Pleural effusion at diagnosis predicts extremely poor outcomes in patients with diffuse large B‐cell lymphoma harbouring MYC rearrangement

2018 ◽  
Vol 185 (1) ◽  
pp. 183-187 ◽  
Author(s):  
Hideaki Nitta ◽  
Akihiko Gotoh ◽  
Masaru Tanaka ◽  
Yasunobu Sekiguchi ◽  
Yasunori Ota ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Poor Outcomes ◽  
Large B Cell

scholarly journals UCH-L1 is induced in germinal center B cells and identifies patients with aggressive germinal center diffuse large B-cell lymphoma

Blood ◽  
2016 ◽  
Vol 127 (12) ◽  
pp. 1564-1574 ◽  
Author(s):  
Tibor Bedekovics ◽  
Sajjad Hussain ◽  
Andrew L. Feldman ◽  
Paul J. Galardy
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Neuronal Marker ◽  
Large B Cell Lymphoma ◽  
Increased Risk ◽  
Key Points ◽  
Poor Outcomes ◽  
Large B Cell

Key Points The neuronal marker UCH-L1 is induced in, and specifically augments the oncogene-induced transformation of, GCB cells. High levels of UCHL1 identify patients with GC DLBCL with an increased risk for poor outcomes.

scholarly journals Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study

Blood ◽  
2017 ◽  
Vol 130 (16) ◽  
pp. 1800-1808 ◽  
Author(s):  
Michael Crump ◽  
Sattva S. Neelapu ◽  
Umar Farooq ◽  
Eric Van Den Neste ◽  
John Kuruvilla ◽  
...  
Keyword(s):  
B Cell ◽  
Randomized Trials ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Patient Level ◽  
Large B Cell Lymphoma ◽  
Key Points ◽  
Poor Outcomes ◽  
Level Analysis ◽  
Large B Cell

Key Points SCHOLAR-1 is the first patient-level analysis of outcomes of refractory DLBCL from 2 large randomized trials and 2 academic databases. SCHOLAR-1 demonstrated poor outcomes in patients with refractory DLBCL, supporting a need for more effective therapies for these patients.

scholarly journals A case of diffuse large B‐cell lymphoma originating from chest wall complicated by benign asbestos pleural effusion

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Nobuyuki Kondo ◽  
Yukihisa Inoue ◽  
Hiroaki Takeyama ◽  
Akiko Kobayashi ◽  
Osamu Matsubara ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
B Cell ◽  
Chest Wall ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

scholarly journals A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma

2017 ◽  
Vol 10 (3) ◽  
pp. 1013-1022 ◽  
Author(s):  
Daisuke Usuda ◽  
Masahisa Arahata ◽  
Kento Takeshima ◽  
Ryusho Sangen ◽  
Akiteru Takamura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pleural Effusion ◽  
B Cell ◽  
Hematological Malignancy ◽  
Cell Lymphoma ◽  
Primary Effusion Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Disturbance Of Consciousness ◽  
Large B Cell

A 93-year-old female was transferred to the emergency ward of our hospital due to disturbance of consciousness and hypotension. Computed tomography showed bilateral pleural and pericardial effusion without evidence of tumor masses or lymphadenopathy. Cytodiagnosis of pleural effusion revealed proliferation of atypical lymphoid-like cells with pan-B surface markers. We suspected primary effusion lymphoma-like lymphoma; however, the monoclonality of these cells was not confirmed. Cytodiagnosis of bone marrow revealed lymphoma cells with monoclonal B-cell markers. These findings prompted a diagnosis of diffuse large B-cell lymphoma with bone marrow invasion. In the case of pericardial or pleural effusion, clinicians should consider carefully both hematological malignancy and its classification.

scholarly journals Tumor ADAM10/ADAM17-Mediated PD-L1 Loss May Predict Poor Outcomes in Diffuse Large B Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4120-4120 ◽  
Author(s):  
Jacob Orme ◽  
Jose Villasboas ◽  
Haidong Dong
Keyword(s):  
B Cell ◽  
Cell Line ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoma Cell ◽  
Lymphoma Cell Line ◽  
Large B Cell Lymphoma ◽  
Poor Outcomes ◽  
L1 Protein ◽  
Large B Cell

Introduction Tumor surface matrix metalloproteases ADAM10 and ADAM17 are associated with poor outcomes in multiple malignancies. We previously showed that these proteases shed PD-L1 from lymphoma cell line Karpas-299 to produce soluble PD-L1 (sPD-L1) that induces CD8+ T cell apoptosis (1). While higher levels of soluble PD-L1 are associated with worse prognosis in patients with non-Hodgkin lymphoma treated with standard chemoimmunotherapy (cutoff of 1.52 ng/ml, 3-year OS of 76% versus 89%) (2), it is unknown whether the loss of PD-L1 on the surface of B cell lymphoma cells affects clinical outcomes. We hypothesized that tumors expressing low PD-L1 levels despite high PD-L1 mRNA levels would (1) produce higher ADAM10 or ADAM17 transcript levels and (2) predict poorer prognosis in diffuse large B cell lymphomas. Methods We queried the cancer genome atlas (TCGA) public database for cases of diffuse large B cell lymphoma (DLBCL) for which PD-L1 (CD274) protein levels are reported by reverse phase protein array (RPPA). We then queried TCGA for RNA-Seq data for CD274, ADAM10, and ADAM17 expressed as transcripts per million (FPKM). We re-normalized RPPA data and calculated a PD-L1 protein-to-mRNA ratio for each tumor sample. We then compared groups of high and low PD-L1 protein-to-mRNA ratios for ADAM10 and ADAM17 mRNA expression. We further compared groups of high and low PD-L1 protein-to-mRNA ratios for survival (adjusted for age at diagnosis). All statistical analyses were performed using R Statistical Software (R Foundation). Unpaired student's t-test assessed statistical differences in experimental groups except where otherwise indicated. Figures comprise box plots showing quartile values and individual data points. P<0.05 was considered statistically significant. In figures, p values are denoted <0.05 with *, <0.01 with **, and <0.001 with ***. Results Data were available for a total of 33 diffuse large B cell (DLBC) lymphomas. 18 of those samples were categorized as having low PD-L1 protein-to-mRNA ratios (cutoff 6.38e-6) with the remaining categorized as high ratio. DLBCL tumors demonstrating low PD-L1 protein-to-mRNA ratios expressed significantly higher ADAM10 (p=0.0237) and ADAM17 (p<0.0001) transcripts than tumors expressing low PD-L1 protein-to-mRNA ratios (Figure 1). Furthermore, patients with tumors demonstrating low PD-L1 protein-to-mRNA ratios experienced significantly poorer survival according to likelihood ratio (6.6, p=0.01) and log rank (4.67, p=0.03) tests (Figure 2). Conclusions Our findings may explain a crucial phenomenon seen in diffuse large B cell lymphoma, namely that many purportedly PD-L1-positive tumors appear to express PD-L1 but do not respond to PD-(L)1 inhibitor therapy (3,4). This may be caused by the activity of ADAM10 and ADAM17 to cleave PD-L1, which we previously showed in lymphoma cell line Karpas-299 (1). This posits pre-treatment ADAM10/ADAM17 inhibition to "boost" PD-(L)1 inhibitor therapy in lymphoma. Our results contrast with previous findings that PD-L1-positive DLBCL progression free survival is inferior to PD-L1-negative DLBCL (5). This may be due to different methods of protein detection (immunohistochemistry versus RPPA) and the lack of localization of PD-L1 expression in tumor cells versus the microenvironment. Notably, this study is only correlative with a limited case number. Larger prospective studies will be needed to further elucidate this relationship. Acknowledgments The results shown here are in whole or part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. References 1. Orme et al. AACR Adv Malig Lymphoma 2018. Pres 423 2. Rossille et al. Leukemia 2014. 28:2367-75. 3. Moskowitz et al. Blood 2014 124:290. 4. Armand et al. J Clin Oncol 2013. 31:4199-206. 5. Kiyasu et al. 2015.126:2193-201. Figure Disclosures No relevant conflicts of interest to declare.

Outcomes in large B-cell lymphoma progressing after axicabtagene ciloleucel (Axi-cel): Results from the U.S. Lymphoma CAR-T Consortium.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7517-7517 ◽  
Author(s):  
Jay Y. Spiegel ◽  
Saurabh Dahiya ◽  
Michael D. Jain ◽  
Loretta J. Nastoupil ◽  
Armin Ghobadi ◽  
...  
Keyword(s):  
B Cell ◽  
Salvage Therapy ◽  
Cell Lymphoma ◽  
Checkpoint Inhibitors ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Response Status ◽  
Poor Outcomes ◽  
Large B Cell

7517 Background: Axi-cel, an anti-CD19 CART cell therapy, achieved 83% ORR, 58% CR rate, with 39% PFS at 2 years in patients (pts) with relapsed refractory large B-cell lymphoma (LBCL) on the ZUMA-1 study (Locke, Lancet Oncology 2018). Data from a 17-center consortium showed response rates were similar in 274 pts treated with commercial axi-cel (Nastoupil, ASH 2018). Here, we performed retrospective analysis of outcomes in pts with progressive disease (PD) after axi-cel. Methods: Response status was determined by Cheson 2014 and reported as date of radiologic relapse. 274 pts were infused by December 26, 2018 with maximum follow-up of 14 months; 116 pts had PD as of Feb 1, 2019. Twelve sites provided additional data, detailing 85% of PD pts (n=99) with a median time to relapse of 54 days (IQR 16-120). Results: Pre axi-cel pt characteristics: median lines of therapy were 4 (range 2-11), 86% were Stage III/IV and 22% were ECOG >1. Following relapse, 60% (n=61) were biopsied and 70% (43/61) had CD19 expression measured. Thirty percent (13/43) were CD19 negative by: IHC (3/13), flow (2/13) or both (8/13). Seventy percent (n=71) received salvage therapy for PD. Median lines of salvage therapy was 1 (range 0-4). The most common therapies were Lenalidomide-based (30%), checkpoint inhibitors (30%), chemotherapy (20%) and radiation (10%). First salvage therapy ORR by regimen: checkpoint inhibitors = 24%, lenalidomide regimens = 20% and chemotherapy = 11%. One patient received allogeneic transplant. Twelve pts enrolled on clinical trial, with one receiving 2nd CAR-T. Median OS following relapse was 108 days (95% LCL 71). Nineteen pts relapsed <3 months after axi-cel and did not receive therapy with median OS 17 days (95% CI 7-49); 33 pts relapsed <3 months and received therapy with 114 day median OS (95% LCL 82). In contrast, 30 pts who relapsed >3 months post axi-cel and received therapy had estimated median OS >220 days (95% LCL 81). Conclusions: Patients with LBCL relapsing less than 3 months following axi-cel have extremely poor outcomes supporting the development of novel therapies. Therapy for relapse >3 months appears promising. JYS and SD contributed equally; APR, DBM and BTH contributed equally.

scholarly journals Patient Case Studies and Panel Discussion: Lymphoma

2019 ◽  
Vol 17 (11.5) ◽  
pp. 1420-1423
Keyword(s):  
B Cell ◽  
Case Studies ◽  
Cell Lymphoma ◽  
Panel Discussion ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
Peripheral T Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Poor Outcomes ◽  
Large B Cell

A heterogeneous group of diseases, lymphomas encompass a range of diagnoses that call for varied treatment approaches. Although some lymphomas require minimal intervention for cure or remission, others can be very difficult to treat and are associated with poor outcomes. At the NCCN 2019 Annual Congress: Hematologic Malignancies, a panel of experts used 3 case studies to develop an evidence-based approach for the treatment of patients with lymphomas. Moderated by Ranjana H. Advani, MD, the session focused on peripheral T-cell lymphoma, primary mediastinal large B-cell lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma.

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