B-cell Lymphoma 2 rs17757541 C>G Polymorphism was Associated with an Increased Risk of Gastric Cardiac Adenocarcinoma in a Chinese Population

Abstract The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6. These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium.

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

Blood ◽

10.1182/blood-2015-07-656678 ◽

2016 ◽

Vol 127 (12) ◽

pp. 1564-1574 ◽

Cited By ~ 21

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.

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Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211623 ◽

2017 ◽

Vol 76 (12) ◽

pp. 2025-2030 ◽

Cited By ~ 32

Author(s):

Louise K Mercer ◽

Anne C Regierer ◽

Xavier Mariette ◽

William G Dixon ◽

Eva Baecklund ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

General Population ◽

B Cell ◽

Hodgkin’S Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Hodgkin's Lymphoma ◽

Treatment Groups ◽

Increased Risk

BackgroundLymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes.MethodsPatients never exposed to (bionaïve) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD.ResultsAmong 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaïve patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population.ConclusionThis large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaïve patients.

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Increased risk of venous thromboembolism in patients with primary mediastinal large B-cell lymphoma

Thrombosis Research ◽

10.1016/j.thromres.2010.08.017 ◽

2010 ◽

Vol 126 (6) ◽

pp. 477-480 ◽

Cited By ~ 19

Author(s):

Danijela Lekovic ◽

Predrag Miljic ◽

Biljana Mihaljevic

Keyword(s):

Venous Thromboembolism ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Increased Risk ◽

Large B Cell

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Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma

Blood ◽

10.1182/blood-2010-07-295097 ◽

2011 ◽

Vol 117 (2) ◽

pp. 585-590 ◽

Cited By ~ 26

Author(s):

Yingtai Chen ◽

Tongzhang Zheng ◽

Qing Lan ◽

Francine Foss ◽

Christopher Kim ◽

...

Keyword(s):

Body Mass Index ◽

B Cell ◽

Hodgkin Lymphoma ◽

Body Mass ◽

Significant Interaction ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Lymphocytic Leukemia ◽

Non Hodgkin Lymphoma ◽

Increased Risk

Abstract We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m2, women with BMI more than or equal to 25 kg/m2 had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 Pforinteraction = .034) and IL7R (rs1494555 Pforinteraction = .016) for NHL overall; IL7R (rs1494555 Pforinteraction = .016) and TNF (1799724 Pforinteraction = .031) for B-cell lymphoma; and IL5 (rs2069812 Pforinteraction = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 Pforinteraction = .006), IL13 (rs20541 Pforinteraction = .019), and IL7R (rs1494555 Pforinteraction = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 Pforinteraction = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 Pforinteraction = .013) and TNF (1799724 Pforinteraction = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.

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Primary Mediastinal Large B-Cell Lymphoma With Sclerosis in Pediatric and Adolescent Patients: Treatment and Results From Three Therapeutic Studies of the Berlin-Frankfurt-Münster Group

Journal of Clinical Oncology ◽

10.1200/jco.2003.08.151 ◽

2003 ◽

Vol 21 (9) ◽

pp. 1782-1789 ◽

Cited By ~ 62

Author(s):

K. Seidemann ◽

M. Tiemann ◽

I. Lauterbach ◽

G. Mann ◽

I. Simonitsch ◽

...

Keyword(s):

Cell Therapy ◽

B Cell ◽

Pediatric Patients ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Serum Lactate Dehydrogenase ◽

High Dose ◽

Large B Cell Lymphoma ◽

Increased Risk ◽

Large B Cell

Purpose: Primary mediastinal large B-cell lymphoma with sclerosis (PMLBL) is a rare entity of non-Hodgkin’s lymphoma (NHL) arising from thymic mature B cells. Optimal treatment strategies remain to be established, especially in pediatric patients. Patients and Methods: This study analyzes clinical characteristics and treatment outcome of 30 pediatric patients with PMLBL, diagnosed in multicenter therapy NHL–Berlin-Frankfurt-Münster Group (BFM) trials. Treatment was stratified by stage and serum lactate dehydrogenase (LDH) and consisted of four to six 5-day courses of chemotherapy using steroids, oxazaphosphorine alkylating agents, methotrexate, cytarabine, etoposide, and doxorubicin. Radiation was not part of the protocol. Results: From April 1986 to August 1999, 1,650 patients with newly diagnosed NHL were enrolled in the NHL-BFM trials; 30 patients (1.8%) had PMLBL. Median age was 14.3 years (range, 1.4 to 16.7 years); 15 patients were male and 15 patients were female. With a median observation time of 5 years (range, 1 to 12 years), probability of event-free survival (pEFS) at 5 years was 0.70 (SE, 0.08). Two patients erroneously diagnosed as T-cell NHL received non–B-cell therapy and died from progress of disease. Events in 28 patients receiving B-cell therapy included early progress during therapy (n = 1) and relapse (n = 6). Residual mediastinal masses were present in 23 patients after two courses of therapy and in 15 patients after the end of therapy. LDH ≥ 500 U/L was associated with increased risk of failure in multivariate analysis. Conclusion: PMLBL mainly is found in adolescents. Dose-intense chemotherapy including high-dose methotrexate yields a pEFS at 5 years of 0.70 (SE, 0.08). LDH is of prognostic value in pediatric patients with PMLBL.

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B-cell lymphoma of the larynx in a patient with rheumatoid arthritis

The Journal of Laryngology & Otology ◽

10.1258/0022215054516179 ◽

2005 ◽

Vol 119 (8) ◽

pp. 646-648 ◽

Cited By ~ 9

Author(s):

S Patiar ◽

J D Ramsden ◽

A P Freeland

Keyword(s):

Rheumatoid Arthritis ◽

Rheumatoid Arthritis Patient ◽

B Cell ◽

Cell Lymphoma ◽

Treatment Options ◽

B Cell Lymphoma ◽

Primary Site ◽

Hodgkin's Lymphoma ◽

Increased Risk ◽

Previously Treated

We report a case of B-cell lymphoma with the larynx as the primary site of presentation in a rheumatoid arthritis patient previously treated with methotrexate. Primary non-Hodgkin’s lymphoma (NHL) of the larynx is rare. There may be an increased risk of lymphoma in patients with rheumatoid arthritis, with an even higher risk in those patients treated with methotrexate. The diagnostic and treatment options are discussed.

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Clinical significance and detection of microRNA-21 in serum of patients with diffuse large B-cell lymphoma in Chinese population

European Journal Of Haematology ◽

10.1111/ejh.12263 ◽

2014 ◽

Vol 92 (5) ◽

pp. 407-412 ◽

Cited By ~ 38

Author(s):

Weiqun Chen ◽

Hui Wang ◽

Heming Chen ◽

Shuiyi Liu ◽

Hongda Lu ◽

...

Keyword(s):

B Cell ◽

Clinical Significance ◽

Chinese Population ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

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Risk of lymphoma subtypes by occupational exposure in Southern Italy

Journal of Occupational Medicine and Toxicology ◽

10.1186/s12995-017-0177-2 ◽

2017 ◽

Vol 12 (1) ◽

Cited By ~ 6

Author(s):

Giovanni Maria Ferri ◽

Giorgina Specchia ◽

Patrizio Mazza ◽

Giuseppe Ingravallo ◽

Graziana Intranuovo ◽

...

Keyword(s):

Occupational Exposure ◽

B Cell ◽

Southern Italy ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Agricultural Activity ◽

Retrospective Assessment ◽

Non Hodgkin Lymphoma ◽

Complete Work ◽

Increased Risk

Abstract Background Occupational exposure is known to play a role in the aetiology of lymphomas. The aim of the present work was to explore the occupational risk of the major B-cell lymphoma subtypes using a case–control study design. Methods From 2009 to 2014, we recruited 158 lymphoma cases and 76 controls in the provinces of Bari and Taranto (Apulia, Southern Italy). A retrospective assessment of occupational exposure based on complete work histories and the Carcinogen Exposure (CAREX) job-exposure matrix was performed. Results After adjusting for major confounding factors, farmers showed an increased risk of diffuse large B-cell lymphoma (DLBCL) [odds ratio (OR) = 10.9 (2.3–51.6)] and multiple myeloma (MM) [OR = 16.5 (1.4–195.7)]; exposure to the fungicide Captafol was significantly associated with risk of non-Hodgkin lymphoma (NHL) [OR = 2.6 (1.1–8.2)], particularly with the risk of DLBCL [OR = 5.3 (1.6–17.3)]. Conclusions Agricultural activity seems to be a risk factor for developing lymphoma subtypes, particularly DLBCL, in the provinces of Bari and Taranto (Apulia Region, Southern Italy). Exposure to the pesticides Captafol, Paraquat and Radon might be implicated. Trial registration Protocol number UNIBA 2207WEJLZB_004 registered 22/09/2008.

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Adding Etoposide to R-CHOP (R-CHOEP) Does Not Significantly Increase the Risk of Secondary Neoplasms in Patients with Aggressive B-Cell Lymphoma - Results from Randomized Phase 3 Trials of the German Lymphoma Alliance (GLA)

Blood ◽

10.1182/blood-2020-138412 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 5-6

Author(s):

Fabian Frontzek ◽

Marita Ziepert ◽

Maike Nickelsen ◽

Bettina Altmann ◽

Bertram Glass ◽

...

Keyword(s):

B Cell ◽

Solid Tumors ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Advisory Board ◽

First Line ◽

Phase 3 ◽

Increased Risk ◽

Aggressive B Cell Lymphoma

Introduction:Considering the increasing numbers of lymphoma patients (pts) surviving long-term, late effects of current treatment strategies such as secondary (sec) malignancies gain increasing importance. Many treatment regimens used in pts with lymphoma (R-CHOEP, DA-EPOCH-R, BEACOPP) include etoposide, a cytotoxic agent reported to increase sec leukemias. In order to further investigate the role of etoposide in inducing sec malignancies in pts with aggressive lymphoma we analyzed the R-MegaCHOEP trial (Schmitz et al., Lancet Oncology 2012) where young, high-risk pts with aggressive B-cell lymphomas had received R-CHOEP or R-MegaCHOEP, a regimen containing very high doses of etoposide (4g/m2). We compared rates of secondary tumors to incidences found in young patients treated with R-CHOP only. Methods:We analyzed 1536 pts aged 18-60 years with aggressive B-cell lymphoma treated in the prospective phase 3 trials FLYER (NCT00278421; n=588, median observation time (OT)=66 months), UNFOLDER (NCT00278408; n=695, median OT=72 months) and MegaCHOEP (NCT00129090; n=253, median OT=112 months) to compare the cumulative incidences of sec neoplasms. We performed a competing risk analysis for time from randomization to occurrence of sec malignancy (myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or other) according to first-line therapy with R-CHOP (n=1283) vs. R-CHOEP (n=127) vs. R-MegaCHOEP (n=126). We used a cause-specific hazard model adjusted for gender, age (>50 vs. <= 50 years) and radiotherapy. Results:Adjusting for competing events, we found sec MDS/AML in 0.3% of pts treated with R-CHOP, in 1% of pts treated with R-CHOEP and in 2% of pts following treatment with R-MegaCHOEP. Cause-specific hazard ratios showed a trend for increased risk for sec AML following R-MegaCHOEP in comparison to R-CHOP (HR 5.2, 95%CI (1.0; 27.5), p=0.052) while R-CHOEP did not significantly increase the incidence of sec AML (HR 1.4, 95%CI (0.1; 14.0), p=0.777). Male gender and age >50 years showed a trend for increasing sec AML. We found very similar incidences of sec solid tumors (not MDS/AML) affecting 4% of pts treated with R-CHOP or R-MegaCHOEP and 6% of pts following R-CHOEP regimen. The only factor significantly increasing the risk of sec solid tumors was age >50 years (HR 2.6, 95%CI (1.5; 4.3), p<0.001). Conclusions:This analysis shows that sec malignancies represent rare events in younger patients with aggressive B-cell lymphoma, even after extreme dose-escalation of etoposide. Compared to standard R-CHOP, 8 cycles of R-CHOEP were not associated with increased risk of sec AML or solid tumors thus remaining an attractive first-line treatment for young high-risk pts with DLBCL. Disclosures Haenel: Amgen, Novartis, Roche, Celgene, Takeda, Bayer:Honoraria.Truemper:Janssen:Consultancy;Mundipharma:Research Funding;Nordic Nanovector:Consultancy;Roche:Research Funding;Seattle Genetics:Research Funding;Takeda Europe:Consultancy, Research Funding.Held:MSD:Consultancy;Acrotech, Spectrum:Research Funding;Amgen:Research Funding;BMS:Consultancy, Other: Travel Grants, Research Funding;Roche:Consultancy, Other: travel grants, Research Funding.Borchmann:Bristol Myers Squibb:Research Funding;Takeda:Research Funding.Dreyling:Celgene:Consultancy, Research Funding, Speakers Bureau;Roche:Consultancy, Research Funding, Speakers Bureau;Beigene:Consultancy;Janssen:Consultancy, Research Funding, Speakers Bureau;Novartis:Consultancy;Abbvie:Research Funding;Astra Zeneca:Consultancy;Bayer:Consultancy, Speakers Bureau;Gilead:Consultancy, Research Funding, Speakers Bureau.Viardot:Roche:Honoraria, Other: advisory board;Kite/Gilead:Honoraria, Other: advisory board;Novartis:Honoraria, Other: advisory board;Amgen:Honoraria, Other: advisory board.Kroschinsky:Riemsser:Research Funding;Roche:Consultancy, Honoraria, Other: Support of parent study and funding of editorial support;Gilead:Consultancy;BMS/Celgene:Consultancy, Honoraria;Sandoz:Research Funding.Ott:NIH:Consultancy, Other: Co-inventor on a patent related to the MCL35 assay filed at the National Institutes of Health, United States of America..Lenz:Bayer:Consultancy, Honoraria, Research Funding, Speakers Bureau;Janssen:Consultancy, Honoraria, Research Funding, Speakers Bureau;Novartis:Consultancy;Gilead:Consultancy, Honoraria, Research Funding, Speakers Bureau;AQUINOX:Research Funding;AstraZeneca:Consultancy, Honoraria, Research Funding;Celgene:Consultancy, Honoraria, Speakers Bureau;Verastem:Research Funding;Morphosys:Consultancy, Honoraria, Research Funding;Roche:Consultancy, Honoraria, Research Funding, Speakers Bureau;Agios:Research Funding;BMS:Consultancy.Schmitz:Riemser:Honoraria;Takeda:Honoraria;Janssen:Research Funding;Bristol-Myers Squibb:Current equity holder in publicly-traded company.

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