Immunohistochemical Expression of CD10, BCL6, and MUM1 in Primary Nodal Diffuse Large B-Cell Lymphoma: MUM1 Expression Alone (but Not Germinal Center B-Cell Immunophenotype) Is an Independent Prognostic Factor.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4706-4706
Author(s):  
Nicholas Wongchaowart ◽  
Ena Segota ◽  
Tao Jin ◽  
Brad Pohlman ◽  
Eric D. Hsi
Keyword(s):  
B Cell ◽  
Disease Progression ◽  
Lower Risk ◽  
B Cell Lymphoma ◽  
Primary Therapy ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Risk Of Progression ◽  
Bcl6 Expression

Abstract Introduction: Diffuse large B-cell lymphoma (DLBL) is a biologically and clinically heterogeneous lymphoma. Gene expression profiling studies using cDNA microarray have led to the development of a new paradigm for the subclassification of DLBL into germinal center B-cell (GCB) and activated B-cell types with a favorable and an unfavorable prognosis, respectively. The expression pattern of CD10, BCL6 and MUM1 by immunohistochemistry (IHC) has been proposed as a surrogate to distinguish GCB from non-GCB types. This immunohistochemical model must be validated in other data sets. Methods: We identified 57 cases of primary nodal DLBL for which the initial diagnostic biopsy, International Prognostic Index (IPI), and clinical follow-up were available. These patients (pts) received CHOP (n=51) or CHOP-like (n=6) chemotherapy, rituximab (n=12), radiation therapy (n=20), and high dose therapy with stem cell transplantation (SCT)(n=6) as planned primary therapy with curative intent. A tissue microarray (TMA) was constructed and cases were assessed for expression of CD10, BCL6, and MUM1. GCB and non-GCB immunophenotypes (IP) were defined as previously described (Hans et al. Blood 2004, 103:272–85). Clinical endpoints were disease progression and death. Analyses were performed using Cox proportional hazards testing. Results: The pts consisted of 32 men and 25 women with median age of 60 (range 29–82) years. 26 pts progressed and 25 pts died. Median follow-up of surviving pts was 69.9 (range 8.3–148.1) months. 64%, 82%, and 58% of cases expressed CD10, BCL6, and MUM 1, respectively, and 69% had a GCB IP using the Hans criteria. Univariate analysis showed that high IPI and MUM1 expression predicted a higher risk of progression (P<.001 and P=.027) while IPI, MUM1, and GCB IP predicted a higher risk of death (P<.001, P=.031, and P=.023). BCL6 expression was associated with a trend toward a lower risk of progression (P=.10) but not death (P=.38). By multivariate analysis, high IPI and MUM1 expression remained independent predictors of both progression (HR 7.07, 95% CI 2.68–18.63, P<.001 and HR=3.88, 95% CI 1.51–9.95, P=.005, respectively) and death (HR 6.48, 95% CI 2.57–16.34, P<.001 and HR 3.21, 95% CI 1.25–825, P.015, respectively) while BCL6 expression predicted a lower risk of progression only (HR 0.29, 95% CI 0.11–0.74, P=0.01). Two re-analyses excluding pts that received rituximab or SCT as a planned part of primary therapy gave similar results. Conclusions: We were unable to confirm the significance of GCB vs non-GCB types using CD10, BCL6, and MUM1 immuhistochemical expression patterns as independent predictors of either progression or death in this cohort of nodal DLBL. However, MUM1 expression (in addition to high IPI) was an independent predictor of a higher risk of both disease progression and death. BCL6 was an independent predictor of a lower risk of disease progression. BCL6 and MUM1 assessment using IHC in nodal DLBL provides useful prognostic information and simplifies pathological risk stratification of nodal DLBL from 3 to 2 markers. These data require confirmation in a larger, independent cohort of nodal DLBL pts treated with a rituximab-containing chemotherapy regimen.

Surveillance PET-CT Scanning Is Useful in the First 18 Months Following Completion of Therapy for Patients with Diffuse Large B-Cell Lymphoma with IPI≥3.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2652-2652
Author(s):  
Chan Y Cheah ◽  
Michael S Hofman ◽  
Michael J. Dickinson ◽  
Andrew Wirth ◽  
David A Westerman ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
High Sensitivity ◽  
B Cell Lymphoma ◽  
Ct Scanning ◽  
Primary Therapy ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Large B Cell

Abstract Abstract 2652 Introduction Despite improvements in cure rates for patients with diffuse large B-cell lymphoma (DLBCL), up to 40% relapse after achieving initial remission, mostly within 18 months from treatment. There is no consensus as to role, or most appropriate form of post-remission surveillance. Our aim was to explore the role of Positron Emission Tomography combined with computer tomography (PET-CT) scanning in the follow up of patients with diffuse large B-cell lymphoma (DLBCL) achieving complete metabolic response (CMR) after primary therapy, identify patterns of relapse and define a risk-adapted strategy. Results We included 116 patients with de novo DLBCL treated at our centre between 2002 and 2009 with a negative post-treatment PET-CT, and at least one surveillance PET-CT scan. International Prognostic Index (IPI) was <3 in 77 (66%) and ≥3 in 37 (32%) patients. With a median follow up of 53 months (range 8–133), 456 surveillance scans were performed (range 1–10 per patient). 13 patients (11%) relapsed, with an actuarial 5 year relapse free survival of 86%. Two-thirds of relapses occurred in the first 18 months following completion of treatment. In seven cases (54%), the relapse was suspected based on symptoms and in six (46%) the relapse was subclinical and detected with PET. There was no difference in survival (P=0.76) or second line IPI (P=1.00) between the groups, as the number of relapses was small. PET-CT had very high sensitivity (100%), specificity (98%) and negative predictive value (NPV, 100%) with positive predictive value (PPV) 56% in the cohort of patients with a low IPI (<3) compared with 80% if the IPI was ≥3. Across the entire cohort, the average number of patients in remission needed to scan to detect one subclinical relapse within the first 18 months was 42. However, for those with an IPI ≥3 the number needed to scan to detect one subclinical relapse was 22. Surveillance PET-CT had a very low yield after 18 months had elapsed from the conclusion of primary therapy (1 true positive among 170 scans). Interim response PET-CT was performed in 81 (70%) patients; achieving CMR was not a predictor of time to relapse (P=0.65) or having a positive surveillance scan, irrespective of IPI (P=1.00). Second malignancies were detected by PET-CT in eight patients (7%). Conclusion The achievement of CMR at the completion of primary therapy identifies a group of patients with favourable outlook and a low risk of relapse. Surveillance PET-CT scanning within this select cohort has high sensitivity, specificity and NPV and despite the low number of relapses retains a high PPV, particularly in patients with IPI≥3. Surveillance PET-CT is useful in the first 18 months following completion of primary therapy in patients in whom IPI at diagnosis is ≥3. We feel that such a strategy would be appropriate to evaluate in a prospective comparative trial. Disclosures: No relevant conflicts of interest to declare.

Biweekly CHOP therapy improves therapeutic effect in the non-GCB subtype of diffuse large B-cell lymphoma

Open Medicine ◽  
2007 ◽  
Vol 2 (4) ◽  
pp. 488-498 ◽  
Author(s):  
Qingyuan Zhang ◽  
Jingxuan Wang ◽  
Jincai Wang
Keyword(s):  
B Cell ◽  
Standard Treatment ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Chop Regimen ◽  
Large B Cell Lymphoma ◽  
Germinal Center B Cell ◽  
Large B Cell ◽  
Chop Therapy

AbstractCHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) is accepted as the best available standard treatment for diffuse large B-cell lymphoma (DLBCL) patients; however, the therapeutic efficacy seems unsatisfactory. Additional rituximab will improve the cure rate, but it is not popular in China because of its increased medical cost. Germinal center B-cell (GCB) and non-GCB subtypes distinction have been described as independent prognostic factors, and provides likelihood for cure with chemotherapy. The aim of the study is to explore the association between Immunophenotype and treatment regimen. Between August 2003 and May 2006, 66 patients with DLBCL were enrolled, according to immunohistochemistry results (GCB and non-GCB phenotype), randomly assigned to receive either six to eight cycles of CHOP every 2 weeks or standard CHOP every 3 weeks. After a median follow-up duration of 32 months (range of 4 to 42 months), an estimated 3-year overall survival (OS) rate for the GCB patients were 68.2% and 55.6% for the biweekly CHOP regimen and standard CHOP regimen respectively, while the data were 62.8% and 37.9% respectively for the non-GCB cases. The biweekly CHOP therapy showed higher efficacy than standard treatment, and its superiority was more obvious with the non-GCB subgroup. All rights reserved.

scholarly journals C-MYC Protein Expression and High Ki-67 Proliferative Index are Predictives of Disease Relapse in Diffuse Large B Cell Lymphoma

2021 ◽  
Vol 6 (1) ◽  
pp. 15-20
Author(s):  
Mahmoud Tag El-Hussien ◽  
Nadia Mokhtar ◽  
Eman Naguib Khorshed
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Statistical Prediction ◽  
Proliferative Index ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Objective: To evaluate the status of C-MYC protein expression and Ki-67 proliferative index and to clarify their role in predicting relapse of diffuse large B cell lymphoma (DLBL). Materials and Methods: A retrospective study conducted on 50 cases diagnosed as DLBL in a 3 years’ time period from January 2014 till December 2016, collected from the archive of Pathology Departments of the National Cancer Institute Cairo - Egypt, Misr University for Science and Technology and private labs of authors. The diagnosis of DLBL for all cases, both nodal and extranodal, was confirmed by histopathologic examination and immunophenotyping. Automated immunohistochemical staining using antibodies against C-MYC protein and MIB-1 was used to evaluate the C-MYC expression in tumor cells and to assess their proliferative ability by calculating Ki-67 labelling index. The relation between the percentage of C-MYC protein expression, Ki-67 proliferative index, clinical data and the relapse status during the follow up period were analyzed. Results: A total of 50 cases of DLBL in both nodal and extra-nodal sites were included. Twenty-three cases (46%) were expressing the C-MYC protein, and 29 cases (58%) showed high Ki-67 proliferative index. Twenty-two cases (44%) relapsed during the follow-up period. Positive C-MYC protein expression was significantly associated with high Ki-67 proliferative index. C-MYC protein expression and high Ki-67 proliferative index were independently associated with disease relapses in 81.8% and 86.4% of cases respectively. Cases with combined C-MYC protein expression and high Ki-67 proliferative index showed statistical prediction of relapse in 81.8% of cases. Conclusion: C-MYC protein expression and high Ki-67 proliferative index were independently associated with relapse of diffuse large B cell lymphoma. Furthermore, the combined positive C-MYC protein expression and high Ki-67 proliferative index is better than a single positive test in predicting relapses among DLBL patients.

scholarly journals Single Centre Retrospective Analysis: Transformation of Waldenström's Macroglobulinemia to Diffuse Large B-Cell Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-11
Author(s):  
Bert Heyrman ◽  
Nikki Granacher ◽  
Ka Lung Wu
Keyword(s):  
B Cell ◽  
Retrospective Analysis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Single Centre ◽  
The Past ◽  
Large B Cell Lymphoma ◽  
End Of Treatment ◽  
Large B Cell

Introduction: The incidence and outcome of Waldenström's macroglobulinemia (WM) patients with transformation to diffuse large B-cell lymphoma (DLBCL) are unclear. We performed a retrospective analysis to determine the incidence, clinicopathological characteristics and treatment outcome of WM patient with histologic transformation to DLBCL in our centre. Methods: Single centre chart review of WM patients in the past 10 years. Patients with histologic diagnosis of DLBCL after the diagnosis WM were included in our analysis. Results: Three of the 79 WM patients had histological transformation to DLBCL, two male and one female. Mean age at DLBCL development was 76,6 years. The mean time to transformation since diagnosis of WM was 8,3 years (14, 8 and 3 years). All three patients received at least one prior line of treatment in relation to WM (2, 1 and 3 prior lines). Different regimens used were cyclophosphamide/dexamethasone, rituximab/bendamustin, chlorambucil monotherapy, fludarabine monotherapy, R-CVP and ibrutinib monotherapy. The patients were in clinical CR from WM at the time of transformation, two patients were still on treatment. All three patients presented with advanced disease (stage IIIB, IVB, and IVA) non-GCB subtype DLBCL with at least 2 extra nodal sites. R-IPI scores were 4,5 and 4. Two patients were treated with R-miniCHOP, one patient received R-CHOP. The first patient achieved a CR at the end of treatment and is now 1,5 years in follow-up. The second patient died from pneumonia one year after achieving a CR. The third patient is in follow op since 3 months after reaching a CR at the end of treatment. Conclusion: Over the past decade transformation of WM to DLBCL was 3.7% in our centre. This is in accordance with previous data suggesting an 2.4% risk of transformation over 10 years.Time to transformation varies and no association with prior WM therapy and response to treatment can be found.All patients presented with more aggressive DLBCL in an advanced stage.All three patients achieved a CR following treatment for DLBCL, one patient died from pneumonia, two others are now in follow-up 1,5 years and 3 months respectively. Disclosures Heyrman: Celgene:Research Funding.

scholarly journals Systematic Literature Review of the Clinical Evidence in Relapsed/Refractory (R/R) Large B-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5821-5821
Author(s):  
David G. Maloney ◽  
Fei Fei Liu ◽  
Lisette Nientker ◽  
Cathelijne Alleman ◽  
Brian Hutton ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Large B Cell

Introduction: Large B-cell lymphoma (LBCL) is the most common subtype of non-Hodgkin lymphoma. Frontline treatment is curative in ~60% of patients (pts); however, ~30% of pts relapse and ~10% are refractory to frontline treatment. Treatment options for pts with relapsed/refractory (R/R) disease, especially in the third-line or greater (3L+) setting, have been primarily salvage chemotherapies (CTs). Recently, 2 CAR T cell products, axicabtagene ciloleucel (Yescarta®) and tisagenlecleucel (Kymriah®), and the antibody-drug conjugate, polatuzumab vedotin (Polivy®), were approved in the 3L setting. A systematic literature review (SLR) of R/R LBCL was conducted to identify relevant evidence on clinical outcomes in LBCL pts, including these new therapies, within the second-line and greater (2L+) or 3L+ setting, and to define the unmet medical need. Methods: This SLR was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and European Union Health Technology Assessment requirements. The review identified randomized and nonrandomized/observational studies within R/R LBCL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma grade 3B (FL3B), primary mediastinal large B-cell lymphoma (PMBCL), DLBCL transformed from indolent lymphomas, and R/R DLBCL with secondary central nervous system (SCNS) involvement. Sources were EMBASE, MEDLINE, The Cochrane Library, and clinical conferences (ASCO, ESMO, EHA, ASH, ICML, AACR, and EORTC) from Jan 2000 to Apr 2019. Results : Following screening of 8683 database records and additional sources, 103 publications covering 78 unique studies were identified. Studies identified were characterized by line of treatment and R/R LBCL subtype (Figure). OS, PFS, DOR, OR, and safety observed from the identified studies were described. Disease subtypes, pt eligibility criteria, and length of follow-up varied notably across studies. In the 3L+ population, 11 salvage CT and 2 CAR T cell therapy studies reported survival outcomes. With salvage CT, the reported ORR across studies ranged from 0% to 54%, while CR ranged from 5.6%-31%. Median OS (mOS) ranged between 3-9 months, with one outlying study reporting mOS at 20 months. Median PFS (mPFS) reported within the salvage CT studies ranged from 2-6 months. Among CAR T cell therapies, pts treated with axicabtagene ciloleucel (n=101) reported a CR rate of 58% and median DOR (mDOR) was 11.1 months after a median follow-up of 27.1 months. mPFS was 5.9 months and mOS was not reached. At a median follow-up of 19.3 months, pts treated with tisagenlecleucel (n=115) had a CR of 40% but the mDOR was not reached. mOS was 11.1 months for all infused patients. In the 2L+ transplant-eligible population (36 studies), pts who received high-dose CT + HSCT achieved mOS between 9 months to 5 years. In the transplant noneligible population, 16 studies reported mOS between 3-20 months. Studies involving mixed transplant-eligible and noneligible populations (30 studies) reported mOS of 1-17 months. A few studies with limited sample sizes were found to report outcomes in LBCL subtypes (eg, PMBCL, SCNS lymphoma, DLBCL transformed from non-FL indolent lymphoma, FL3B). In the 3L+ setting, 1 study reported that mOS was not reached after a median of 6.6 months. In the 2L+ setting, 4 studies reported mPFS and mOS outcomes ranging between 2-9 months and 10-16 months, respectively. Among studies assessing safety of salvage CTs in R/R LBCL, neutropenia, leukocytopenia, thrombocytopenia, and infections were the most commonly reported adverse events (AEs), with neutropenia being the most reported. Among the 3 studies reporting safety outcomes of CAR T cell therapy, data suggest that hematologic AEs (possibly related to lymphodepleting CT), cytokine release syndrome, and neurotoxicity are the most reported. Conclusions : Despite the availability of new therapies for 2L+ and 3L + LBCL, examination of the current evidence has shown that there exists a high unmet need for additional therapeutic options that provide favorable benefit/risk and durable response for these patients. Furthermore, limited data are available for the rarer subtypes of LBCL. Both findings represent important treatment gaps for R/R LBCL that must be addressed in future research geared toward improvement of the current treatment landscape. Disclosures Maloney: Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; Celgene,Kite Pharma: Honoraria, Research Funding; BioLine RX, Gilead,Genentech,Novartis: Honoraria; A2 Biotherapeutics: Honoraria, Other: Stock options . Liu:Celgene Corporation: Employment. Nientker:Celgene Corporation: Consultancy; Pharmerit Cöoperatief U.A.: Employment. Alleman:Pharmerit Cöoperatief U.A.: Employment; Celgene Corporation: Consultancy. Garcia:Celgene: Employment, Equity Ownership.

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