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

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

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ying Huang ◽  
Sheng Ye ◽  
Yabing Cao ◽  
Zhiming Li ◽  
Jiajia Huang ◽  
...  

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. We studied 204 patients with de novo DLBCL (107 treated with first-line CHOP; 97 treated with first-line 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 (IHC) were studied. The 5-year overall survival (OS) in the CHOP and R-CHOP groups 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 or not (65.0% versus 40.9%;P=0.011). In contrast, there is no difference in the 5-year OS for the GCB and non-GCB with R-CHOP (76.5% versus 61.3%;P=0.141). In non-GCB subtype, additional rituximab improved survival better than CHOP (61.3% versus 40.9%;P=0.0303). These results indicated that addition of rituximab to standard chemotherapy eliminates the prognostic value of IHC-defined GCB and non-GCB phenotypes in DLBCL by improving the prognostic value of non-GCB subtype of DLBCL.


2017 ◽  
Vol 35 (31) ◽  
pp. 3538-3546 ◽  
Author(s):  
John P. Leonard ◽  
Kathryn S. Kolibaba ◽  
James A. Reeves ◽  
Anil Tulpule ◽  
Ian W. Flinn ◽  
...  

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.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18531-18531
Author(s):  
W. Kim ◽  
Y. Oh ◽  
C. Park

18531 Background: Diffuse large B cell lymphoma (DLBCL) can be subdivided into germinal center B cell-like (GCB) and non- germinal center B cell-like (Non-GC) types by immunohistochemical profiling. Previous studies showed better survival rate for the GCB groups. CD44 is necessary for tumor spread and metastasis and its expression is generally associated with unfavorable prognosis. We analyzed the expression and prognostic significance of standard isoform CD44s and its variant isoform CD44v6 in DLBCL types. Methods: Tissue microarray blocks were created from 52 nodal DLBCL with control tissue. Immunohistochemical staining for CD10, Bcl-6, MUM-1, CD44s, and CD44v6 were performed. The median follow-up period was 44 months. Results: Nodal DLBCLs were subclassified into GCB [CD10+ or CD10-/Bcl6+/MUM1+, n=17 (33%)] and non-GC subgroups [CD10-/Bcl6- or CD10-/Bcl6+/MUM1+, n=35 (67%)]. CD44s expression appeared more on non-GC cases of DLBCL (p=0.04). CD44s and CD44v6 did not result in any difference according to tumor stage, IPI scores, LDH levels. Upon survival analysis, CD44s and CD44v6 expression did not show any statistical correlation. Conclusions: CD44s expression may play a role during lymphomatogenesis of non-GC type DLBCL. No significant financial relationships to disclose.


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 ◽  
...  

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.


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