only-treated patients was made.
RESULTS: The International Prognostic Index (IPI) distribution was
47% low, 36% low intermediate, 13% high intermediate, and 4% high
The complete response rate was 96%. Forty-four of 45 patients are
still alive. Median follow-up for the alive patients is 3.5 years.
The 3-year FFS rate according to the IPI was 80% [95% confidence
interval (CI) 64% to 100%] in low, 81% in low intermediate (95% CI
64% to 100%), and 50% (95% CI 25% to 100%) in
high-intermediate/high-risk patient group.
The addition of rituximab to CHOP improved both 5-year FFS, 71%
(95% CI 58% to 87%) compared with 44% (95% CI 36% to 55%) with P
value of 0.019, and 5-year OS, 98% (95% CI 93% to 100%) compared
with 75% (95% CI 67% to 84%) with P value of 0.0034.
CONCLUSION: The addition of rituximab to CHOP provided a high
response rate and excellent early survival. Poor-risk patients
continue to demonstrate a high rate of failure despite the use of
1: Ann Oncol. 2006 Jun;17(6):920-7. Epub 2006 Mar 8. Links
Patients with grade 3 follicular lymphoma have prolonged relapse-free survival following anthracycline-based chemotherapy: the Nebraska Lymphoma Study Group
Ganti AK, Weisenburger DD, Smith LM, Hans CP, Bociek RG, Bierman PJ, Vose JM, Armitage JO.
Department of Internal Medicine, Division of Oncology/Hematology, University of Nebraska Medical Center, Omaha, USA.
BACKGROUND: The aim of the study was to determine the outcome and clinical features predictive of survival in patients with follicular lymphoma (FL) treated aggressively and to determine the rate of disease-specific mortality in patients with grade 3 FL (FL3).
MATERIALS AND METHODS: Four hundred and twenty-one patients with FL who were treated with various anthracycline-based chemotherapy regimens were included in this retrospective study.
RESULTS: Patients with FL3 and a diffuse component of >50% had the worst outcome, with a hazard ratio of dying of 2.2 (95% CI 1.4-3.4) compared with patients with FL1 or FL2, and a ratio of 1.6 (95% CI 1.02-2.5) compared with FL3 with a diffuse component of < or =50% by multivariate analysis (P = 0.0026).
Patients with FL3a had an outcome similar to those with FL3b. In patients with FL3 and a diffuse component of < or =50%, the overall and event-free survival curves showed a plateau for patients younger than 60 years of age. However, there were no differences in the cumulative incidence of relapse/progression or lymphoma-specific/treatment-related mortality between the two age groups.
CONCLUSIONS: Less than half of the patients with FL3 and a diffuse component of < or =50% treated with anthracycline-based combination chemotherapy will relapse and relapses are uncommon after 6 years. Older patients should be offered the same aggressive chemotherapy as younger patients.
Letter to the editor from Blood regarding
the use of the FLIPI in GRADE # follicular
Blood, 15 June 2005, Vol. 105, No. 12, pp. 4892-4893
CORRESPONDENCE To the editor:
Does the FLIPI apply to grade 3 follicular lymphoma?
the publication of a score (Follicular Lymphoma International
Prognostic Index [FLIPI]) assisting in the choice of treatment for
patients with newly diagnosed follicular lymphoma (FL).1
As the authors state, treatment options for this disease
range from "watch and wait" to allogeneic bone marrow
transplantation, and the selection of the best available option will
be favored by a realistic estimation of the expected survival for
each particular patient.
The 5 independent prognostic factors retained in the FLIPI reflect
important characteristics of the patient (age), of the disease
extension and clinical aggressiveness (stage and number of nodal
sites involved, lactose dehydrogenase [LDH]), and of the tumor-host
interaction (hemoglobin level).
Surprisingly enough, histology grade, a disease
characteristic considered by many clinicians to be of paramount
importance for prognosis and choice of treatment, is missing from
the index and was not even significant in the univarate
The absence of this parameter from the index and the omission of any
discussion about this fact in the paper could suggest that
histologic grade is indeed not relevant to patient survival and
should therefore not be taken as an important information.
We believe that this misunderstanding results from
a bias that is not sufficiently covered in the article and that
should be clarified.
It was long recognized that an important proportion of large cells
(centroblasts) at histologic examination (an observation referred to
as grade 3 in the current World Health Organization [WHO]
classification) does confer to FL a worse prognosis, despite
apparently favorable clinical prognostic features.2,3 Nevertheless,
the outcome of these cases can be similar to the forms with less
centroblasts when they are treated with an anthracycline-containing
regimen [ie, CHOP].4,5
This information was known in 19856 (the year of the start
of data collection for the FLIPI) and, although details on treatment
are not given in the paper, it is probable that the majority of
grade 3 FLs of this data set were treated with anthracyclines, thus
influencing the prognosis.
Even though the article states that "none of the
treatments given during the period of inclusion has significantly
changed the natural history of the disease,"1(p1264) this only
applies to cases with histologic grades 1 and 2, while for WHO grade
3 we have reason to
think that treatment did indeed influence survival, and therefore
interacted with other prognostic factors.
The FLIPI could have been a more reliable index if grade 3 FLs
were not included in the analysis. We believe that for grades 1 and
2 FL, treatment should be selected based on a number of factors,
including the FLIPI score, but an anthracycline-containing regimen
should still be favored for patients with grade 3 FL, independent of
their FLIPI index.
See response below.
Michele Ghielmini, and Oreste Mora
Correspondence: Michele Ghielmini and Oreste Mora, Oncology
of Southern Switzerland, Ospedale San Giovanni, 6500 Bellinzona,
Switzerland; e-mail: email@example.com
1. Solal-Céligny P, Roy P, Colombat P, White, et al. Follicular
Lymphoma International Prognostic Index. Blood. 2004;104:
1258-1265.[Abstract/Free Full Text]
2. Martin AR, Weisenburger DD, Chan WC, et al. Prognostic value of
cellular proliferation and histologic grade in follicular lymphoma.
Blood. 1995;85: 3671-3678.[Abstract/Free Full Text]
3. Rodriguez J, McLaughlin P, Hagemeister FB, et al. Follicular
cell lymphoma: an aggressive lymphoma that often presents with
favorable prognostic features. Blood. 1999;93:
2202-2207.[Abstract/Free Full Text]
4. Nathwani BN, Harris NL, Weisenburger D. Follicular lymphoma. In:
Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health
Organization Classification of Tumours. Tumours of haematopoietic
lymphoid tissues. Albany, NY: WHO Publication Center; 2001: 162-167.
5. Bartlett NL, Rizeq M, Dorfman RF, Halpern J, Horning SJ.
large-cell lymphoma: intermediate or low grade? J Clin Oncol.
1349-1357.[Abstract/Free Full Text]
6. Glick JH, McFadden E, Costello W, Ezdinli E, Berard CW, Bennett
Nodular histiocytic lymphoma: factors influencing prognosis and
implications for aggressive chemotherapy. Cancer. 1982;49:
840-845.[Medline] [Order article via Infotrieve]
FLIPI in grade 3 follicular lymphoma We agree with Prof Ghielmini
that grade 3 follicular lymphoma is in many cases a more aggressive
disease than other follicular lymphomas, although this is an area of
Grade 3b follicular lymphoma especially shares the
prognosis of and requires treatment approaches similar to that of
diffuse large B-cell lymphoma.2 We welcome the opportunity to
comment further on the Follicular Lymphoma International Prognostic
Index (FLIPI) observations about grade 3 follicular lymphoma.
First, a central pathology review was not realistic for
the 5000 FLIPI cases. Since there are known inter-observer
variations in the assignment of histologic grade,3,4 we felt we
would introduce a bias if we excluded these cases arbitrarily.
Moreover, they represented only 9% of the entire FLIPI population.
Second, the IPI appears to have one of the same shortcomings for
grade 3 follicular lymphoma as it does for all follicular lymphomas,
namely the identification of only a small (15%-20%) fraction of
cases with high risk.5,6 Thus the inclusion of grade 3 cases in the
FLIPI, and the applicability of the FLIPI to grade 3 follicular
lymphoma, represents a potential benefit to patient management.
But we completely agree with Prof Ghielmini's observation that an
anthracycline-containing regimen is favored for patients with grade
3 follicular lymphoma.
It was beyond the scope of the initial FLIPI project to
analyze in any detail the various treatment modalities used.
Moreover, such a retrospective analysis would be open to valid
criticism. But we agree that the literature supporting the inclusion
of anthracyclines in grade 3 follicular lymphoma5,6 is less
controversial than the comparable literature in other follicular
We thank him for drawing attention to this important
topic. The F2 study (coordinated by M. Federico) is ongoing to
determine the influence of grade and the impact of diffuse areas on
~ Peter McLaughlin, Philippe Solal-Céligny, on behalf of
the Scientific Committee of the FLIPI
Correspondence: Philippe Solal-Céligny, Centre J. Bernard, 9 rue
Beauverger, 72000 Le Maur, France; e-mail: firstname.lastname@example.org
1. Armitage JO, Cavalli F, Zucca E, Longo DL. Follicular lymphoma.
Text Atlas of Lymphomas. Martin Dunitz Ltd; 1999: 13-21.
2. Bosga-Bouwer AG, van Imhoff GW, Boonstra R, et al. Follicular
lymphoma grade 3b includes 3 cytogenetically defined subgroups with
primary t(14;18) 3q27 or other translocations: t(14;18) and 3q27 are
mutually exclusive. Blood. 2003;101: 1145-1154.[CrossRef]
3. Horning SJ. Something old, something new, something subjective,
something déjà vu. J Clin Oncol. 2003;21: 1-2.[Free Full Text]
4. Hans CP, Weisenburger DD, Vose JM, et al. A significant diffuse
component predicts for inferior survival in grade 3 follicular
lymphoma, but cytologic types do not predict survival. Blood.
2003;101: 2363-2367.[Abstract/Free Full Text]
5. Wendum D, Sebban C, Gaulard P, et al. Follicular large-cell
lymphoma treated with intensive chemotherapy: an analysis of 89
included in the LNH87 trial and comparison with the outcome of
large B-cell lymphoma. J Clin Oncol. 1997;15:
6. Rodriguez J, Mc Laughlin P, Hagemeister FB, et al. Follicular
cell lymphoma: an aggressive lymphoma that often presents with
favorable prognostic features. Blood. 1999;93: 2002-2007.
7. Rigacci L, Federico M, Martinelli M, et al. The role of
anthracyclines in combination chemotherapy for the treatment of
follicular lymphomas. Leuk Lymphoma. 2003;44:
1911-1917.[CrossRef][Medline] [Order article via Infotrieve]
Related Article in Blood Online:
Follicular Lymphoma International Prognostic Index
Philippe Solal-Céligny, Pascal Roy, Philippe Colombat, Josephine
White, Jim O. Armitage, Reyes Arranz-Saez, Wing Y. Au, Monica Bellei,
Pauline Brice, Dolores Caballero, Bertrand Coiffier, Eulogio
Conde-Garcia, Chantal Doyen, Massimo Federico, Richard I. Fisher,
Javier F. Garcia-Conde, Cesare Guglielmi, Anton Hagenbeek, Corinne
Haïoun, Michael LeBlanc, Andrew T. Lister, Armando Lopez-Guillermo,
Peter McLaughlin, Noël Milpied, Pierre Morel, Nicolas Mounier,
J. Proctor, Ama Rohatiner, Paul Smith, Pierre Soubeyran, Hervé
Umberto Vitolo, Pier-Luigi Zinzani, Emanuele Zucca, and Emili
Blood 2004 104: 1258-1265. [Abstract] [Full Text]
Biol Blood Marrow Transplant. 2006 Jun;12(6):641-7.
Related Articles, Links
Does follicularity in large cell lymphoma predict
outcome after autologous stem cell transplantation?
Krishnan A, Nademanee A, Fung H, Angelopoulou M, Molina A, Gaal
K, Dagis A, Palmer J, Alvarnas J, Slovak M, Kogut N, Popplewell L,
Rodriguez R, Schriber J, Wang S, Forman SJ.
Division of Hematology/Hematopoietic Cell Transplantation, City of
Hope Comprehensive Cancer Center, Duarte, California 91010, USA. email@example.com
The purpose of this study was to evaluate whether
follicular histology in large cell lymphoma influences treatment
outcomes after autologous stem cell transplantation (ASCT).
It remains an area of controversy whether the
natural history of follicular large cell lymphoma (FLCL) is akin to
diffuse large cell lymphoma (DLCL) with curative potential or is more
similar to indolent follicular lymphomas with a pattern of late
relapses after intensive chemotherapy.
Although ASCT is a potentially curative treatment
for patients with recurrent DLCL, the effectiveness of this approach
in patients with FLCL is unclear.
We undertook a retrospective analysis of 332
patients with large cell lymphoma who underwent ASCT at the City of
Hope Comprehensive Cancer Center. With a median follow-up of 31
months, the projected 10-year overall survival and disease-free
survival were similar between patients with FLCL and DLCL. Analysis of
prognostic factors demonstrated that although age, chemotherapy
refractoriness, and disease status at the time of ASCT were predictive
of overall survival/disease-free survival, follicularity did not
influence the outcome.
Furthermore, the similar plateau in the survival
curve for the DLCL and FLCL patients suggests that the behavior of
FLCL is similar to that of DLCL and that FLCL is potentially curable
7 July 2003, Volume 89, Number 1, Pages 36-42
Outcome of follicular lymphoma grade 3: is anthracycline necessary as
Chau1, R Jones1, D Cunningham1, A Wotherspoon2, N
Maisey1, A R
Norman3, P Jain4, L Bishop1, A Horwich5 and D Catovsky4
Presented at the Eighth International Conference on Malignant
Lymphoma, Switzerland, June 2002.
A grading system (grades 1-3) for follicular
lymphoma (FL) is used in the WHO classification for lymphoid
malignancies based on the absolute number of centroblasts in the
neoplastic follicles. Grade 3 FL is further subdivided into 3a and 3b
depending on the presence or absence of centrocytes.
A total of 231 patients with FL, referred from 1970 to 2001, were
identified from our prospectively maintained database. Original
diagnostic materials were available for review on 215 patients and
these were reclassified according to the WHO grading system.
Follicular lymphoma grades 1, 2 and 3 accounted for 92, 68 and 55
No significant overall survival (OS) differences were observed among
FL grades 1-3 (log rank P=0.25) or between grades 3a and 3b (log rank
P=0.20). No significant failure-free survival (FFS) differences were
observed among FL grades 1-3 (log rank P=0.72) or between grades 3a
and 3b (log rank P=0.11).
First-line anthracyclines did not influence OS or FFS (log rank
P=0.86, P=0.58, respectively) in patients with FL grade 3. There are
long-term survivors among patients with FL grade 3 with a continuing
risk of relapse. Anthracyclines did not appear to influence survival
or disease relapses when given as front-line therapy in our series.
The role of anthracyclines should be further evaluated in large randomized
British Journal of Cancer (2003) 89, 36-42. doi:10.1038/sj.bjc.6601006
1: Ann Oncol 2000 Dec;11(12):1551-6
Follicular large cell lymphoma: long-term follow-up of 62 patients
treated between 1973-1981.
Rodriguez J, McLaughlin P, Fayad L, Santiago M, Hess M, Rodriguez MA,
Romaguera J, Hagemeister F, Kantarjian H, Cabanillas F.
University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
PURPOSE: Investigators disagree on whether follicular large cell
lymphoma (FLCL) behaves like other follicular lymphomas, with no
plateau in the survival curve, or as a more aggressive but potentially
curable lymphoma. We reported in 1984 results for 62 FLCL patients
treated at our institution; the current report updates those
PATIENTS AND METHODS: Sixty-two patients referred
from 1973-1981, including fifteen (24%) patients with Ann Arbor stage
I-II and forty-seven (76%) with stage III-IV FLCL.
Seven patients received radiation (XRT) alone, forty
patients XRT and chemotherapy, and fifteen patients received
RESULTS: The median follow-up was 14.7 years.
The median survival was 5.1 years, with 21% alive at
The failure-free survival (FFS) at 10 years was 31%.
Univariate analysis revealed that age, Ann Arbor stage, and the
International Index correlated with survival. Performance status,
number of platelets, and LDH correlated with failure-free survival.
CONCLUSIONS: FLCL responds to doxorubicin-based
regimens similarly to diffuse large cell lymphoma. Patients with FLCL
have the potential for prolonged failure-free survival. Variables that
predict the survival in aggressive lymphomas apply as well in this
type of lymphoma.
Effect of follicularity on autologous
transplantation for large-cell non-Hodgkin's lymphoma.
J Clin Oncol 1998 Mar;16(3):844-9 (ISSN: 0732-183X) Vose JM; Bierman PJ; Lynch JC; Weisenburger DD; Kessinger A; Chan WC;
Greiner TC; Armitage JO
Department of Internal Medicine, University of
Nebraska Medical Center, Omaha 69198-3332, USA. jmvose@m...
PURPOSE: This study evaluated the outcomes of
patients who received high-dose chemotherapy (HDC) and autologous
hematopoietic stem-cell transplantation (ASCT) for large-cell
non-Hodgkin's lymphoma (NHL) and the effect of a follicular versus a
PATIENTS AND METHODS: The prognostic factors in 289
patients who underwent HDC and ASCT for large-cell NHL between May
1983 and December 1996 were analyzed.
RESULTS: With a median follow-up duration of 24
months for surviving patients (range, 3 to 131 months),
112 of 289 (39%) were alive and 82 of 289 (28%) were
In a multivariate analysis, the factors associated
with a poorer failure-free survival (FFS) included a lactic
dehydrogenase (LDH) level greater than normal (P < .0001), three or
more prior chemotherapy regimens received (P < .01), a mass > or
= 10 cm at transplant (P < .01), and diffuse histology at the time
of transplant (P = .026).
Patients who received HDC and ASCT for large-cell
NHL in the good-prognosis category (normal LDH, < three prior
chemotherapy regimens, no large mass, and not chemotherapy-resistant)
had a 5-year survival rate of 45%. Within the good-prognosis group,
patients with diffuse large-cell NHL had a 5-year survival rate of 42%
compared with 58% for patients with follicular large-cell (FLC)
lymphoma (P = .05).
CONCLUSION: Good-prognosis patients with FLC
histology who receive HDC and ASCT have an improved survival compared
with good-prognosis patients with a diffuse large-cell histology.
2: Blood 1999 Apr 1;93(7):2202-7 Related Articles,
Follicular large cell lymphoma: an aggressive lymphoma that often
presents with favorable prognostic features.
Rodriguez J, McLaughlin P, Hagemeister FB, Fayad L, Rodriguez MA,
Santiago M, Hess M, Romaguera J, Cabanillas F.
University of Texas M.D. Anderson Cancer Center, Houston, TX 77030,
It is debated whether follicular large cell lymphoma (FLCL) has a
clinical behavior that is distinct from indolent follicular lymphomas,
and whether there is a subset of patients who can be potentially
We report here our experience with 100 FLCL patients
treated at our institution since 1984 with three successive programs.
We evaluated the predictive value of pretreatment clinical features,
including two risk models, the Tumor Score System and the
International Prognostic Index (IPI).
With a median follow-up of 67 months, the 5-year
survival is 72% and the failure-free survival (FFS) is 67%, with a
possible plateau in the FFS curve, particularly for patients with
stage I-III disease.
Features associated with shorter survival included
age >/=60, elevated lactic dehydrogenase (LDH) or
beta-2-microglobulin (beta2M), advanced stage, and bone marrow
Stage III patients had significantly better survival
than stage IV patients (P <.05). By the IPI and Tumor Score System,
80% of the patients were in the lower risk groups; both systems
stratified patients into prognostic groups.
Patients with FLCL have clinical features and
response to treatment similar to that reported for diffuse large cell
Prognostic risk systems for aggressive lymphomas are
useful for FLCL. A meaningful fraction of patients may possibly be
cured when treated as aggressive lymphomas.
Full text: http://www.bloodjournal.org/cgi/content/full/93/7/2202
3: J Clin Oncol 1997 Apr;15(4):1654-63
Follicular large-cell lymphoma treated with
intensive chemotherapy: an analysis of 89 cases included in the LNH87
trial and comparison with the outcome of diffuse large B-cell
Groupe d'Etude des
Lymphomes de l'Adulte.
Wendum D, Sebban C, Gaulard P, Coiffier B, Tilly H, Cazals D, Boehn A,
Casasnovas RO, Bouabdallah R, Jaubert J, Ferrant A, Diebold J, de
Mascarel A, Gisselbrecht C.
Services d'Anatomie et Cytologie Pathologiques, Hopital Saint-Antoine,
PURPOSE: The aims of this study were as follows: (1) to analyze
clinical, histopathologic characteristics, treatment outcome, and
prognostic factors of patients with follicular large-cell lymphoma (FLCL);
and (2) to compare them with those of patients with diffuse large
B-cell lymphoma (DLCL) treated in the same therapeutic trial.
PATIENTS AND METHODS: Eighty-nine FLCL patients who
were histologically reviewed and who received an intensive
chemotherapy regimen according to the LNH 87 protocol were analyzed
and compared with 1,096 B-cell DLCL patients included in the same
After intensive induction treatment, 59 patients
(67%) achieved a complete remission [CR].
Estimated 5-year survival was 59%, and estimated
5-year freedom from progression (FFP) was 39%.
Prognostic factors associated with shorter FFP
age greater than 60 years (P = .02),
advanced clinical stage (P = .01),
abnormal lactic dehydrogenase (LDH) level (P = .02),
abnormal beta-2 microglobulin (P = .02),
B symptoms (P = .03),
bone marrow involvement (P = .04),
and high expression of bcl-2 protein (P = .05).
When compared with B-cell DLCL patients, FLCL
patients were younger (P = .02), had a better Eastern Cooperative
Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04),
more advanced clinical stages (P < .001), and more bone marrow
involvement (P = .02).
No significant difference was observed between FLCL
and DLCL patients for response to therapy (67% v 67% of CR), 5-year
overall survival (58% v 51%), 5-year disease-free survival (53% v
57%), or FFP survival (39% v 43%).
FLCL patients have a favorable response rate and
survival when treated with intensive chemotherapy. Their outcome is
similar to that of B-cell DLCL patients, and a long-term FFP is
observed for a substantial number of patients.
Some adverse prognostic factors (including those of
the International Prognostic Index, bone marrow involvement, and
beta-2 microglobulin) have been identified to define a subset of
patients who require other therapeutic approach.
PMID: 9193366 [PubMed - indexed for MEDLINE]
4: J Clin Oncol 1994 Jul;12(7):1349-57
Follicular large-cell lymphoma: intermediate or low grade?
Bartlett NL, Rizeq M, Dorfman RF, Halpern J, Horning SJ.
Department of Medicine, Stanford University School of Medicine, CA.
PURPOSE: To evaluate the benefit of anthracycline-based chemotherapy,
identify prognostic factors, and determine the value of the
International Prognostic Factors Index for patients with follicular
large-cell (FLC) lymphoma.
PATIENTS AND METHODS: This retrospective study
includes 96 patients with FLC lymphoma treated at Stanford University
Medical Center between 1969 and 1991.
Fifty-five patients received doxorubicin plus
cyclophosphamide-containing chemotherapy regimens,
21 patients received other chemotherapy
15 patients received radiotherapy only,
and five patients received no initial therapy.
Thirty-four patients had stage I or II disease and
62 patients had stage III or IV disease.
With a median follow-up duration of 5.2 years
(range, 1 to 18), the actuarial 5- and 10-year
overall survival rates were 75% and 54%, with actuarial 5- and 10-year
freedom from progression (FFP) rates of 53% and 42%,
Patients treated with chemotherapy regimens that
contained both doxorubicin and cyclophosphamide had a superior
actuarial 10-year FFP rate (55% v 25%, P = .06) and overall survival
rate (65% v 42%, P = .04) compared with patients treated with other
Only one patient treated with doxorubicin plus
cyclophosphamide relapsed after 3 years. In the multivariate analysis,
discordant lymphoma and treatment with chemotherapy regimens not
containing both cyclophosphamide and doxorubicin predicted for worse
FFP and overall survival rates.
In addition, poor performance status and increasing
areas of diffuse histology predicted for a worse survival, while
anemia and male sex predicted for a worse FFP. The age-specific
International Index was useful in predicting outcome; however, few
patients with FLC lymphoma had high-risk features.
The plateau in FFP implies that patients with FLC
lymphoma enjoy sustained remissions after standard anthracycline-based
chemotherapy. FLC lymphoma should continue to be approached as an
intermediate-grade lymphoma with curative intent.
5: J Clin Oncol 1993 Feb;11(2):218-24
Clinical features and prognosis of follicular large-cell lymphoma: a
report from the Nebraska Lymphoma Study Group.
Anderson JR, Vose JM, Bierman PJ, Weisenberger DD, Sanger WG, Pierson
J, Bast M, Armitage JO.
Department of Preventive and Societal Medicine, University of Nebraska
Medical Center, Omaha 69198-4350.
PURPOSE: Our purpose was to describe the treatment outcome of patients
with follicular large-cell lymphoma (FLCL) and to identify prognostic
factors that affect the treatment outcome.
PATIENTS AND METHODS: Between 1980 and 1991, 107
newly diagnosed, previously untreated
patients with FLCL were prospectively treated using treatment plans of
the Nebraska Lymphoma Study Group (NLSG).
Most stage I/II patients received two to three
cycles of one of four closely related six-drug combination
chemotherapy regimens (cyclophosphamide, doxorubicin or mitoxantrone,
and procarbazine, plus bleomycin, vincristine, and prednisone or
dexamethasone [CAP/BOP I-IV]) plus involved-field radiotherapy; 10
patients received involved-field irradiation only.
Stage III/IV patients received six to eight cycles
RESULTS: Forty-four percent of patients had stage
I/II disease. Stage I/II patients were older and more often female
than stage III/IV patients. Cytogenetic studies were available on 35
patients: seven were normal; the most common abnormality was a
translocation involving 14q32. Abnormalities of 1p or 1q were also
common, often secondary to a 14q32 abnormality. The median follow-up
of surviving patients is 2 years.
The complete response rates observed were stage
I/II, 88%; stage III/IV, 49%.
Complete response rates were affected by both age
and tumor bulk. Failure-free survival (FFS; time to first occurrence
of progression, relapse after response, or death from any cause) at 3
years was estimated to be 61% for stage I/II patients and 34% for
stage III/IV patients.
Survival at 3 years was estimated to be 76% and 61%,
FFS of stage III/IV patients was poorer for stage IV
patients and those with composite lymphomas. Significantly poorer
survival was only seen in patients older than 70 years of age.
CONCLUSION: A proportion of stage I/II FLCL patients
may obtain long-term disease control with combination chemotherapy
plus radiotherapy. Results for patients with stage III/IV FLCL are
similar to those seen for other follicular lymphomas.
These are two articles on the pathology of Grade 3
Re: Grade 3 FLCL--abstracts for Linda R.
Cytomorphologic, immunohistochemical, and cytogenetic profiles of
follicular lymphoma: 2 types of follicular lymphoma grade 3.
Blood 2002 May 15;99(10):3806-12 (ISSN: 0006-4971)
Ott G; Katzenberger T; Lohr A; Kindelberger S; Rudiger T; Wilhelm M;
Kalla J; Rosenwald A; Muller JG; Ott MM; Muller-Hermelink HK
Pathologisches Institut and Poliklinik fur Innere Medizin, University
of Wurzburg, Germany. path042@m...
Follicular lymphoma (FL) grades 1 and 2 are regarded
as a distinct disease entity, whereas data suggest that FL grade 3
might be an inhomogeneous tumor category.
To define the biologic spectrum of FL, 89
follicular lymphomas were studied for their cytologic composition,
antigen expression, mitotic and proliferation indices, cytogenetics,
and clinical data. In contrast to the homogeneous appearance of
FL grades 1 and 2 (29 and 33 cases, respectively), 2 types of FL
grade 3 were recognized.
Eleven cases of FL 3a displayed structural features
similar to those of FL 1 and 2 and were composed of centroblasts and
centrocytes, whereas 16 cases of FL 3b, with (n = 4) or without (n =
12) a diffuse large B-cell lymphoma component (DLBL) (FL 3b +/- DLBL),
consisted exclusively of blasts.
In contrast to FL 3a, FL 3b +/- DLBL were CD10(+) in
only 50% of cases and displayed plasmacytoid differentiation in 44% of
cases. Although FL3a was t(14; 18)+ in 8 of 11 (73%) cases, only 2 of
16 (13%) FL3b +/- DLBLs harbored this translocation.
In contrast, chromosomal breaks at 3q27 were
encountered in 7 of 16 (44%) FL 3b +/- DLBL in contrast to only 2 of
11 (18%) FL 3a, and the spectrum of secondary aberrations in FL 3b +/-
DLBL was similar to that of diffuse large B-cell lymphoma.
We conclude, therefore, that FL grade 3 is a
heterogeneous disease group and that the distinction proposed in the
new World Health Organization classification between FL 3a (with
centrocytes) and FL3b (without centrocytes) is of biologic, and
possibly clinical, importance.
Decreased CD10 expression in grade III and in
interfollicular infiltrates of follicular lymphomas.
Am J Clin Pathol 2001 Jun;115(6):862-7 (ISSN:
0002-9173) Eshoa C; Perkins S; Kampalath B; Shidham V; Juckett M;
Chang CC Dept of Pathology, Medical College of Wisconsin, 9200 W
Milwaukee, WI 53226, USA.
CD10 expression in various grades and
interfollicular infiltrates of follicular lymphoma (FL) has not been
well documented. Immunohistochemical staining for CD10 (clone 56C6)
was performed on paraffin-embedded tissue from 26 cases of classic
Negative or weak expression of CD10 was more
frequent in grade III (5/6 [83%]) than in grade I FLs (3/15 [20%]).
CD10+ interfollicular infiltrates were present in 16 cases. Six (38%)
of 16 cases showed that CD10 expression was strong or moderate in
follicular areas but weak or negative in interfollicular infiltrates.
Our results suggest that CD10 expression is frequently weak to
negative in grade III and in interfollicular infiltrates of FLs.
Therefore, lack of CD10 expression on small
specimens, such as from needle core biopsy or fine-needle aspiration,
does not preclude the possibility of a diagnosis of FL. Furthermore,
lack of CD10 expression in diffuse large B-cell lymphoma does not
exclude the possibility that the neoplastic lymphocytes are of
follicle center cell origin.