The Germinal Center/Activated B-Cell Subclassification Has a Prognostic Impact for Response to Salvage Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Bio-CORAL Study

2011 ◽  
Vol 29 (31) ◽  
pp. 4079-4087 ◽  
Author(s):  
Catherine Thieblemont ◽  
Josette Briere ◽  
Nicolas Mounier ◽  
Hans-Ullrich Voelker ◽  
Wendy Cuccuini ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose To evaluate the prognostic value of the cell of origin (COO) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBLC), prospectively treated by rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) versus rituximab, ifosfamide, carboplatin, and etoposide and followed by intensive therapy plus autologous stem-cell transplantation on the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) trial. Patients and Methods Among the 396 patients included on the trial, histologic material was available for a total of 249 patients at diagnosis (n = 189 patients) and/or at relapse (n = 147 patients), which included 87 matched pairs. The patient data were analyzed by immunochemistry for CD10, BCL6, MUM1, FOXP1, and BCL2 expression and by fluorescent in situ hybridization for BCL2, BCL6 and c-MYC breakpoints. The correlation with survival data was performed by using the log-rank test and the Cox model. Results Characteristics of immunophenotype and chromosomal abnormalities were statistically highly concordant in the matched biopsies. In univariate analysis, the presence of c-MYC gene rearrangement was the only parameter to be significantly correlated with a worse progression-free survival (PFS; P = .02) and a worse overall survival (P = .04). When treatment interaction was tested, the germinal center B (GCB) –like DLBCL that was based on the algorithm by Hans was significantly associated with a better PFS in the R-DHAP arm. In multivariate analysis, independent prognostic relevance was found for the GCB/non-GCB the Hans phenotype interaction treatment (P = .04), prior rituximab exposure (P = .0052), secondary age-adjusted International Prognostic Index (P = .039), and FoxP1 expression (P = .047). Confirmation was obtained by gene expression profiling in a subset of 39 patients. Conclusion COO remains a major and independent factor in relapsed/refractory DLBCL, with a better response to R-DHAP in GCB-like DLBCL. This needs confirmation by a prospective study.

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.

Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non–Germinal Center B-Cell–Like Diffuse Large B-Cell Lymphoma

2017 ◽  
Vol 35 (31) ◽  
pp. 3538-3546 ◽  
Author(s):  
John P. Leonard ◽  
Kathryn S. Kolibaba ◽  
James A. Reeves ◽  
Anil Tulpule ◽  
Ian W. Flinn ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
The Impact ◽  
Large B Cell

Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non–germinal center B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

scholarly journals Hypoxia-Inducible Factor-1 α Expression Predicts Superior Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP

2010 ◽  
Vol 28 (6) ◽  
pp. 1017-1024 ◽  
Author(s):  
Andrew M. Evens ◽  
Laurie H. Sehn ◽  
Pedro Farinha ◽  
Beverly P. Nelson ◽  
Adekunle Raji ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Hypoxia Inducible Factor ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Wide Range ◽  
Large B Cell

Purpose Hypoxia-inducible factor (HIF) controls the expression of genes in response to hypoxia, as well as a wide range of other cellular processes. We previously showed constitutive stabilization of HIF-1α in the majority of patients with diffuse large B-cell lymphoma (DLBCL). To our knowledge, the prognostic significance of HIF in lymphoma has never been investigated. Patients and Methods We studied the immunohistochemical protein expression of HIF-1α on tissue microarrays from 153 patients with DLBCL treated in sequential cohorts with cyclophosphamide, doxorubicin, oncovin, and prednisone (CHOP) or rituximab-CHOP (R-CHOP) from 1999 to 2002. Results were correlated with patient outcome. Results Median follow-up for all patients was 80 months. Among all patients, HIF-1α was expressed in 62% of germinal center and 59% of non–germinal center patients. With HIF-1α analyzed as a dependent variable, there were no survival differences in CHOP-treated patients. In the R-CHOP group, however, HIF-1α protein expression correlated with significantly improved progression-free survival (PFS) and overall survival (OS). Five-year PFS for HIF-1α–positive patients was 71% v 43% for HIF-1α–negative patients (P = .0187), whereas 5-year OS was 75% and 54%, respectively (P = .025). In multivariate analysis with International Prognostic Index criteria, HIF-1α remained a significant predictor for PFS (P = .026) and OS (P = .043). Compared with other biomarkers, HIF-1α correlated only with BCL6 (P = .004). In terms of gene expression, we found several common gene associations of HIF-1α and the stromal-1 signature with genes predominantly involved in regulation of the extracellular matrix (eg, BGN, COL1A2, COL5A1, and PLOD2). Conclusion The expression of HIF-1α protein is an important independent favorable prognostic factor for survival in patients with DLBCL treated with R-CHOP.

Immunohistochemical Expression Pattern of Germinal Center and Non-Germinal Center Markers Correlates with Prognosis in Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4636-4636
Author(s):  
Carlos Chiattone ◽  
Marineide P. Carvalho ◽  
Roberto P. Paes ◽  
Karina C.B. Ribeiro ◽  
Fernando Soares
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Immunohistochemical Expression ◽  
Molecular Features ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Recent studies have shown correlations between diffuse large B-cell lymphoma (DLCBL) prognosis and molecular features using genome profiles by cDNA microarrays. Since this analysis is not routinely used, immunohistochemical tests for prediction of DLBCL survival are gaining major importance, using markers as, CD10, BCL-6 and MUM-1 to identify germinal center B-cell (GCB) and non-GCB, respectively. The goal of this study was to evaluate the significant effect on survival within GCB and non-GCB subgroup. Patients and Methods: Seventy-four untreated pts (median age: 58 yrs: 38M/36F) with DLBCL de novo diagnosed in a single institution, treated with CHOP-like regimens. Tissue microarrays (TMA) blocks were created from paraffin-embedded, formalin-fixed block and stained with antibodies to CD20 (clone L26, Dako), CD10 (clone 56C6; Novocastra; NCL-CD10-270), BCL-6 (clone GI 191E/A8; Cell Mark; CMC 798) and MUM1 (clone MUM1p; Dako, CA; M7259). Results. Cases were subclassified using CD10, BCL-6, and MUM1 expression, and 25 cases (33.8%) were considered GCB and 49 cases (66.2%) non-GCB. The 2-year overall survival (OS) for the GCB group was 80% compared with only 38.9% for the non-GCB (p<0.001). In the multivariate analysis, only the International Prognostic Index score (IPI 3-4 HR=2.6, p=0.013) and the GCB phenotype (Non-GCB HR=2.7, p=0.054) were independent prognostic factors. In summary, immunohistochemical expression of CD10, BCL-6 and MUM1 are able to determine the GCB and non-GCB subtypes of DLBCL and predict survival.

Impact of Concordant and Discordant Bone Marrow Involvement on Outcome in Diffuse Large B-Cell Lymphoma Treated With R-CHOP

2011 ◽  
Vol 29 (11) ◽  
pp. 1452-1457 ◽  
Author(s):  
Laurie H. Sehn ◽  
David W. Scott ◽  
Mukesh Chhanabhai ◽  
Brian Berry ◽  
Anna Ruskova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Bone Marrow Biopsies ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose In diffuse large B-cell lymphoma (DLBCL), prior studies suggest that concordant bone marrow involvement with DLBCL portends a poorer prognosis, whereas discordant bone marrow involvement with small B-cell lymphoma does not. We examined the significance of bone marrow involvement in patients treated in the current era of therapy including rituximab. Patients and Methods We performed a retrospective analysis of the prognostic impact of bone marrow involvement in an unselected population of patients with newly diagnosed DLBCL treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in British Columbia and Auckland, New Zealand, with complete clinical information and evaluable staging bone marrow biopsies. Results In total, 795 patients were identified. Six hundred seventy (84.3%) of 795 had a negative bone marrow, 67 patients (8.4%) had concordant and 58 (7.3%) had discordant involvement. Median follow-up was 41 months (range, 1 to 115). Progression-free survival (PFS) was inferior in those with concordant (P < .001) and discordant (P = .019) involvement while overall survival (OS) was inferior in those with concordant involvement (P < .001) only. In a multivariate analysis controlling for the International Prognostic Index (IPI) score, concordant involvement remained an independent predictor of PFS (P < .001) and OS (P = .007). Discordant involvement was associated with older age, elevated lactate dehydrogenase, advanced stage, and increased number of extranodal sites and was not a negative prognostic factor independent of the IPI score. Conclusion The negative prognostic impact of discordant involvement is adequately represented by the IPI score, while the risk with concordant involvement is greater than that encompassed by this predictor. The results emphasize the need for accurate staging assessment of bone marrow involvement in DLBCL.

scholarly journals Low Absolute Lymphocyte Counts in the Peripheral Blood Predict Inferior Survival and Improve the International Prognostic Index in Testicular Diffuse Large B-Cell Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1967
Author(s):  
Pauli Vähämurto ◽  
Marjukka Pollari ◽  
Michael R. Clausen ◽  
Francesco d’Amore ◽  
Sirpa Leppä ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Prognostic Impact ◽  
Large B Cell Lymphoma ◽  
Increased Risk ◽  
Absolute Lymphocyte Counts ◽  
Large B Cell

Low absolute lymphocyte counts (ALC) and high absolute monocyte counts (AMC) are associated with poor survival in patients with diffuse large B-cell lymphoma (DLBCL). We studied the prognostic impact of the ALC and AMC in patients with testicular DLBCL (T-DLBCL). T-DLBCL patients were searched using Southern Finland University Hospital databases and the Danish lymphoma registry. The progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox proportional hazards methods. We identified 178 T-DLBCL patients, of whom 78 (44%) had a low ALC at diagnosis. The ALC did not correlate with survival in the whole cohort. However, among the patients treated with rituximab (R) containing regimen, a pre-therapeutic low ALC was associated with an increased risk of progression (HR 1.976, 95% CI 1.267–3.086, p = 0.003). Conversely, intravenous (iv) CNS directed chemotherapy translated to favorable outcome. In multivariate analyses, the advantage of an iv CNS directed chemotherapy was sustained (PFS, HR 0.364, 95% CI 0.175–0.757, p = 0.007). The benefit of R and intravenous CNS directed chemotherapy was observed only in non-lymphopenic patients. The AMC did not correlate with survival. A low ALC is an adverse prognostic factor in patients with T-DLBCL. Alternative treatment options for lymphopenic patients are needed.

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.

Prognostic Value of cMYC Gene Abnormalities in Diffuse Large B Cell Lymphoma Treated with Chemo-Immunotherapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2664-2664 ◽  
Author(s):  
Ana Batlle López ◽  
Sonia Glez de Villambrosia ◽  
Santiago Montes-Moreno ◽  
Francisco Mazorra ◽  
Andrés Insunza ◽  
...  
Keyword(s):  
Cancer Research ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2664 Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas. Despite improvements in diagnostic and therapeutic procedures, DLBCL still represents a significant cause of morbidity and mortality. Two molecularly defined types of DLBCL have been recently described: the germinal center B-cell (GCB) and the activated B-cell (ABC) subtype. GCB type DLBCL has been shown to have a better OS and PFS than ABC-type in multiple series of DLBCL patients treated with chemoimmunotherapy. The processes involved in lymphomagenesis in both subtypes are not fully understood, but deregulated expression of various proto-oncogenes is observed, often as the result of chromosomal translocations leading to constitutive gene expression. The specific role of the cMYC gene abnormalities in the pathogenesis of these lymphomas is still a matter of debate. To address this question, the status of the cMYC gene was analyzed by interphase fluorescence in situ hybridization (FISH) using a break apart probe, in TMA arranged tissue samples from 241 patients with de novo DLBCL treated with chemoimmunotherapy (R-CHOP and R-CHOP-like regimens). cMYC was rearranged in 15 cases out of 166 evaluable (9.26%). We did not find differences in the incidence of cMYC rearrangements between GCB and ABC-DLBCL subtypes (9/74 GCB and 6/82 ABC type) as classified according to extended immunohistochemical algorithms (Choi et al in Cancer Res. 2009). In our series, patients with DLBCL and cMYC rearrangements presented more frequently extranodal disease (p=0.007), higher IPI (p=0.037) and tended to have less than 60 years (p=0.053). cMYC gains were observed in 33 cases (21.85%). In the univariate analysis, cMYC abnormalities (gains and rearrangements) had no impact on the clinical outcome in the ABC subtype. However, whilst the cMYC gains did not identify a risk group in terms of OS or PFS the presence of cMYC rearrangements showed a significantly inferior progression-free survival (PFS) in the GCB-type group (p<0.006). However, the multivariate analysis showed that the only independent adverse predictors in these series of DLBCL cases were the presence of a high International Prognostic Index score (p=0.0028; RR=2.59 95% CI 1,34–4,99) and the ABC phenotype (p=0.0182; RR=2.16 95% CI 1,1–4,21). In summary, although cMYC rearrangements apparently do not provide additional prognostic information to the IPI score and/or GC-ABC classification in the whole DLBCL population, it identifies a subgroup of GCB-type DLBCL with very poor outcome. Disclosures: Montalban: Red Temática de Investigación Cooperativa en Cancer (RETICC): Research Funding; Asociación Española contra el Cancer: Research Funding. Mollejo:Red Temática de Investigación Cooperativa en Cancer (RETICC): Research Funding; Asociación Española contra el Cancer: Research Funding.

The t(14;18)(q32;q21) Characterizes a Subset of Patients with Diffuse Large-B Cell Lymphoma of Germinal Center Origin with Poor Outcome: Report From the International DLBCL Rituximab-CHOP Consortium Program Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 949-949 ◽  
Author(s):  
Carlo Visco ◽  
Alexander Tzankov ◽  
Zijun Y. Xu-Monette ◽  
Roberto N. Miranda ◽  
Emanuele S. G. d'Amore ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Individual Risk ◽  
Large B Cell Lymphoma ◽  
Bcl2 Protein ◽  
Large B Cell

Abstract Abstract 949 Introduction: Diffuse large B cell lymphoma (DLBCL) has a highly variable outcome, and individual risk assessment is largely based on clinical features. Gene expression profiling (GEP) stratifies patients into those with germinal center B-cell (GCB) and activated B-cell subtype (ABC) subtype with different prognoses. These groups have been shown to predict prognosis in patients treated with CHOP or R-CHOP. Conversely, the role of other recognized prognostic markers, such as BCL2 gene abnormalities or Bcl2 expression has been questioned in the new therapeutic era. Materials and Methods: In 438 patients treated with R-CHOP for de novo DLBCL, we analyzed the tumors by immunohistochemistry for Bcl2 protein expression and by interphase fluorescence in situ hybridization (FISH) for BCL2 translocation and other abnormalities. All cases were successfully studied by GEP. The cutoff for Bcl2 protein expression, 60%, used as prognostic factor was determined using receiver operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were assessed. Results: The t(14;18)(q32;q21) was detected in 82 cases (18.7%) and BCL2 gains occurred in 63 cases (14.3%). Both t(14;18) and BCL2 gains strongly correlated with higher levels of Bcl2 protein expression (p<0.0001 for both). Presence of t(14;18) was associated with the GCB subtype (p<0.0001), whereas BCL2 gains were associated with the ABC subtype (p=0.004). BCL2 gains were not predictive of PFS in any patients' subgroups. Conversely, within the GCB subtype, patients with the t(14;18) displayed a significantly worse outcome compared to GCB patients without t(14;18) with a 5-year PFS of 45% vs 68%, respectively (p<0.0001). Outcome of patients with DLBCL associated with t(14;18) was similar to patients with the ABC subtype (45% vs 48%, p=0.30, Figure 1). No impact of the t(14;18) and BCL2 gains was observed on patients with ABC-DLBCL. Using immunohistochemistry, patients with Bcl2 positive (>60%) tumors had significantly inferior PFS in the GCB subgroup (p=0.03), but not in the ABC subgroup (p=0.54). Multivariate analysis revealed that the presence of the t(14;18), but not Bcl2 protein expression, was independent of the International Prognostic Index in predicting outcome of our patients. Conclusions: Patients with the GCB subtype and t(14;18) exhibit a significantly worse prognosis than patients without t(14;18) when treated with R-CHOP. The assessment of t(14;18) by FISH approach not only functions as a valuable prognosticator for individual risk estimation in GCB-DLBCL patients in addition to the established parameters, but also provides valuable result for therapeutic intervention. Disclosures: No relevant conflicts of interest to declare.

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