Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 4930-4935 ◽  
Author(s):  
Heidi Nyman ◽  
Magdalena Adde ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Minna Taskinen ◽  
Mattias Berglund ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Control Group ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractGerminal center (GC) and non-GC phenotypes are predictors of outcome in diffuse large B-cell lymphoma (DLBCL) and can be used to stratify chemotherapy-treated patients into low- and high-risk groups. To determine how combination of rituximab with chemotherapy influences GC-associated clinical outcome, GC and non-GC phenotypes were identified immunohistochemically from samples of 90 de novo DLBCL patients treated with rituximab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)–like regimen (immunochemotherapy). One hundred and four patients previously treated with chemotherapy served as a control group. Consistent with previous studies, chemotherapy-treated patients with immunohistochemically defined GC phenotype displayed a significantly better overall (OS) and failure-free survival (FFS) than the non-GC group (OS, 70% vs 47%, P = .012; FFS, 59% vs 30%, P = .001). In contrast, immunohistochemically defined GC phenotype did not predict outcome in immunochemotherapy-treated patients (OS, 77% vs 76%, P = ns; FFS, 68% vs 63%, P = ns). In comparison, International Prognostic Index (IPI) could separate the high-risk patients from low- and intermediate-risk groups (OS, 84% vs 63%, P = .030; FFS, 79% vs 52%, P = .028). We conclude that rituximab in combination with chemotherapy seems to eliminate the prognostic value of immunohistochemically defined GC- and non-GC phenotypes in DLBCL.

Prognosis of mature T cell lymphoma is poorer than that of diffuse large B cell lymphoma in IPI low-risk group, but not in intermediate- and high-risk groups

2012 ◽  
Vol 97 (1) ◽  
pp. 98-102 ◽  
Author(s):  
Rika Kihara ◽  
Tomoyuki Watanabe ◽  
Takahiro Yano ◽  
Naokuni Uike ◽  
Seiichi Okamura ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Risk Group ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Low Risk ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Prognostic Impact of Germinal Center–Associated Proteins and Chromosomal Breakpoints in Poor-Risk Diffuse Large B-Cell Lymphoma

2006 ◽  
Vol 24 (25) ◽  
pp. 4135-4142 ◽  
Author(s):  
Gustaaf W. van Imhoff ◽  
Evert-Jan G. Boerma ◽  
Bronno van der Holt ◽  
Ed Schuuring ◽  
Leo F. Verdonck ◽  
...  
Keyword(s):  
B Cell ◽  
Expression Profile ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Prognostic Impact ◽  
Poor Risk ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose Outcome of diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) expression profile is superior to that of non-GCB DLBCL. This conclusion is mainly derived from patients with mixed international prognostic index (IPI) risk profiles treated with CHOP-like therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone). We wondered whether the prognostic impact of the expression profile would hold out in a homogeneous cohort of poor-risk DLBCL patients treated with high-dose sequential therapy (HDT) and autologous stem-cell transplantation (ASCT) as first-line therapy. Patients and Methods DLBCL from 66 newly diagnosed poor-risk patients, treated in two sequential prospective Dutch Hemato-Oncology Association (HOVON) trials, were studied retrospectively for expression of CD10, bcl6, MUM1/IRF4, bcl2, Ki67, and CD21+ follicular dendritic cells (FDC) by immunohistochemistry, and for the breakpoints of BCL2, BCL6, and MYC by fluorescent in situ hybridization (FISH). Lymphomas with any follicular component were excluded. Results A GCB immunophenotype profile was found in 58% and non-GCB immunophenotype profile in 42% of the tumors. Clinical characteristics of both groups were similar. Complete response (CR) rate was higher in patients with CD10+ tumors (58% v 30%; P = .03). A GCB immunophenotype profile, its constituting markers CD10 more than 30% and MUM1 less than 70%, and bcl2 less than 10% were each associated with a better overall survival (OS). FDC networks, equally present in GCB and non-GCB tumors, had superior CR (73% v 31%; P = .01), but disease-free survival rates were lower and there was no difference in OS rates. None of the breakpoints had a prognostic impact on outcome. Conclusion Also in patients with poor-risk DLBCL treated with HDT and ASCT, the GCB immunophenotype and bcl2 expression retained a major impact on survival.

Conditional Survival of Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1911-1911
Author(s):  
Michael B. Moller ◽  
Niels T. Pedersen ◽  
Bjarne E. Christensen
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Prognostic Impact ◽  
Conditional Survival ◽  
Large B Cell Lymphoma ◽  
The Individual ◽  
The Impact ◽  
Large B Cell

Abstract Purpose: Prognosis of lymphoma patients is usually estimated at the time of diagnosis, and the estimates are guided by the International Prognostic Index (IPI). However, survival rates calculated at the time of diagnosis may not be predictive of outcome for patients who have survived 1 or more years. For these patients conditional survival is more informative as only those patients who have already survived a period of time after treatment are considered. Conditional survival data have not been reported for lymphoma patients and the impact of the IPI on conditional survival is not known. Patients and Methods: Conditional survival was estimated for 1,209 patients with diffuse large B-cell lymphoma from the population-based LYFO-registry of the Danish Lymphoma Group. The patients were diagnosed between 1983 and 1998 with a median follow-up time of 7.8 years, and all patients were treated with curative intent. The Kaplan-Meier method was used to estimate conditional survival at 0–5 years after diagnosis. Results: The probability of surviving 5 years increased with each year survived for the first 3 years after diagnosis (from 43% to 70%) after which the increase was minimal (Figure 1). The median survival increased from 38 months for all patients to between 108 and 120 months conditioned on survival for at least 3 to 5 years. The distribution of patients in the IPI risk groups changed significantly over time. However this effect was only seen in the first 5 years. At diagnosis, 28% of the patients were allocated to the high-intermediate and high-risk groups, but only 11% of patients who survived 5 years were from these risk groups (P < .0001). Risk group allocation did not change the following 5 years (P = .7747). At the time of diagnosis overall survival differed greatly between the IPI risk groups (P < .0001; figure 2). However, 5 years after diagnosis the rates were similar (P = .0586). Furthermore, the prognostic impact of the individual clinical variables of the IPI (age, stage, performance score, LDH, and extranodal disease) was also significant at diagnosis, but 2 years after diagnosis only age had prognostic impact. Multivariate analysis (including the IPI and the individual IPI variables) of patients who survived ≥3 years identified only age as a prognostic factor (relative risk 4.1; P < .001). Conclusion: For patients with diffuse large B-cell lymphoma who have survived more than 1 year after diagnosis, the conditional survival probability provides more accurate prognostic information than the conventional survival rate estimated from the time of diagnosis. Furthermore, age is the most important factor for long-term survival, whereas the remaining IPI factors are not informative. Figure Figure Figure Figure

Does Rituximab Influence the Prognostic Effect of Germinal Centre Phenotype in Diffuse Large B-Cell Lymphoma?.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2743-2743 ◽  
Author(s):  
Heidi Nyman ◽  
Marja-Liisa Karjalainen-Lindsberg ◽  
Minna Taskinen ◽  
Mattias Berglund ◽  
Magdalena Adde ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Positive Impact ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Germinal Centre ◽  
Control Group ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract PURPOSE: Germinal centre (GC) and non-GC phenotypes are predictors of outcome in diffuse large B-cell lymphoma (DLBCL), and can be used to stratify chemotherapy-treated patients into low- and high-risk groups. Our aim was to determine how combination of rituximab with chemotherapy influences GC-associated clinical outcome. METHODS: 95 DLBCL patients treated with rituximab in combination with CHOP or CHOEP regimen (immunochemotherapy) were included in the study. The median follow-up time was 27 months. 107 patients previously treated with chemotherapy served as a historical control group. BCL-6, CD10, and MUM1 expression was analyzed immunohistochemically by means of identifying GC and non-GC phenotypes. In addition, BCL-2 expression was determined. Expression data was correlated with survival parameters. RESULTS: Consistent with previous studies, chemotherapy-treated patients with GC phenotype displayed a significantly better overall survival (OS) than the non-GC group (70% vs 47% p=0.012). In contrast, GC-phenotype did not predict outcome in immunochemotherapy-treated patients. The OS for GC-group was 82% compared with 80% for those with non-GC phenotype (p=ns). Conversely, the relapse free survival (RFS) for patients with GC and non-GC phenotypes were 74% and 65% (p=ns), respectively. When the patients were grouped according to BCL-2 expression, survival rates among the group of BCL-2 negative patients tended to be better than in BCL-2 positive patients (OS, 94% vs 77%, p=0.097; RFS, 94% vs 66%, p=0.029). CONCLUSIONS: Rituximab in combination with chemotherapy seems to interfere with the prognostic value of GC- and non-GC phenotypes in DLBCL. However, rituximab may have a positive impact on outcome among the patients with BCL-2 negativity.

The t(14;18) Is Associated with Germinal Center Phenotype Subset of the Diffuse Large B-Cell Lymphoma Patients in Egypt.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4124-4124
Author(s):  
Hasan A. Abdel-Ghaffar ◽  
Sherin M. Abdel-Aziz ◽  
Doaa A. Shahin ◽  
Ezzat S. Sobki Board ◽  
Nadia I. Attwan ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Biological Variables ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is a generic term for clinically and biologically heterogeneous group of tumors. Identification of high risk patients at presentation will allow effective trials of treatment. Therefore, t(14;18) detection using interphase Florescence in Situ Hybridization (FISH) and Biomed multiplex polymerase chain reaction (PCR) was done on formalin fixed paraffin embedded lymph node archives from pathology department, National Cancer Institute, Cairo, Egypt. Diagnosis were confirmed by pathological review using the diagnostic criteria defined in the revised European-American Classification of Lymphoid Neoplasm / WHO classification. The study was carried out on 26 patients with lymph screen CD 19 +/ CD 5 - / CD 10 ± correlating t(14;18) with the immunophenotypic biological variables, Immunohistochemistry, and the standardized international prognostic index (IPI) with a median follow up for 5 years. Comparison of FISH and PCR techniques showed identical specificity with advantageous sensitivity of FISH over the PCR. Nine patients out of eleven with t(14;18) were associated with Germinal Center (GC) phenotype (CD10+ /Bcl-6 +). However, Only two out of fifteen with non GC phenotype(CD10- /Bcl-6 -) were associated t(14;18). The mean 5 years survival time of patients with t(14;18) was significantly lower (31.18 ± 3.06 month) compared to those without translocation (54.32 ± 2.54 month) (P=0.001). Interestingly, patients with t(14;18) showed Bcl-2 positive (100%) compared to 46.6% in patient without t(14;18) (P=0.004). There is a significant correlation between t(14;18) and the clinicopathological risk criteria of IPI(P=0.01). In our study we demonstrated a detection of t(14;18) by FISH was found to be superior to PCR. The high risk group of GC phenotype together with Bcl-2 expression were associated with t(14;18) and could be used to tailor treatment.

scholarly journals Bcl-2 protein frequency in patients with high-risk diffuse large B-cell lymphoma

2010 ◽  
Vol 128 (1) ◽  
pp. 14-17 ◽  
Author(s):  
Abrahão Elias Hallack Neto ◽  
Sheila Aparecida Coelho Siqueira ◽  
Frederico Luiz Dulley ◽  
Alfredo Chauobah ◽  
Marcelo Belesso ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9%) were GCB-like and 49 (67.1%) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37%) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37% of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.

Prognostic impact of immunohistochemically defined germinal center B-cell and nongerminal center B-cell subtypes of diffuse large B-cell lymphoma in rituximab era.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18517-e18517
Author(s):  
Yabing Cao ◽  
Ying Huang ◽  
Sheng Ye ◽  
Tongyu Lin
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Survival Data ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Large B Cell

e18517 Background: Diffuse large B-cell lymphoma (DLBCL) can be molecularly subtyped as either germinal center B-cell (GCB) or non-GCB. The role of rituximab(R) in these two groups remains unclear. Methods: We studied 204 patients with de novo DLBCL (107 treated with CHOP; 97 treated with R-CHOP); patients being stratified into GCB and non-GCB on the basis of BCL-6, CD10 and MUM1 protein expression. The relationships between clinical characteristics, survival data and immunophenotype were studied. Results: The median follow-up was 51months for CHOP group and 56 months for R-CHOP group. The 5-year overall survival (OS) in the CHOP and R-CHOP group was 50.4% and 66.6% (p=0.031), respectively. GCB patients had a better 5-year OS than non-GCB patients whether treated with CHOP (65.0% vs. 40.9%; p=0.011). In contrast, there’s no difference in the 5-year OS for the GCB and non-GCB with R-CHOP (76.5% vs. 61.3%; p=0.141). In non-GCB subtype, additional rituximab improved survival than CHOP (61.3% vs. 40.9%; p=0.0303). Conclusions: These results indicated that addition of rituximab to standard chemotherapy eliminate the prognostic value of immunohistochemically defined GCB and non-GCB phenotypes in DLBCL by improving the prognostic value of non-GCB subtype of DLBCL

Addition of Rituximab to Standard Chemotherapy Improves the Survival of Both the Germinal Center B-Cell–Like and Non–Germinal Center B-Cell–Like Subtypes of Diffuse Large B-Cell Lymphoma

2008 ◽  
Vol 26 (28) ◽  
pp. 4587-4594 ◽  
Author(s):  
Kai Fu ◽  
Dennis D. Weisenburger ◽  
William W.L. Choi ◽  
Kyle D. Perry ◽  
Lynette M. Smith ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Control Group ◽  
Standard Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Large B Cell

Purpose Diffuse large B-cell lymphoma (DLBCL) includes at least two prognostically important subtypes (ie, germinal center B-cell–like [GCB] and activated B-cell–like [ABC] DLBCL), which initially were characterized by gene expression profiling and subsequently were confirmed by immunostaining. However, with the addition of rituximab to standard chemotherapy, the prognostic significance of this subclassification of DLBCL is unclear. Patients and Methods We studied 243 patient cases of de novo DLBCL, which included 131 patient cases treated with rituximab plus standard chemotherapy (rituximab group) and 112 patient cases treated with only standard chemotherapy (control group). The cases were assigned to GCB or non-GCB subgroups (the latter of which included both ABC DLBCL and unclassifiable DLBCL) on the basis of immunophenotype by using the Hans method. Clinical characteristics and survival outcomes of the two patient groups were compared. Results The clinical characteristics of the patients in the rituximab and the control groups were similar. Compared with the control group, addition of rituximab improved the 3-year overall survival (OS; 42% v 77%; P < .001) of patients with DLBCL. Rituximab-treated patients in either the GCB or the non-GCB subgroups also had a significantly improved 3-year OS compared with their respective subgroups in the control group (P < .001). In the rituximab group, the GCB subgroup had a significantly better 3-year OS than the non-GCB subgroup (85% v 69%; P = .032). Multivariate analyses confirmed that rituximab treatment was predictive for survival in both the GCB and the non-GCB subgroups. Conclusion In this retrospective study, we have shown that the subclassification of DLBCL on the basis of the cell of origin continues to have prognostic importance in the rituximab era.

scholarly journals In situ transcriptional profile of a germinal center plasmablastic burst hints at an unfavorable Diffuse Large B-cell Lymphoma subset.

2021 ◽  
Author(s):  
Vincenzo L'Imperio ◽  
Gaia Morello ◽  
Valeria Cancila ◽  
Giorgio Bertolazzi ◽  
Saveria Mazzara ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Functional Differentiation ◽  
Cytokine Signaling ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

The germinal center (GC) reaction results in the selection of B-cells acquiring effector Ig secreting ability by progressing towards plasmablastic differentiation. This transition is associated with exclusion from the GC microenvironment. The aberrant expansion of plasmablastic elements within the GC fringes configures an atypical condition, the biological characteristics of which have not been defined yet. We investigated the in situ immunophenotypical and transcriptional characteristics of a non-clonal germinotropic expansion of plasmablastic elements (GEx) occurring in the tonsil of a young patient. Compared to neighboring GC and peri-follicular regions, the GEx showed a distinctive signature featuring key regulators of plasmacytic differentiation, cytokine signaling, and cell metabolism. The GEx signature was tested in the setting of diffuse large B-cell lymphoma (DLBCL) as a prototypical model of lymphomagenesis encompassing transformation at different stages of GC and post-GC functional differentiation. The signature outlined DLBCL clusters with different overall survival, highlighting the negative prognostic impact of the overexpression of hallmark genes of this peculiar condition.

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