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Aim: To describe patient and treatment characteristics associated with bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer and their reference products in Japan. Methods: This retrospective observational study used an administrative claims database to identify patients with ≥1 biosimilar or reference product prescription from 2019 to 2022 for approved indications. Descriptive statistics were calculated. Results: Overall, 14–39% of biosimilar-prescribed patients initiated therapy with reference products. Biosimilar utilization significantly increased from 2019 to 2022. The most-commonly prescribed concomitant class of therapy with biosimilars was antineoplastic therapy. Conclusion: Reference products were most frequently prescribed among the Japanese cohorts, but substantial and increasing proportions received biosimilars over time. Future studies should extend our initial insights to assess biosimilar clinical outcomes in Japanese settings. Plain Language Summary This study examines the adoption of cancer biosimilar therapies in Japan from 2019 to 2022. Cancer biosimilars are complex treatments that closely resemble established cancer therapies already available in Japan. We looked into the characteristics of patients receiving three specific biosimilars – bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer. We also investigated where patients received biosimilar treatment, other therapies they received alongside biosimilars and the proportion of patients using these therapies each year during the study. Our analysis utilized data from the 'Medical Data Vision' database, which records care provided in hospitals across Japan. We analyzed patient demographics and treatment patterns, and compared different groups using statistics to identify significant differences. Notably, we observed that between 14 and 39% of patients initially started treatment with the original version of the drug on the market, known as the 'reference product,' before switching to the biosimilar. Furthermore, our findings revealed a significant increase in the use of biosimilars each year during the study period. Biosimilars were most-commonly used alongside chemotherapy drugs. These initial findings shed light on the patient population using cancer biosimilars in Japan and the treatment contexts in which they are utilized. Future research should delve deeper into aspects such as cost of care, patient survival, side effects and other pertinent factors related to the use of biosimilars in cancer care in Japan. Article highlights The use of oncology biosimilars in clinical practice in Japan is limited, at least partly, by the lack of evidence demonstrating real-world outcomes in Japanese patients. This retrospective observational study provides descriptive insights into the real-world use of bevacizumab, rituximab and trastuzumab biosimilars in Japan for colorectal cancer and non-small-cell lung cancer, B-cell non-Hodgkin's lymphoma and HER2-positive breast and gastric cancers, respectively. We observed significant increases in biosimilar utilization over time from 2019 to 2022. Across indications, from 14 to 39% of biosimilar-prescribed patients switched to the biosimilar after initiating therapy with the corresponding refence product. The most commonly prescribed concomitant class of therapy with biosimilars was antineoplastic therapy across each setting. This study has several limitations that should be noted, including that the Medical Data Vision hospital-based claims database has missing data for some variables, lacks detailed diagnosis and prognosis data (histology, Eastern Cooperative Oncology Group performance status, disease severity, etc.) and does not record deaths that occur outside the hospital. Initial real-world insights in Japan demonstrate comparable patient characteristics, treatment patterns and treatment duration between bevacizumab, rituximab and trastuzumab biosimilar and originator-treated patients. [ABSTRACT FROM AUTHOR]

Background: Bone marrow (BM) examination is an important investigation for staging or primary diagnosis of malignant lymphomas. The frequency of BM infiltration by lymphoma is quite variable. There are limited data available from developing countries on the pattern of BM involvement in patients of non-Hodgkin’s lymphoma (NHL). The aim of this study was to see the pattern of BM involvement by B-Cell NHL from a Tertiary Care Hospital in North India. Materials and Methods: All cases of B-cell NHL with BM involvement were included in this study. Peripheral blood smear, BM aspiration, and biopsy were performed for diagnosis and staging in all patients. Results: A total of 43 patients were diagnosed as B-cell NHL on BM aspiration and biopsy. The median age of our patients was 54.26 ± 15.07 years with a male: female ratio of 2.9:1. Twenty-four were indolent B-cell NHL cases and 19 patients had aggressive B-cell NHL. Indolent lymphomas such as SLL/CLL, MCL, FL, and marginal zone lymphoma are more common compared to aggressive NHL such as DLBCL and Burkitt’s lymphoma. Indolent lymphoma was more common in females than males (37.5% vs. 10.5%). The classical B-symptoms were present in 32.6% (n = 14). The BM was hypercellular in 62.8% of cases (n = 27) and cellular in 14% (n = 6). The pattern of BM biopsy involvement was diffuse in 65.1% (n = 28), interstitial in 23.3% (n = 10), and nodular in 11.6% (n = 5). Diffuse involvement of marrow was more frequent than nodular in aggressive lymphomas compared to indolent ones. Conclusions: In patients with B-cell NHL, BM involvement is more common in the indolent disease. The pattern of diffuse marrow involvement is more common in our region.

It has been suggested that the effect of coronavirus disease 2019 (COVID-19) booster vaccination in patients with B-cell non-Hodgkin's lymphoma (B-NHL) is inferior to that in healthy individuals. However, differences according to histological subtype or treatment status are unclear. In addition, there has been less research on patients who subsequently develop breakthrough infections. We investigated the effects of the first COVID-19 booster vaccination for patients with B-NHL and the clinical features of breakthrough infections in the Omicron variant era. In this study, B-NHL was classified into two histological subtypes: aggressive lymphoma and indolent lymphoma. Next, patients were subdivided according to treatment with anticancer drugs at the start of the first vaccination. We also examined the clinical characteristics and outcomes of patients who had breakthrough infections after a booster vaccination. The booster effect of the COVID-19 mRNA vaccine in patients with B-NHL varied considerably depending on treatment status at the initial vaccination. In the patient group at more than 1 year after the last anticancer drug treatment, regardless of the histological subtype, the booster effect was comparable to that in the healthy control group. In contrast, the booster effect was significantly poorer in the other patient groups. However, of the 213 patients who received the booster vaccine, 22 patients (10.3%) were infected with COVID-19, and 18 patients (81.8%) had mild disease; these cases included the patients who remained seronegative. Thus, we believe that booster vaccinations may help in reducing the severity of Omicron variant COVID-19 infection in patients with B-NHL. [ABSTRACT FROM AUTHOR]

Chimeric Antigen Receptor T-cells have improved the life expectancy of severely pretreated patients with aggressive hematological cancers; for this reason, therapy-related myeloid leukemias are becoming of great concern in this field, despite their clonal phylogenesis and mutational landscape have not been fully explored yet. This case discusses a 33-year-old man with refractory large B-cell lymphoma, treated with Chimeric Antigen Receptor T-cell (CAR-T) therapy as the 7th line of treatment. Despite a persistent partial response, the patient developed therapy-related acute myeloid leukemia (t-AML) six months post-CAR-T, revealing pre-existing clonal hematopoiesis. The myeloid malignancy exhibited an unusual hypocellular/dysplastic pattern, progressing to an established blast phase with cytopenia. Treatment with demethylating agents and BCL2 inhibitors proved ineffective, leading to t-AML with hyperleukocytosis and FLT3-ITD gain, resulting in the patient's death. This case underscores the impact of severe pretreatment and bone marrow impairment in CAR-T-associated t-AML, emphasizing their role over insertional mutagenesis. Furthermore, it highlights the retention of classic therapy-related leukemia characteristics, including the potential for acquiring FLT3 mutations and displaying dysplastic morphology in these secondary leukemias.

Abstract Background Aggressive B-cell non-Hodgkin’s lymphoma (B-NHL) patients often develop drug resistance and tumor recurrence after conventional immunochemotherapy, for which new treatments are needed. Methods We investigated the antitumor effects of CBL0137. In vitro, cell proliferation was assessed by CCK-8 and colony formation assay. Flow cytometry was performed to analyze cell cycle progression, apoptosis, mitochondrial depolarization, and reactive oxygen species (ROS) production. Autophagy was detected by transmission electron microscopy and mGFP-RFP-LC3 assay, while western blotting was employed to detect proteins involved in apoptosis and autophagy. RNA-sequencing was conducted to analyze the transcription perturbation after CBL0137 treatment in B-NHL cell lines. Finally, the efficacy and safety of CBL0137, rituximab, and their combination were tested in vivo. Results CBL0137, a small molecule anticancer agent that has significant antitumor effects in B-NHL. CBL0137 sequesters the FACT (facilitates chromatin transcription) complex from chromatin to produce cytotoxic effects in B-NHL cells. In addition, we discovered novel anticancer mechanisms of CBL0137. CBL0137 inhibited human B-NHL cell proliferation by inducing cell cycle arrest in S phase via the c-MYC/p53/p21 pathway. Furthermore, CBL0137 triggers ROS generation and induces apoptosis and autophagy in B-NHL cells through the ROS-mediated PI3K/Akt/mTOR and MAPK signaling pathways. Notably, a combination of CBL0137 and rituximab significantly suppressed B-NHL tumor growth in subcutaneous models, consistent with results at the cellular level in vitro. Conclusions CBL0137 has potential as a novel approach for aggressive B-NHL, and its combination with rituximab can provide new therapeutic options for patients with aggressive B-NHL. Video Abstract

Yttrium-90 ibritumomab tiuxetan (90YIT) is a radioimmunotherapy agent in which the radioisotope yttrium-90 is bound to ibritumomab via tiuxetan as a chelating agent, and is used for relapsed or refractory low-grade B-cell non-Hodgkin's lymphoma (rr-B-NHL). We conducted a joint study to evaluate the clinical outcome of 90YIT. The J3Zi study is composed of data from patients receiving 90YIT for rr-B-NHL from the top three institutions with 10 years of 90YIT treatment experience from October 2008 to May 2018 in Japan. The efficacy, prognostic factors and safety of 90YIT were retrospectively evaluated. Data from 316 patients were analyzed; the mean age was 64.6 years and the median number of prior treatments was 2. The median PFS was 3.0 years, the final OS rate was over 60%, and the median OS was not reached during the study period. Significant factors influencing PFS were sIL-2R ≤ 500 (U/mL) and no disease progression within 24 months of first treatment. Significant factors influencing OS were number of prior treatments ≤ 2 and sIL-2R ≤ 500 (U/mL). The PFS and OS rates were found to be significantly higher in the late half era (2013 to 2018) than in the early half era (2008 to 2013) during the study period. Prognosis following 90YIT treatment was improved in the late half era compared to the early half era. As treatment using 90YIT increased, administration of 90YIT shifted to the earlier treatment line. This may have contributed to the improvement of prognosis found in the late era. (UMIN000037105). [ABSTRACT FROM AUTHOR]

A wide range of histological as well as clinical properties are exhibited by B-cell non-Hodgkin's lymphomas. These properties could make the diagnostics process complicated. The diagnosis of lymphomas at an initial stage is essential because early remedial actions taken against destructive subtypes are commonly deliberated as successful and restorative. Therefore, better protective action is needed to improve the condition of those patients who are extensively affected by cancer when diagnosed for the first time. The development of new and efficient methods for early detection of cancer has become crucial nowadays. Biomarkers are urgently needed for diagnosing B-cell non-Hodgkin's lymphoma and assessing the severity of the disease and its prognosis. New possibilities are now open for diagnosing cancer with the help of metabolomics. The study of all the metabolites synthesised in the human body is called "metabolomics." A patient's phenotype is directly linked with metabolomics, which can help in providing some clinically beneficial biomarkers and is applied in the diagnostics of B-cell non-Hodgkin's lymphoma. In cancer research, it can analyse the cancerous metabolome to identify the metabolic biomarkers. This review provides an understanding of B-cell non-Hodgkin's lymphoma metabolism and its applications in medical diagnostics. A description of the workflow based on metabolomics is also provided, along with the benefits and drawbacks of various techniques. The use of predictive metabolic biomarkers for the diagnosis and prognosis of B-cell non-Hodgkin's lymphoma is also explored. Thus, we can say that abnormalities related to metabolic processes can occur in a vast range of B-cell non-Hodgkin's lymphomas. The metabolic biomarkers could only be discovered and identified as innovative therapeutic objects if we explored and researched them. In the near future, the innovations involving metabolomics could prove fruitful for predicting outcomes and bringing out novel remedial approaches. [ABSTRACT FROM AUTHOR]

It has been suggested that the effect of coronavirus disease 2019 (COVID-19) booster vaccination in patients with B-cell non-Hodgkin’s lymphoma (B-NHL) is inferior to that in healthy individuals. However, differences according to histological subtype or treatment status are unclear. In addition, there has been less research on patients who subsequently develop breakthrough infections. We investigated the effects of the first COVID-19 booster vaccination for patients with B-NHL and the clinical features of breakthrough infections in the Omicron variant era. In this study, B-NHL was classified into two histological subtypes: aggressive lymphoma and indolent lymphoma. Next, patients were subdivided according to treatment with anticancer drugs at the start of the first vaccination. We also examined the clinical characteristics and outcomes of patients who had breakthrough infections after a booster vaccination. The booster effect of the COVID-19 mRNA vaccine in patients with B-NHL varied considerably depending on treatment status at the initial vaccination. In the patient group at more than 1 year after the last anticancer drug treatment, regardless of the histological subtype, the booster effect was comparable to that in the healthy control group. In contrast, the booster effect was significantly poorer in the other patient groups. However, of the 213 patients who received the booster vaccine, 22 patients (10.3%) were infected with COVID-19, and 18 patients (81.8%) had mild disease; these cases included the patients who remained seronegative. Thus, we believe that booster vaccinations may help in reducing the severity of Omicron variant COVID-19 infection in patients with B-NHL.

Lymphocytoma cutis (LC) is one of the pseudolymphomas. It clinically and histopathologically resembles to cutaneous lymphomas due to the accumulation of lymphocytes. LC can be solitary characterized by only one nodule or disseminated, presenting as extensive lesions. It presents with soft and doughy or firm nodules, skin color, reddish brown, or reddish purple mainly on exposed area, such as the face. It has to be differentiated from Jessner's lymphocytic infiltrate of skin by histopathological and immunohistochemical examinations. Apart from treatment, follow-up of patients is crucial, as the condition can evolve into cutaneous lymphoma. We present a case of 54-year-old male, with lesions over the face, trunk, and both extremities diagnosed with disseminated LC.

Background: Aggressive B-cell non-Hodgkin's lymphoma (B-NHL) patients often develop drug resistance and tumor recurrence after conventional immunochemotherapy, for which new treatments are needed. Methods: We investigated the antitumor effects of CBL0137. In vitro, cell proliferation was assessed by CCK-8 and colony formation assay. Flow cytometry was performed to analyze cell cycle progression, apoptosis, mitochondrial depolarization, and reactive oxygen species (ROS) production. Autophagy was detected by transmission electron microscopy and mGFP-RFP-LC3 assay, while western blotting was employed to detect proteins involved in apoptosis and autophagy. RNA-sequencing was conducted to analyze the transcription perturbation after CBL0137 treatment in B-NHL cell lines. Finally, the efficacy and safety of CBL0137, rituximab, and their combination were tested in vivo. Results: CBL0137, a small molecule anticancer agent that has significant antitumor effects in B-NHL. CBL0137 sequesters the FACT (facilitates chromatin transcription) complex from chromatin to produce cytotoxic effects in B-NHL cells. In addition, we discovered novel anticancer mechanisms of CBL0137. CBL0137 inhibited human B-NHL cell proliferation by inducing cell cycle arrest in S phase via the c-MYC/p53/p21 pathway. Furthermore, CBL0137 triggers ROS generation and induces apoptosis and autophagy in B-NHL cells through the ROS-mediated PI3K/Akt/mTOR and MAPK signaling pathways. Notably, a combination of CBL0137 and rituximab significantly suppressed B-NHL tumor growth in subcutaneous models, consistent with results at the cellular level in vitro. Conclusions: CBL0137 has potential as a novel approach for aggressive B-NHL, and its combination with rituximab can provide new therapeutic options for patients with aggressive B-NHL. 3a3Ge1vW8eA3YTTebu-sV5 Video Abstract [ABSTRACT FROM AUTHOR]

Tafasitamab is an Fc-modified monoclonal antibody that binds to CD19, a cell-surface antigen that is broadly expressed on various types of B-cell non-Hodgkin's lymphoma (NHL). Antibody-dependent cellular cytotoxicity (ADCC), a key mode of action of tafasitamab, is mediated through the binding of tafasitamab's Fc region to FcγRIIIa receptors on immune effector cells and results in antitumor activity. Despite the proven clinical activity of tafasitamab in combination with lenalidomide in the treatment of diffuse large B-cell lymphoma (DLBCL), a higher number of immune cells in cancer patients may improve the activity of tafasitamab. Here, we characterized two ex vivo-expanded FcγRIIIa receptor—expressing cell types—γδ T and MG4101 natural killer (NK) cells—as effector cells for tafasitamab in vitro, and found that in the presence of these cells tafasitamab was able to induce ADCC against a range of NHL cell lines and patient-derived cells. We also explored the concept of effector cell supplementation during tafasitamab treatment in vivo by coadministering MG4101 NK cells in Raji and Ramos xenograft models of NHL. Combination treatment of tafasitamab and allogeneic MG4101 NK cells in these models demonstrated a survival benefit compared with tafasitamab or MG4101 monotherapy (Raji: 1.7- to 1.9-fold increase in lifespan; Ramos: 2.0- to 4.1-fold increase in lifespan). In conclusion, adoptive cell transfer of ex vivo-expanded allogeneic NK or autologous γδ T cells in combination with tafasitamab treatment may potentially be a promising novel approach to increase the number of immune effector cells and enhance the antitumor effect of tafasitamab. [ABSTRACT FROM AUTHOR]

Interstitial pneumonia (IP) is a significant adverse effect of chemotherapy in B-cell non-Hodgkin's lymphoma (NHL) patients. This study aimed to identify the clinical characteristics, risk factors, and treatment outcomes associated with IP in these patients. A retrospective review of 615 NHL patients treated at the Fourth Hospital of Hebei Medical University from 2016 to 2021 identified 50 patients with IP post-chemotherapy as the case group. A propensity score matched control group of 55 patients without pneumonia was established. Clinical profiles, risk factors, and treatment outcomes were evaluated. The IP incidence was 8.13% (50/615) in B-cell NHL patients. Multivariate analysis revealed liposomes, elevated lactate dehydrogenase (LDH), and erythrocyte sedimentation rate (ESR) as independent risk factors for IP. Receiver Operating Characteristic (ROC) curve analyses suggested that alterations in LDH and ESR could predict IP risk. The conclusion suggests that IP is associated with liposomal doxorubicin-induced lung injury and other cytotoxic chemotherapy, possibly due to Rituximab (RTX)-induced immune imbalance. Given the potential of IP with pulmonary infections, high-risk patients may need prophylactic antibiotics and appropriate corticosteroid therapy., Competing Interests: None., (AJCR Copyright © 2024.)

Zhi-He Liu,1 Lin Zhang,2 Fan-Jing Jing,1 Shu-Xin Xiao,1 Yan Gao,1 Hai-Yan Bian,1 Xia Zhao1 1Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People’s Republic of China; 2Laboratory of Molecular Diagnosis and Regenerative Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People’s Republic of ChinaCorrespondence: Xia ZhaoDepartment of Hematology, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Shinan District, Qingdao, 266000, Shandong, People’s Republic of ChinaTel/Fax +8653282911201Email alice-xia@163.comPurpose: The role of NLRP3 inflammasome in the progression of many diseases has been increasingly recognized. However, the function of this molecular assembly in the development and progression of B-cell non-Hodgkin’s lymphoma remains unclear.Patients and Methods: In this study, we investigated the polymorphisms in the NLRP3 inflammasome associated genes in 281 patients with B-cell non-Hodgkin’s lymphoma and 385 age- and gender-matched healthy controls.Results: We found that IL-18 (rs1946518) and NFκB-94 ins/del (rs28362491) contributed to susceptibility to B-cell non-Hodgkin’s lymphoma. Specifically, the allele “G” in IL-18 (rs1946518) and allele “ins” in NFκB-94 ins/del (rs28362491) were significantly associated with the risk of disease. The AA genotype of CARD8 (rs2043211) and the higher level of serum lactate dehydrogenase (LDH) led to statistically poorer B-cell non-Hodgkin’s lymphoma survival. Less frequent genotype TT of CARD8 (rs2043211) was observed in patients with higher LDH level, clinical stages III–IV of disease, and IPI 3– 5, although the relationship did not reach statistical significance. However, IPI is an independent prognostic factor for B-cell non-Hodgkin’s lymphoma.Conclusion: IL-18 (rs1946518) and NFκB-94 ins/del (rs28362491) gene polymorphisms appear to be the factors influencing the risk of B-cell non-Hodgkin’s lymphoma. CARD8 (rs2043211) polymorphisms are important factors for the survival of patients with this disease.Keywords: NLRP3, inflammasome, B-cell non-Hodgkin’s lymphoma, susceptibility, survival

Small nucleolar RNAs (snoRNAs) are responsible for post-transcriptional modification of ribosomal RNAs, transfer RNAs and small nuclear RNAs, and thereby have important regulatory functions in mRNA splicing and protein translation. Several studies have shown that snoRNAs are dysregulated in human cancer and may play a role in cancer initiation and progression. In this review, we focus on the role of snoRNAs in normal and malignant B-cell development. SnoRNA activity appears to be essential for normal B-cell differentiation and dysregulated expression of sno-RNAs is determined in B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, B-cell non-Hodgkin's lymphoma, and plasma cell neoplasms. SnoRNA expression is associated with cytogenetic/molecular subgroups and clinical outcome in patients with B-cell malignancies. Translocations involving snoRNAs have been described as well. Here, we discuss the different aspects of snoRNAs in B-cell malignancies and report on their role in oncogenic transformation, which may be useful for the development of novel diagnostic biomarkers or therapeutic targets. [ABSTRACT FROM AUTHOR]

B‐cell non‐Hodgkin's lymphoma (NHL) is a class of heterogeneous diseases with variable clinical outcomes. Immunosuppression is particularly common in the subtypes of lymphoma with poor prognosis, but the underlying mechanism remains unclear. Using a RT‐PCR array analysis, we have identified that glycosyltransferase 1 domain‐containing 1 (GLT1D1), an enzyme that transfers glycosyl groups to proteins, is highly upregulated in the incurable subtype of B‐cell NHL and in early relapse diffuse large B‐cell lymphoma. Analysis of clinical specimens revealed that GLT1D1 expression was positively correlated with the level of glycosylated programmed cell death‐ligand 1 (PD‐L1) in B‐cell NHL and that high GLT1D1 expression was associated with poor prognosis. Mechanistically, we showed that GLT1D1 transferred N‐linked glycans to PD‐L1, thus promoting the immunosuppressive function of glycosylated PD‐L1. Downregulation of GLT1D1 resulted in a decrease of glycosylated PD‐L1 and enhanced cytotoxic T‐cell function against lymphoma cells. In vivo, overexpression of GLT1D1 promoted tumor growth by facilitating tumor immune escape through increased levels of PD‐L1. Our work has identified GLT1D1 as a predictive biomarker for B‐cell NHL. It has also shown that this enzyme enhances PD‐L1 stabilization via N‐glycosylation, thus promoting immunosuppression and tumor growth. As such, GLT1D1 might be a novel therapeutic target for the treatment of B‐NHL.

A wide range of histological as well as clinical properties are exhibited by B-cell non-Hodgkin’s lymphomas. These properties could make the diagnostics process complicated. The diagnosis of lymphomas at an initial stage is essential because early remedial actions taken against destructive subtypes are commonly deliberated as successful and restorative. Therefore, better protective action is needed to improve the condition of those patients who are extensively affected by cancer when diagnosed for the first time. The development of new and efficient methods for early detection of cancer has become crucial nowadays. Biomarkers are urgently needed for diagnosing B-cell non-Hodgkin’s lymphoma and assessing the severity of the disease and its prognosis. New possibilities are now open for diagnosing cancer with the help of metabolomics. The study of all the metabolites synthesised in the human body is called “metabolomics.” A patient’s phenotype is directly linked with metabolomics, which can help in providing some clinically beneficial biomarkers and is applied in the diagnostics of B-cell non-Hodgkin’s lymphoma. In cancer research, it can analyse the cancerous metabolome to identify the metabolic biomarkers. This review provides an understanding of B-cell non-Hodgkin’s lymphoma metabolism and its applications in medical diagnostics. A description of the workflow based on metabolomics is also provided, along with the benefits and drawbacks of various techniques. The use of predictive metabolic biomarkers for the diagnosis and prognosis of B-cell non-Hodgkin’s lymphoma is also explored. Thus, we can say that abnormalities related to metabolic processes can occur in a vast range of B-cell non-Hodgkin’s lymphomas. The metabolic biomarkers could only be discovered and identified as innovative therapeutic objects if we explored and researched them. In the near future, the innovations involving metabolomics could prove fruitful for predicting outcomes and bringing out novel remedial approaches.

Small nucleolar RNAs (snoRNAs) are responsible for post-transcriptional modification of ribosomal RNAs, transfer RNAs and small nuclear RNAs, and thereby have important regulatory functions in mRNA splicing and protein translation. Several studies have shown that snoRNAs are dysregulated in human cancer and may play a role in cancer initiation and progression. In this review, we focus on the role of snoRNAs in normal and malignant B-cell development. SnoRNA activity appears to be essential for normal B-cell differentiation and dysregulated expression of sno-RNAs is determined in B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, B-cell non-Hodgkin’s lymphoma, and plasma cell neoplasms. SnoRNA expression is associated with cytogenetic/molecular subgroups and clinical outcome in patients with B-cell malignancies. Translocations involving snoRNAs have been described as well. Here, we discuss the different aspects of snoRNAs in B-cell malignancies and report on their role in oncogenic transformation, which may be useful for the development of novel diagnostic biomarkers or therapeutic targets.

Competing Interests: Competing interests: The authors declare no conflict of Interest.

Hepatitis C virus (HCV) is a global population problem due to its high prevalence, usually late diagnosis, the difficulties of treatment. In the prognosis of patients with HCV not only hepatic, but increasingly frequent of extrahepatic HCV manifestations, such as mixed cryoglobulinemia (CG), are important. Mixed CG is currently considered as a B-cell benign lymphoproliferative disorders. The role of HCV virus in the pathogenesis of lymphoproliferative diseases is confirmed by a large number of epidemiological studies, as well as by the effectiveness of antiviral therapy in patients with non-Hodgkin’s lymphoma (NHL). The purpose of the review was to provide an overview of recent literature data and the meta-analysis of epidemiological data explaining the role of HCV in the development of NHL. The review also discusses the treatment for HCV-associated NHL by antiviral therapy or other therapeutic options, such as chemotherapy.

Adult intussusception represents 5% of all intussusceptions. Primary gastro-intestinal lymphoma comprises 1%-4% of all gastro-intestinal malignancies 90% of them are B-cell non-Hodgkin's lymphoma (NHL). Most common NHL is diffuse large B-cell lymphoma accounts for 30-40%. Most common lymphoma causing intussusception is diffuse large B-cell lymphoma (DLBCL). We herein report a rare case of ileo-colic intussusception due to DLBCL in a 50-years-old male. Computed tomography showed ileo-colic intussusception with possibility of neoplastic etiology as a lead point. Hemicolectomy with ileo-colic anastomosis was done laparoscopically with post-operative chemotherapy. Subsequently, whole body positron emission tomography-computed tomography verified complete resolution of the malignancy. This study aims to present a rare case of ileo-colic intussusception due to non-Hodgkin's B-cell lymphoma in a patient with unusual clinical course and highlight the importance of not only the timely surgical intervention but also the significance of strict adherence to follow up and chemotherapy will completely eradicate the malignancy. [ABSTRACT FROM AUTHOR]

B‐cell non‐Hodgkin's lymphoma (NHL) is a class of heterogeneous diseases with variable clinical outcomes. Immunosuppression is particularly common in the subtypes of lymphoma with poor prognosis, but the underlying mechanism remains unclear. Using a RT‐PCR array analysis, we have identified that glycosyltransferase 1 domain‐containing 1 (GLT1D1), an enzyme that transfers glycosyl groups to proteins, is highly upregulated in the incurable subtype of B‐cell NHL and in early relapse diffuse large B‐cell lymphoma. Analysis of clinical specimens revealed that GLT1D1 expression was positively correlated with the level of glycosylated programmed cell death‐ligand 1 (PD‐L1) in B‐cell NHL and that high GLT1D1 expression was associated with poor prognosis. Mechanistically, we showed that GLT1D1 transferred N‐linked glycans to PD‐L1, thus promoting the immunosuppressive function of glycosylated PD‐L1. Downregulation of GLT1D1 resulted in a decrease of glycosylated PD‐L1 and enhanced cytotoxic T‐cell function against lymphoma cells. In vivo, overexpression of GLT1D1 promoted tumor growth by facilitating tumor immune escape through increased levels of PD‐L1. Our work has identified GLT1D1 as a predictive biomarker for B‐cell NHL. It has also shown that this enzyme enhances PD‐L1 stabilization via N‐glycosylation, thus promoting immunosuppression and tumor growth. As such, GLT1D1 might be a novel therapeutic target for the treatment of B‐NHL. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Monoclonal plasma cell proliferative disorders comprise a wide spectrum of diseases associated to clonal B-cell expansion. Serum protein electrophoretic profile (SPEP) and circulating free light chains (FLCs) levels are the mainstay of diseases management. Recently, soluble (s) Syndecan-1 (SDC1, CD138) produced by myeloma plasma cells has been suggested in the monitoring and follow-up of patients with myeloma. The aim of our study is to evaluate sCD138 in addition with FLCs and SPEP for the screening of patients with different evolutive disease pathways. PATIENTS AND METHODS: Sera from 73 patients with monoclonal gammopathy of undetermined significance (MGUS), 120 smoldering and 42 multiple myeloma (SMM and MM, respectively), 70 HCV-related mixed cryoglobulinemia (MC), 35 B-cell non-Hodgkin's lymphoma (B-NHL) and sera from 50 healthy donors (HD), were tested for sCD138, FLCs (assessed by means of ELISA and turbidimetric assay, respectively) and electrophoresis pattern (performed on Capillarys system) for the generation of a novel biomarker score (BS). RESULTS: Our results were grouped according to the two main lines of disease progression (vs. MM or B-NHL): in one group we found BS mean values of 0.2, 3.4, 5.3, 7.1 for HD, MGUS, SMM and MM, respectively; in the other group of 0.2, 4.4, 6.7 for HD, MC and B-NHL. CONCLUSIONS: We showed that BS mean values follow the ingravescence disease status towards the two main lines of progression to cancerous conditions; it could represent an additional useful tool in the management of screening and/or follow-up. [ABSTRACT FROM AUTHOR]

Objective: Perceived self-efficacy (PSE) is considered a foundation for effective self-care in the context of chronic disease and illness. In order to improve patient and caregiver knowledge about self-care in B-cell non-Hodgkin's lymphoma (NHL), we designed and delivered an online, patient-focused education activity. Educational impact on PSE was evaluated using a mixed quantitative/qualitative methodology. We report here on the qualitative characteristics of self-efficacy. Methods: We interviewed participants using open-ended questions based on a semi-structured interview guide. Interviews were audio-recorded and transcribed verbatim, and analysed using constant comparative method with software support (NVivo for Mac 11, QSR International). Results: In all, 12 people diagnosed with B-cell NHL were interviewed. Descriptive analysis showed that participants were able to summarise key education messages about B-cell NHL presented in the programme. Key themes linked to self-care knowledge and practice included normalisation of self-care, learning the hard way, everyone is different and being prepared. Participants described four key strategies linked to the notion of 'being prepared': (1) asking questions, (2) building relationships with oncologists, (3) developing/ maintaining a philosophy of life, and (4) connecting with others. These themes provide context for the experience of PSE and may also reflect beliefs that have implications for self-efficacy education. Conclusions: Interview data affirm PSE as a foundation of self-care and identify beliefs underpinning PSE. A dominant belief of 'being prepared' was sustained by four strategies that education content reinforced. Educators can use these insights to strengthen self-efficacy education interventions for patients with B-cell NHL and other types of cancer. [ABSTRACT FROM AUTHOR]

This article contains the detailed analysis of current approach to non-clinical and clinical development of monoclonal antibody biosimilars which is described in current guidelines of the European Medicines Agency (2012). Requirements of European regulatory authorities regarding evidence, which allows to demonstrate absence or presence of significant differences between biosimilar and original medicinal product are also discussed. There is the first publication of data from international clinical study of the 1st Russian rituximab biosimilar in patients with B-cell non-Hodgkin's lymphoma, which showed no differences with the reference medicinal product MabThera® in terms of efficacy and safety.

Background Infusion-related reactions (IRRs) are a major adverse event of rituximab. Objective To develop a prediction model for IRRs to rituximab among patients with B cell non- Hodgkin's lymphomas (B-NHL). Setting A 1000-bed university hospital in Tokyo. Methods Patients with B-NHL treated with rituximab at our institution from 2004 to 2014 were retrospectively analysed. Chills, fever, rash, nausea, asthenia, headache, cardiovascular symptoms, and respiratory symptoms of any grade, in association with rituximab infusion, were identified as IRRs. Risk factors for IRRs to rituximab found in the intergroup analysis were subsequently evaluated by using multivariate analysis. Main outcome measure Occurrence of IRRs to rituximab. Results A total of 140 patients with various types of B-NHL, including 74% with diffuse large Bcell lymphoma, were analysed. Among them, 55 and 85 patients were assigned to the IRR group and the non-IRR group, respectively. Indolent histological subtypes, bulky disease (>10 cm), B symptoms, higher serum soluble interleukin-2 receptor concentration, and bone marrow involvement were more common in the IRR group. The multivariate logistic regression analysis identified low-grade lymphomas [odds ratio (OR) 2.81, p = 0.017] and bulky disease (OR 2.52, p = 0.037) as independent risk factors for IRRs to rituximab. The incidence rates of IRRs to rituximab among patients with neither, one, or both of these risk factors were 26, 54, and 78%, respectively (χ2 = 16.4, p < 0.001). Conclusions A simple combination of histopathological subtype and bulkiness of disease could predict the risk of IRRs to rituximab among patients with B-NHL. [ABSTRACT FROM AUTHOR]

Treatments for relapsed/refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL) may be associated with an increased risk of second primary malignancies (SPMs). Currently available SPM incidence benchmarks are unreliable due to small sample sizes. The Cancer Analysis System (CAS), a population-level cancer database in England, was used to identify patients with incident B-cell NHL diagnosed during 2013–2018 with evidence of r/r disease. Incidence rates (IRs) of SPMs after r/r disease diagnosis were calculated per 1000 person-years (PYs) and stratified by age, sex, and SPM type. We identified 9444 patients with r/r B-cell NHL disease. Of those who were eligible for SPM analysis, nearly 6.0% (470/7807) developed at least one SPM after r/r disease diagnosis (IR: 44.7; 95% confidence interval [CI]: 40.9–48.9). Of note, 205 (2.6%) had a non-melanoma skin cancer (NMSC) SPM. IR of SPMs was the highest for patients with r/r chronic lymphocytic leukemia/small lymphocytic leukemia (80.0) and lowest for diffuse large B-cell lymphoma (DLBCL) (30.9). Patients with DLBCL had the shortest overall survival after r/r disease diagnosis. This real-world data study suggests that the IR of SPM among patients with r/r B-cell NHL is 44.7 per 1000 PY and that most SPMs diagnosed after r/r disease diagnosis are NMSCs, establishing a basis for the comparison of safety outcomes for new treatments being developed for r/r B-cell NHL. • 6.0% of r/r B-cell NHL patients have an SPM after r/r disease. • 10.6% of r/r B-cell NHL patients had a new primary malignancy between B-cell lymphoma diagnosis and r/r disease. • The incidence of first SPM in r/r B-cell NHL patients is 44.7/1000 PYAR. • NMSC is the most common type of SPM. • The rate of SPMs after r/r disease is highest in CLL/SLL NHL subtype patients. [ABSTRACT FROM AUTHOR]

The head and neck lymphomas are localized the most common in Waldeyer ring. These are include the most common B-cell non- Hodgkin’s lymphomas. Tonsillar involvement of non-Hodgkin’s lymphoma have been reported showing the average patient age of 59. Clinical findings in patients with tonsillar lymphoma involvement; sore throat, tonsillar enlargement, difficulty in swallowing, neck mass presence and visual complaints. This case, 32-year-old female patient presented with peritonsillar abscess. We performed tonsillectomy because of suspected the view. Pathologic examination revealed diffuse large cell B lymphoma has. B-cell non-Hodgkin’s lymphoma with Peritonsillar abscess and an early age presenting with tonsillar involvement was not found in another case in the literature.

The chaperonin containing t-complex polypeptide 1 (CCT) is known to mediate folding of proteins. CCT, subunit 8 (CCT8), is the θ subunit of CCT complex chaperonin. CCT8 has been reported to be dysregulated in several tumor tissues. In this study, we investigated the role of CCT8 in B-cell non-Hodgkin’s lymphoma (NHL). Clinically, the expression levels of CCT8 in reactive lymphoid hyperplasia (RLH) and B-cell NHL specimens were investigated using immunohistochemical analysis. We found that CCT8 was highly expressed in proliferating germinal center cells compared with the quiescent cells of the follicular mantle zone. Furthermore, CCT8 was highly expressed in progressive lymphomas than in indolent lymphomas. Kaplan-Meier curve showed that high expression of CCT8 was significantly associated with shorter overall survival in patients with diffuse large B-cell lymphoma. Moreover, we demonstrated that CCT8 could promote the proliferation of B-cell NHL cells. In addition, we found that CCT8 could accelerate the G1/S transition in B-cell NHL. Finally, we demonstrated that overexpression of CCT8 could reverse cell adhesion-mediated drug resistance (CAM-DR) phenotype. Our study may shed new insights into the important role of CCT8 in cancer development. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the expression levels of microRNA-503 (miR-503) and the tumor suppressor gene, kangai-1 (KAI1), in B-cell non-Hodgkin's lymphoma (B-NHL). A total of 45 patients with B-NHL (including 29 cases with stage III/IV disease and 16 cases with stage I/II disease) were enrolled in this study. In addition, 26 patients with reactive lymphoid hyperplasia (RLH) were enrolled as the control patients. Reverse transcription-quantitative polymerase chain reaction was performed in order to measure the expression levels of miR-503 in B-NHL and RLH tissues, and to detect the expression levels of miR-503 and KAI1 in peripheral blood samples. In addition, KAI1 expression levels in B-NHL and RLH tissues were detected using western blotting and immunohistochemical analysis. The expression levels of miR-503 were found to be significantly increased in the tissues and peripheral blood of B-NHL patients when compared with those in RLH patients (P<0.05). However, KAI1 was strongly expressed in RLH tissues and weakly expressed in B-NHL tissues. Furthermore, the expression levels of KAI1 were significantly decreased in the tissues and peripheral blood of B-NHL patients when compared with those in the tissues and peripheral blood of RLH patients (P<0.05). The expression levels of miR-503 in the tissues and peripheral blood of patients with stage III/IV B-NHL were significantly higher compared with those with stage I/II B-NHL (P<0.05). By contrast, the expression levels of KAI1 in stage III/IV B-NHL tissues were significantly higher compared with those in stage I/II B-NHL tissues (P<0.05). In conclusion, miR-503 was highly expressed, whereas KAI1 was poorly expressed, in the tissues and peripheral blood of B-NHL patients. Thus, miR-503 may have an application as a novel therapeutic and diagnostic marker in B-NHL patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We wished to assess the association between microRNA-21 (miR-21) and disease stage and treatment outcome in patients with B-cell non-Hodgkin's Lymphoma (B-NHL). PATIENTS AND METHODS: A total of consecutive 128 patients with B-NHL were enrolled; 30 healthy individuals served as controls. qPCR assay was utilized to quantify expression levels of miR-21 in peripheral blood mononuclear cells (PBMC; Ficoll isolation protocol). Expression of the miR-21 target, phosphatase and tensin homolog (PTEN), was assessed by Western blot analysis. RESULTS: miR-21 was overexpressed in PBMC of patients with B-NHL (p < 0.05 vs. healthy individuals). Furthermore, miR-21 expression levels were significantly higher in patients with the stage III/IV B-NHL (p < 0.05 vs. stage I/II B-NHL). After chemotherapy, miR-21 expression levels were significantly decreased in patients in complete remission and became comparable to those of healthy individuals. Also, miR-21 expression levels were lower in patients treated with chemotherapy combined with rituximab. There was a negative association between miR-21 over-expression and post-chemotherapy survival rates of the patients. Expression of PTEN was significantly lower in patients with B-NHL (p <0.05 vs. healthy individuals). CONCLUSIONS: Overexpression of miR-21 is associated with disease stage and treatment outcome of B-NHL. This potentially involves negative modulation of PTEN. [ABSTRACT FROM AUTHOR]

We report on the first well-tolerated and successful use of sofosbuvir-based therapy in a patient in whom chronic infection with hepatitis C had preceded the development of B-cell non-Hodgkin’s lymphoma. The patient had previously failed numerous attempts to clear the hepatitis C virus with traditional antiviral schedules. We demonstrate that sofosbuvir-based therapy resulted in cure of hepatitis C in a patient who had relapsed during combination therapy with an NS5A inhibitor, an NS3 protease inhibitor and ribavirin, as well as treatment failures to multiple courses of interferon-based therapy. This report also suggests that eradication of hepatitis C virus may result in the short-term prevention of B-cell non-Hodgkin’s lymphoma relapse. The findings from our case require further validation in future cohorts of patients. [ABSTRACT FROM AUTHOR]

It has been known that regulatory T (Treg) cells and mast cells (MCs) are involved in tumor immunity regulation, but the exact roles and mechanisms of Treg cells and MCs in B-cell non-Hodgkin's lymphoma (NHL) are incompletely defined. In the present study, we found that the number of Foxp3 Treg cells and CD117 MCs increased in B-cell NHL patients. Concomitantly, a high level of interleukin (IL)-9 was observed in the sera from B-cell NHL patients. Neutralizing IL-9 significantly inhibited tumor growth in the lymphoma model of murine, and this process was associated with down-regulation of Treg cells and MCs. Furthermore, IL-9 was also demonstrated to induce expression of MC-related genes and proliferation of MCs from the bone marrow stem cells. Collectively, our results indicate that Treg cell and MCs are involved in immunosuppression in B-cell NHL, and IL-9 is a key mediator of Treg cells and MCs in that process. These findings provide novel insight for the pathogenesis and possible therapeutic strategy of B-cell NHL. [ABSTRACT FROM AUTHOR]

Objective: Angiogenesis is critical for the development of tumors. Although vascular endothelial growth factor is a well-known proangiogenic factor, its impact on B-cell non-Hodgkin's lymphoma is not clear. The aim of this study is to evaluate vascular endothelial growth factor expression in subtypes of B-cell non-Hodgkin's lymphoma . Material and Method: Fifty-one patients with diagnoses of low and high grade B-cell non-Hodgkin's lymphoma were randomly selected and proper slides were immunostained with vascular endothelial growth factor antibody. The percentage of positive cells was recorded as the vascular endothelial growth factor score. A cut-off point was determined by using the median vascular endothelial growth factor score of all cases. The patients were subclassified as negative, weak or strong positive according to this cut-off point. Results: The study cohort included 26 women and 25 men, aged 5 to 82 years. The number of low-grade patients diagnosed as grade I follicular lymphoma and small lymphocytic lymphoma were 7 and 6; while the number of high grade patients diagnosed as diffuse large B-cell lymphoma and Burkitt's lymphoma were 29 and 9, respectively. Twenty-five patients (49.0%) showed strong and 10 patients (19.6%) showed weak vascular endothelial growth factor immunoreactivity, while 16 patients (31.4%) showed no staining. No statistically significant difference was found for vascular endothelial growth factor expression between subtypes of B-cell non-Hodgkin's lymphoma; as well as between low and high grade groups. Conclusion: Further studies in large and specific series are needed to determine the role of vascular endothelial growth factor receptor related pathways in the development and progression of B-cell non-Hodgkin's lymphomas. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and safety of radioimmunotherapy (RIT) with radioiodinated human/murine chimeric anti-CD20 monoclonal antibody rituximab (I-rituximab) for treating Korean patients with relapsed or refractory B-cell non-Hodgkin's lymphomas (NHL). All patients received unlabeled rituximab 70 mg immediately prior to the administration of a therapeutic dose (median dose: 7.3 GBq) of I-rituximab. The tumor response was evaluated 1 month later by contrast enhanced F-fludeoxyglucose positron emission tomography-computed tomography. Between May 2004 and October 2006, 24 patients received single treatment with I-rituximab. The overall response rate (ORR) was 29%; 46% (three complete responses, two partial responses (PR) for patients with low grade B-cell NHL (LGL) and 9% (one PR) for patients with diffuse large B-cell lymphoma (DLBCL). After a median follow-up of 55 months, the median progression-free survival (PFS) for all the patients was 2.2 months. The median overall survival (OS) was 11.3 months. There were statistically significant differences between the LGL and the DLBCL for the median PFS (4.5 months vs 1.3 months, respectively, P = 0.0007) and the median OS (30.3 months vs 6.5 months, respectively, P = 0.0295). Grades 3-4 thrombocytopenia and neutropenia occurred in 33% (8/24) and 21% (5/24) of the patients, respectively. RIT with I-rituximab seems to be effective and tolerable for patients with refractory LGL, although this treatment had modest activity in patients with refractory DLBCL. Further studies are warranted to determine the efficacy of I-rituximab for treating the patients with DLBCL. [ABSTRACT FROM AUTHOR]

Abstract: Background: Rituximab has provided a revolutionary contribution to the treatment of B-cell non-Hodgkin''s lymphomas (NHL). A high prevalence of hepatitis C virus (HCV) infection has been described in B-cell NHL patients. Cases of liver dysfunction in HCV-positive patients have been reported with rituximab-containing regimens. Aim: to evaluate the liver-related effects of rituximab-containing regimens on HCV-positive CD20-positive B-cell NHL patients. Patients and methods: Retrospective analysis of 104 consecutive patients. HCV status was determined, and development of hepatitis flares analysed. Results: Nine patients (8.6%) were HCV-positive. No correlation was shown between viral load and alanine transaminase levels. Three of the 9 HCV-positive, and none of the 95 HCV-negative developed hepatitis flares (p <0.001). At the 12-month follow-up hepatitis flare patients were alive and in remission for their haematological disease and no hepatitis flares, liver-related death had developed. Conclusions: HCV-positive status may represent a risk factor for the development of hepatic flares in B-cell NHL patients receiving rituximab-containing regimens. Despite the increase in liver function tests, there were no major clinical events. [Copyright &y& Elsevier]

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Abstract: Vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (b-FGF) have been described as essential cytokines in the regulation of angiogenesis. Their elevation has been associated with an unfavorable outcome in different neoplasms. However, their role in angiogenesis and proliferation in B-cell non-Hodgkin''s lymphoma (B-NHL) is unclear. Seventy cases of B-NHL besides 5 cases with reactive lymphadenitis were collected randomly and classified according to World Health Organization classification, Ann Arbor staging. They were subjected to immunostaining using VEGF, b-FGF, CD34, and Ki67 markers. There were a positive correlation between the proliferation and aggressiveness of the tumor as measured with Ki67 and both VEGF and b-FGF, and this was reflected on the stromal increase in microvessel density as measured by CD34. In conclusion, as the tumor becomes more aggressive, it also becomes independent of stromal paracrine factors by the establishment of an autocrine VEGF and b-FGF stimulation that can increase its angiogenesis and proliferation. [Copyright &y& Elsevier]

Anthracyclines, including doxorubicin, are widely used in the treatment of B-cell non-Hodgkin's lymphoma (NHL). However, their clinical potential is limited by their cardiotoxic adverse effects, which include cardiomyopathy and congestive heart failure. Anthracydine-induced cardiotoxicity is cumulative and irreversible. Liposomal doxorubicin has been developed with the aim of improving the therapeutic index of doxorubicin by reducing the drug's cardiotoxicity. Nevertheless, liposomal conjugation of doxorubicin results in preferential distribution of the drug in the tumor compared with normal tissue, maintaining its anti-tumor efficacy. Nonpegylated liposomal doxorubicin produced a promising response rate when substituted for conventional doxorubicin in the cydophosphamide, doxorubicin, vincristine and prednisolone regimen in the treatment of patients with NHL either at diagnosis or at relapse. The ability of nonpegylated liposomal doxorubicin to overcome excessive drug efflux due to P-glycoprotein (MDR-1) overexpression in NHL might confer on this drug a curative potential for patients with a bad prognosis (e.g., MDR-1 overexpressing, the elderly or frail). [ABSTRACT FROM AUTHOR]

Rituximab, a genetically engineered chimeric monoclonal antibody specifically binding to CD20, was the first antibody approved by the U.S. Food and Drug Administration for the treatment of cancer. Rituximab significantly improves treatment outcome in relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL). However, there are also some challenges for us to overcome: why ~50% of patients are unresponsive to rituximab in spite of the expression of CD20, and why some responsive patients develop resistance to further treatment. Although the antitumor mechanisms of rituximab are not completely understood, several distinct antitumor activities of rituximab have been suspected, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), apoptosis, and direct growth arrest. To counteract resistance to rituximab therapy, several strategies have been developed to: (a) augment theCDCeffect by increasing CD20 expression, heteroconjugating rituximab to cobra venom factor and C3b, and inhibiting membrane complement regulatory protein, especially CD59, function; (b) enhance the ADCC effect through some immunomodulatory cytokines and CR3-binding β-glucan; and (c) reduce the apoptotic threshold or induce apoptotic signaling on the tumor. Extensive studies indicate that rituximab combined with these approaches is more effective than a single rituximab approach. Herein, the mechanism of action of and resistance to rituximab therapy in B-cell NHL, in particular, the involvement of the complement system, are extensively reviewed. [ABSTRACT FROM AUTHOR]

To observe the clinical efficacy and toxic effects of Mabthera (rituximab) in combination with the CHOP (R-CHOP) regimen for treating invasive B-cell non-Hodgkin’s lymphoma.w A total of 45 patients with CD20 positive B-cell non-Hodgkin’s lymphoma were randomly divided into the R-CHOP (22 cases) and CHOP groups (23 cases for controls). They received the regimens of Mabthera in combination with CHOP or single CHOP therapy respectively. An appraisement of the curative effect could only be performed following 4 cycles of chemotherapy for the 45 patients. Follow-up was conducted to observe the conditions of survival. The rate of complete remission (CR) in the R-CHOP group was 68.2%, with a total effective rate of 81.8%, and in the CHOP group these rates were 34.8% and 78.3% respectively. There was a significant difference in comparing the CR rates between the two groups ( P < 0.05). The 1, 2 and 3-year overall survival (OS) rates of the RCHOP group were 90.9%, 81.8% and 77.3%, respectively. In the CHOP group, the OS rates were respectively 91.3%, 69.5% and 47.8%. The difference in the 3-year OS between the two groups was significant ( P < 0.05). The toxic effects of the two groups were mainly a slight and moderate bone marrow depression and a gastrointesinal reaction, with similar tolerable toxic effects in the two groups ( P > 0.05). Adverse effects related to the Mabthera infusions occurred in 6 cases of the R-CHOP group (27.2%). These effects lessened after symptomatic treatment. The therapeutic regimen of Mabthera, in combination with CHOP (R-CHOP) has an obvious curative effect for treating invasive B-cell non-Hodgkin’s lymphoma, with a favorable tolerance. It is highly recommended as the treatment of choice. [ABSTRACT FROM AUTHOR]

B-Cell Non-Hodgkin's Lymphomas comprise a biological heterogeneous group of haematological neoplasms with variable clinical behaviour. For clinical and prognostic purposes their classification has been based on several important parameters such as DNA content measured by flow cytometry. The present work tries to analyse the results and the recommendations published in the "Consensus Review of the Clinical Utility of DNA Flow Cytometry in Neoplastic Hematopathology" (Maine, 1992), and the studies published thereafter. [ABSTRACT FROM AUTHOR]