Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Lluı́s Colomo ◽  
Armando López-Guillermo ◽  
Marı́a Perales ◽  
Susana Rives ◽  
Antonio Martı́nez ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Clinicopathological Features ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract To analyze the relationship between immunophenotyping profile and main clinicopathological features and outcome in diffuse large B-cell lymphoma (DLBCL), we studied 128 patients (59 men, 69 women; median age 65 years) consecutively diagnosed with de novo DLBCL in a single institution. Cells from each patient were immunostained with CD20, CD79a, CD5, CD10, bcl-6, MUM1, CD138, bcl-2, p53, p27, and Ki-67 antibodies. Four immunophenotyping profiles were distinguished according to the pattern of differentiation: germinal center–CD10+ (GC-CD10+; CD10+/Bcl-6+/MUM1−/CD138−), germinal center–CD10− (GC-CD10−; CD10−/Bcl-6+/ MUM1−/CD138−), post–germinal center (pGC; CD10−/bcl-6±/ MUM1+/CD138−), and plasmablastic (CD10−/bcl-6−/MUM1+/CD138+). Rearrangement of bcl-2 was studied by polymerase chain reaction (PCR) in 57 patients. Single-antigen expression was as follows: CD5, 2%; CD10, 21%; bcl-6, 72%; MUM1, 54%; CD138, 2%; bcl-2, 59%; p53, 28%; p27, 40%. Distribution according to differentiation profiles was as follows: GC-CD10+, 24 patients, GC-CD10-, 30 patients; pGC, 60 patients; plasmablastic, 2 patients; other patterns, 12 patients. The pGC profile was associated with primary nodal presentation and immunoblastic morphology, whereas GC-CD10+ tumors showed disseminated disease, centroblastic morphology, bcl-2 rearrangement, and lower Ki-67 proliferative index. GC-CD10− patients more often presented with primary extranodal origin, early stage, normal lactic acid dehydrogenase (LDH) levels, and low or low/intermediate International Prognostic Index (IPI) scores than the others. However, no significant difference was found in terms of response or overall survival (OS) according to these profiles. Expression of bcl-2 was associated with advanced stage, high or high-intermediate IPI, and poor OS. Expression of bcl-2 maintained predictive value in multivariate analysis, with stage and LDH. In conclusion, differentiation profile was associated with particular clinicopathological features but was not essential to predicting outcome in DLBCL patients.

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.

Comparison Between CD20-Negative and CD20-Positive Diffuse Large B Cell Lymphoma; Characteristics and Clinical Outcome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4891-4891
Author(s):  
Jungmin Jo ◽  
Changhoon Yoo ◽  
Yongchel Ahn ◽  
Seong Joon Park ◽  
Shin Kim ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Risk Group ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract Abstract 4891 Background CD20 is a non-glycosylated phosphoprotein expressed on the surface of all mature B-cells. CD20 is expressed on all stages of B cell development except the first and last. However, complete lack of CD20 expression occurred in a few cases without previous rituximab (R-) treatment. The immunohistochemostry (IHC) studies which we used were not perfect for confirmation of expression. However, we intended to investigate characteristics and clinical outcome of CD20-negative diffuse large B-cell lymphoma (DLBCL), not detected with usual method, and to compare with CD20-positive. Methods The records of Non-Hodgkin's Lymphoma patient registry were reviewed in Asan Medical Center. Between September 2003 and February 2009, a total of 407 patients were diagnosed DLBCL and 16 patients (3.9%) out of 407 confirmed CD20-negative DLBCL by IHC. The rest of patients (n=391) were CD20-positive and unconfirmed cases were excluded. Retrospective analysis of complete response (CR), disease-free survival (DFS), and overall survival (OS) was performed. Results The median age was 60.5 years old (range 31–81) in CD20-negative patients. Ten patients were males. The Ann Arbor stage was I in 3 patients, II in 3 patients, and III or IV in 10. Six patients were low risk group, 7 patients in intermediate, and 3 in high risk group according to international prognostic index (IPI). Most of patients (62.5%) received cyclophosphamide, doxorubicin, vincristin, and prednisone (CHOP) chemotherapy in CD20-negative and 295 patients (75.4%) with R-CHOP in CD20-positive DLBCL. The Baseline characteristics was not different in both groups except Hans classifier (p=0.02). With a median follow-up time of 32.3 months (range 0.5–83.4), the CR rate was 73.5%, the 3-year OS was 69.5%, and 3-year DFS 74.2% in all patients. CD20-positive and CD20 negative groups had a CR rate of 73.7%, 68.8% (p=0.146), respectively, a 3-year OS of 70.7%, 40.0% (p=0.003), a 3-year DFS of 75.4%, 44.6% (p< 0.001), respectively. The 3-year OS and DFS also had significant difference with adjusted IPI (p<0.001, respectively). Conclusions CD20-negaive DLBLC was not infrequently with usual IHC method (around 4%). The survival outcome was poor compared with CD20-positive DLBLC because of high relapse rate. It was caused without rituximab treatment in CD20-negative. Development of novel target agents like rituximab should be explored to improve outcome and maintain the CR status of CD20-negative DLBCL. Disclosures: No relevant conflicts of interest to declare.

Fas or Fas Ligand Expression Can Determine the Clinical Outcome of Germinal Center Type in Diffuse Large B Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3267-3267
Author(s):  
Yasushi Kojima ◽  
Hisashi Tsurumi ◽  
Naoe Goto ◽  
Michio Sawada ◽  
Toshiki Yamada ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Germinal Center ◽  
Fas Ligand ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Type 3 ◽  
Large B Cell

Abstract In recent years, diffuse large B cell lymphoma (DLBCL) has been classified by a cDNA microarray, an oligonucreotide microarray, or a tissue microarray. From the prognostic point of view, DLBCL consists of germinal center B-cell-like (GC) type, activated B-cell-like (ABC) type and type 3. ABC type and type 3 can be collectively categorized as non-GC (NGC) type. GC type has favorable prognosis compared with NGC type. Escape from apoptosis is considered to be an important mechanism for the progression of lymphoma. Fas is the major protein which leads to apoptosis by binding with Fas-ligand (FasL). We evaluated the prognostic significance of such markers as CD10, Bcl-6, MUM1, Fas and FasL, as well as GC or NGC type with paraffin embedded sections from 69 DLBCL patients immunohistochemicaly. The patients were 40 men and 29 women with median age of 67 years old (range, 20–82 years old). The median follow-up of surviving patients was 43 months. The 3-year OS for the entire group was 56%. There was no significant difference in sex, age, clinical stage, lactate dehydrogenase, or International Prognostic Index between GC and NGC type. Expression of CD10 was seen in 29% (20 of 69 of the patients), Bcl-6 in 27% (19 of 69), MUM1 in 27% (19 of 69), Fas in 51% (36 of 69), and FasL in 50% (35 of 69). We divided 69 DLBCLs to 26 GC type (CD10 positive or Bcl-6 positive and MUM1 negative) and 43 NGC type (the other). Positive CD10 was the best marker to indicate favorable overall survival (p=0.0156). GC type had tendency to have better overall survival than NGC type, though it was not significant (p=0.0723). Although Fas or FasL expression was not significant for overall survival in all DLBCL, it predicted significantly a longer over all survival (Fas; p=0.0021, FasL; p=0.0165) in GC type. These results may suggest that the presence of a subtype of DLBCL in which Fas/FasL system works effectively. This group is approximately 20% of DLBCL and mainly belongs to the GC type. Fas expression in GC type of DLBCL may predict the prognosis and be useful to choose the appropriate therapy. Furthermore, CD10 was more significant than GC type and, thus, we may need to build the strict consensus for GC type.

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.

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.

scholarly journals CD5-Positive Marginal Zone Lymphoma: Clinicopathological Features And Survival Outcomes

2021 ◽  
Author(s):  
Yaqin Xia ◽  
Jurui Ge ◽  
Zhenchang Sun ◽  
Feifei Nan ◽  
Wenjuan Wan ◽  
...  
Keyword(s):  
B Cell ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Marginal Zone Lymphoma ◽  
Clinicopathological Features ◽  
Survival Outcomes ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Large B Cell

Abstract Background: CD5 expression in diffuse large B-cell lymphoma has a poor prognosis but the prognostic value of CD5 expression in marginal zone lymphoma is undefined. Methods: Clinicopathological features, survival outcomes, and prognostic implications of marginal zone lymphoma were retrospectively analyzed in 204 patients. We classified patients into (i) CD5-positive marginal zone lymphoma (ii) CD5-negative marginal zone Lymphoma, Fisher's exact test was used to compare the CD5-positive and CD5-negative marginal zone lymphoma. Progression-free survival (PFS) and overall survival (OS) curves were summarized by Kaplan-Meier method and compared using the log-rank test, The Cox proportional hazard regression model was used for univariate and multivariate analyses. Results: CD5 expression is rare in marginal zone lymphoma, of 204 patients, only 48 (23.53%) had CD5-positive. Due to the characterized of slow growth and locally aggressive nature, the prognosis is favorable after treatment. at the end of the followup 179 patients were still alive,163 patients never progressed. The 5-year PFS and OS rates for marginal zone lymphoma were 65.10% and 77.30% respectively, the 5-year PFS and OS rates for CD5-positive marginal zone lymphoma were 64.80% and 84.10%, there is no significant difference between CD5-positive and CD5-negative ( P =0.829, P =0.521). Diffuse large B-cell lymphoma (DLBCL) transformation was pathologically indicated in 6 patients, of which 5(83.33%) patients were CD5-positive marginal zone lymphoma. Conclusion: CD5 expression in marginal zone lymphoma is not independently prognostic for PFS and OS. But CD5-positive marginal zone lymphoma seems more likely to transformation to diffuse large B-cell lymphoma.

scholarly journals BCL2/Ki-67 index predict survival in germinal center B-cell-like diffuse large B-cell lymphoma

2017 ◽  
Vol 14 (3) ◽  
pp. 3767-3773 ◽  
Author(s):  
Yun-Long Tang ◽  
Yan Zhou ◽  
Ling-Ling Cheng ◽  
Yong-Zhong Su ◽  
Chun-Bin Wang
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Large B Cell

Young Patients With Non–Germinal Center B-Cell–Like Diffuse Large B-Cell Lymphoma Benefit From Intensified Chemotherapy With ACVBP Plus Rituximab Compared With CHOP Plus Rituximab: Analysis of Data From the Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association Phase III Trial LNH 03-2B

2014 ◽  
Vol 32 (35) ◽  
pp. 3996-4003 ◽  
Author(s):  
Thierry Jo Molina ◽  
Danielle Canioni ◽  
Christiane Copie-Bergman ◽  
Christian Recher ◽  
Josette Brière ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Young Patients ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Large B Cell

Purpose To determine whether any tumor biomarkers could account for the survival advantage observed in the LNH 03-2B trial among patients with diffuse large B-cell lymphoma (DLBCL) and low-intermediate risk according to the International Prognostic Index when treated with dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) compared with standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP). Patients and Methods Using immunohistochemistry, expression of CD10, BCL6, MUM1, MYC, and BCL2 and coexpression of MYC/BCL2 were examined. The interaction effects between each biomarker and treatment arm on survival were studied in a restricted model and a full model incorporating clinical parameters. Results Among the 379 patients analyzed in the trial, 229 tumors were evaluable for germinal center B-cell–like (GCB)/non-GCB subclassification according to the Hans algorithm. Among all the biomarkers, only the interaction between the Hans algorithm and the treatment arm was significant for progression-free survival (PFS) and overall survival (OS) in univariable (PFS, P = .04; OS, P = .01) and multivariable (PFS, P = .03; OS, P = .01) analyses. Non-GCB tumors predicted worse PFS (hazard ratio [HR], 3.21; 95% CI, 1.29 to 8.00; P = .01) and OS (HR, 6.09; 95% CI, 1.37 to 27.03; P = .02) among patients treated with R-CHOP compared with patients who received R-ACVBP, whereas there were no significant survival differences between these regimens among patients with GCB tumors. Conclusion The survival benefit related to R-ACVBP over R-CHOP is at least partly linked to improved survival among patients with non-GCB DLBCL. Therefore, the Hans algorithm could be considered a theragnostic biomarker for selecting young patients with DLBCL who can benefit from an intensified R-ACVBP immunochemotherapy regimen.

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