Search

Objectives: Direct-acting antiviral agents (DAAs) have successfully eradicated chronic hepatitis C virus (HCV) infection. Since chronic HCV is known to have an increased risk of developing B cell non-Hodgkin lymphoma (B-NHL), successful HCV treatment may have virologic, hepatic, and oncologic benefits for B-NHL. Therefore, this study aimed to determine the efficacy of DAAs combined with chemotherapy in B-NHL patients with chronic HCV in Mongolia. Methods: This case-control study included newly diagnosed B-NHL patients with chronic HCV who received DAAs before chemotherapy (with DAAs group). The other is comprised of controls who have been treated by chemotherapy without DAAs. Patients who received courses of DAAs were monitored by the virological and hepatic responses. Results: Eleven patients received DAAs and none of them developed chemotherapy-associated hepatitis flare. Of the DAAs group, during DAAs treatment, 90.9% were clinically stable. In all cases of DAAs in combination with chemotherapy, the Sustained Viral Response (SVR)12 and 24 were 100%. However, 47.4% of those who received DAAs after chemotherapy developed hepatitis flare during chemotherapy. Patients with hepatitis flare had higher serum level of ALT before chemotherapy (15.7 U/L vs. 40.2 U/L; p = 0.014) than those without. Conclusion: DAAs administration results in a significant clinical benefit to B-NHL patients with chronic HCV.

Low-grade B cell non-Hodgkin's lymphoma with dominant presentation of chest wall mass is presented in this report. The patient, a 65-year-old woman, presented with pain, rising skin temperature and redness, and swelling on the right lower chest wall. The histopathological examination revealed non-Hodgkin's lymphoma; the staging fluorodeoxyglucose-positron emission tomography/computed tomography demonstrated stage IVE disease, with hypermetabolic active disease in the right anterolateral chest wall in the form of large soft tissue mass and subcutaneous tissue with underlying bony erosion with extension into right anterior cardiophrenic space and superiorly up to right second costosternal region along the right internal mammary vessels. This was along with hypermetabolic active right axillary, right supraclavicular and left inguinal lymphadenopathy, and thickened hypermetabolic posterior right pleura with ametabolic right-sided pleural effusion. Bone marrow biopsy revealed uninvolved bone marrow. On follow-up after eight cycles of R-CHOP chemotherapy, the mass had completely resolved on contrast-enhanced computed tomography. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Chronic Hepatitis C virus (HCV) infection can cause severe extrahepatic manifestations, such as mixed cryoglobulins (MC), up to the development of B cell nonHodgkin’s lymphoma (B-NHL). Mechanisms transforming of HCV infection into lymphoproliferative and/or autoimmune disorders are still poorly understood. In course of HCV infection, the sustained virus-driven antigenic stimulation may probably induce a B-cell clonal expansion. Measurements of serum free light chains (FLCs) levels, considered as a direct marker of B cell activity, are analyzed with increasing interest in clinical practice, for diagnosis, monitoring and follow-up of plasma cell dyscrasia. Syndecan-1 (CD138) is a transmembrane heparan sulfate proteoglycan expressed and actively shed by most myeloma cells. Membrane CD138 represents the major receptor protein for HCV attachment to the hepatocyte surface and high levels of circulating sCD138 levels are detected in patients at early stage of B-cell chronic lymphocytic leukemia. This study is aimed to evaluate sCD138 and FLC levels as diagnostic biomarkers of HCV-related MC with B-NHL. PATIENTS AND METHODS: We enrolled 35 HCV-MC-NHL patients, characterized for the specific type of cryoglobulins, and 25 healthy blood donors (HBD) as negative control. Serum sCD138 levels were determined using ELISA kits specific for human sCD138. Serum FLCs were assessed by means of the turbidimetric assay. RESULTS: We found that serum levels of sCD138, as well as FLCs, were significantly higher in patients than in HBD (p<0.001). CONCLUSIONS: In agreement with the definition of HCV-driven lymphoproliferative disorders as the consequence of a multifactorial and multistep pathogenetic process, we suggest that sCD138 and FLCs could be considered putative independent markers of worsening progression of the disease. [ABSTRACT FROM AUTHOR]

Neoplastic transformation of germinal center B (GCB) cells may give rise to a variety of different B cell lymphoma subtypes, most of which show substantial heterogeneity in terms of genetic alterations and clinical features. The mutations observed in cancerrelated genes in GCB cells are related to abnormalities in the immunogenetic mechanisms associated with germinal center reaction. Recent studies have rapidly identified genomic alterations in B cell lymphomas that may be useful for better subclassification, noninvasive diagnosis, and prediction of response to therapy. The WHO recognizes different lymphoma subsets classified within 2 major categories of B cell lymphoma: Hodgkin's lymphoma (HL) and B cell non-Hodgkin's lymphoma (NHL), each with distinct genetic aberrations, including chromosomal translocations, copy number abnormalities, or point mutations. Next-generation sequencing-based technologies have allowed cancer researchers to identify somatic mutations and gene expression signatures at a rapid pace so that novel diagnostic or prognostic biomarkers, as well as therapeutic targets, can be discovered much faster than before. Indeed, deep sequencing studies have recently revealed that lymphoma-specific somatic mutations may be detected in cell-free circulating DNA obtained from the peripheral blood of B cell lymphoma patients, suggesting the possibility of minimally invasive diagnosis, monitoring, and predicting response to therapy of B cell lymphoma patients. In this study, the current status of the recurrent genetic aberrations observed during diagnosis and/ or relapse in HL and the major subtypes of B cell NHL (i.e. diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, and Burkitt lymphoma) are discussed to shed light on their potential use as noninvasive diagnostic or prognostic biomarkers and to reveal their role in lymphomagenesis as a target in therapy for newly diagnosed and chemotherapy-resistant cases. [ABSTRACT FROM AUTHOR]

B and T lymphocyte attenuator (BTLA) is a lymphocyte inhibitory receptor mainly expressed on several subsets of T and B lymphocytes. In the current retrospective study, BTLA expression is examined for the first time on formalin fixed and paraffin embedded (FFPE) tissue sections of mature B cell non-Hodgkin's lymphomas (253 cases), using a newly developed monoclonal antibody. BTLA is highly expressed in chronic lymphocytic leukemia/small lymphocytic lymphoma. In contrast, BTLA expression is nearly absent in mantle cell lymphoma and is not expressed in any of the follicular lymphoma cases of all grades. In marginal zone lymphoma, diffuse large B cell lymphoma, and Burkitt's lymphoma, a minority of the cases exhibit expression of BTLA. This study demonstrates the value of BTLA expression as an additional tool in the panel of immunochemical markers used for the differential diagnosis of mature B cell lymphomas in FFPE tissue sections. [ABSTRACT FROM AUTHOR]

To exploit the B-lymphocyte antigen-CD20 binding capa­city of the Ibritumomab tiuxetan (IBTN) monoclonal antibody (mAb) for imaging, the over-expression of B cells in non-Hodgkin's lymphoma (NHL) (a myeloproliferative disorder of the lymphatic system) was investigated. In the current investigation, we present the labeling of the IBTN with technetium-99m (99mTc) through [99mTc(CO)3]+ precursor for radioimmunoimaging (RII) of the tumor prior to its treatment with 90Y labeled IBTN. Labeled IBTN was radiobiologically characterized in terms of radiochemical purity, in vitro stability in human plasma, immunoreactivity, binding with Raji and Ramos cells and biodistribution in a female nude mouse (FNM) model. It was observed that the reduced IBTN (rIBTN) showed more promising radiobiologic characteristics than the nonreduced IBTN. Significantly higher transchelation was seen in excess cysteine compared with histidine. The radioconjugate showed higher saturated binding affinity with CD20 antigen. Significantly higher target (tumor) to background ratios were observed 1 h post-injection (p.i.). Based on radiochemical purity, in vitro stability, immunoreactivity, binding and biodistrubtion in the FNM model, we recommend the radiolabeling of the rIBTN using tricarbonyl technique as a potential RII agent. [ABSTRACT FROM AUTHOR]

OBJECTIVES: B-cell Non-Hodgkin's lymphoma (B-NHL) is one of the increasing cancer species over the world. DICER1 gene is a member of ribonuclease type III family and it plays a crucial role in biogenesis of miRNAs that regulates the gene expression in posttranscriptional level. In addition, studies have showed that the germline mutations in DICER1 exon 11 may be hazardous because they result in frame shift and exon 25 mutations play role in biogenesis of miRNA. BAFF is expressed by immune system cells such as monocytes, macrophages, dendritic cells, a subtype of T-lymphocytes and B-lymphocytes. Studies, that has been done till now, show high levels BAFF gene expression in malignant B-cells of patients with B-NHL. MATERIAL&METHODS: In our study, DICER1 c.+3473A>G (rs3742330) and BAFF c.-871C>T (rs9514828) single nucleotide polymorphisms in DNA materials, that were isolated from peripheral blood samples of 60 patients that were diagnosed B-cell non-Hodgkin's lymphoma and 30 healthy people matched with patients by age, sex and ethnicity, were examined with PCR-RFLP method. RESULTS: The detection of mutation existence in exon11 and 25 in DICER1 gene was examined by SANGER sequencing analysis. Chi-Square and Fisher tests were used for evaluation of the results between control and patient groups. No significant results were found between the two groups (p > 0, 05). CONCLUSIONS: In our study, the presence of mutations and polymorphisms related to DICER1 and BAFF genes was not found in patients with B cell non- Hodgkin lymphoma. It is thought that the disease may be related to other factors in the patient group in our study. [ABSTRACT FROM AUTHOR]

Introduction : Blinatumomab, a first-in-class bispecific T cell engager, is a member of a novel class of bispecific antibody constructs with dual binding specificities. While its primary clinical use has been in B cell acute lymphoblastic leukemia, its role in the treatment of B cell non-Hodgkin's Lymphoma (NHL) is less well established. Areas covered : Herein, the authors provide a brief overview of the market, unmet needs, and how blinatumomab fits in to the evolving armamentarium of lymphoma-directed therapies. The authors address its therapeutic role in salvage therapy for relapsed/refractory NHL, as consolidation for high-risk diffuse large B cell lymphoma (DLBCL) following ASCT, and through various combinations with other available agents. Moreover, authors highlight key competitors. Expert opinion : Although blinatumomab showed impressive results in phase I and II studies for relapsed/refractory DLBCL, its future utility remains to be seen in this clinical setting due to lack of phase III trial and FDA approval of CD19 CART therapy. A new CD19/CD3 and several CD20/CD3 bispecific antibodies with longer half-life and resultant easier mode of administration which can overcome the major barriers of its use in clinical practice are in the pipeline and their role in NHL treatment are actively explored.

CD19-targeted chimeric antigen receptor-T (CAR-T) cells with CD28 or 4-1BB (28z CAR-T and BBz CAR-T) have shown great promise to treat relapsed or refractory (r/r) B cell non-Hodgkin's lymphoma (B-NHL). However, comparison of their clinical outcomes has never been reported. This study investigated their efficacy and adverse events in B-NHL therapy. Six patients with r/r B-NHL were initially enrolled and infused with 28z or BBz CAR-T cells at a dose of 0.75-5 × 10 5 /kg. These CAR-T cells showed similar antitumor efficacies, with a complete response (CR) rate of 67% within 3 months. BBz CAR-T was well tolerated. However, severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in the 28z CAR-T cohort, resulting in the termination of further evaluation of 28z CAR-T. Three more patients were enrolled to investigate BBz CAR-T cells in-depth at an escalated dose (1 × 10 6 /kg). All cases achieved CR within 3 months, and only grade 1/2 adverse events occurred. This study suggests that 4-1BB is more beneficial for the clinical performance of CAR-T cells than CD28 in CD19-targeted B-NHL therapy, at least under our manufacturing process., (© 2019.)

Autologous T cells genetically modified with a chimeric antigen receptor (CAR) redirected at CD19 have potent activity in the treatment of B cell leukemia and B cell non-Hodgkin's lymphoma (B-NHL). Immunotherapies to treat multiple myeloma (MM) targeted the B cell maturation antigen (BCMA), which is expressed in most cases of MM. We developed a humanized CAR with specificity for BCMA based on our previously generated anti-BCMA monoclonal antibody. The targeting single-chain variable fragment (scFv) domain exhibited a binding affinity in the low nanomolar range, conferring T cells with high functional avidity. Redirecting T cells by this CAR allowed us to explore BCMA as an alternative target for mature B-NHLs. We validated BCMA expression in diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia. BCMA CAR T cells triggered target cell lysis with an activation threshold in the range of 100 BCMA molecules, which allowed for an efficient eradication of B-NHL cells in vitro and in vivo. Our data corroborate BCMA is a suitable target in B cell tumors beyond MM, providing a novel therapeutic option for patients where BCMA is expressed at low abundance or where anti-CD19 immunotherapies have failed due to antigen loss., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)