Prognosis Of non-Hodgkin Lymphoma Research Articles

Global burden, risk factors, and trends of non-Hodgkin lymphoma: A worldwide analysis of cancer registries.

Non-Hodgkin lymphoma (NHL) accounts for 90% of all malignant lymphomas. This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of NHL by sex, age, and country. Data from 185 countries globally were used for analysis. NHL incidence and mortality were collected via the GLOBOCAN (2020), CI5 series I-X, WHO mortality database, the Nordic Cancer Registries, and the SEER Program. The WHO Global Health Observatory provided country-level, age-standardized prevalence of lifestyle and metabolic risk factors. Trends were examined and reported based on average annual percentage change (AAPC) calculated using Joinpoint regression analysis. Incidence and AAPC are based on data for the last 10 years across countries. Globally, age-standardized incidence and mortality rates for NHL were recorded at 5.8 and 2.6 per 100,000 individuals, respectively. At country-level, NHL incidence was significantly associated with various factors, including HDI (Human Development Index), GDP per capita, prevalence of tobacco and alcohol consumption, sedentary lifestyle, obesity, hypertension, diabetes and hypercholesterolaemia. Rising trend in NHL incidence was observed, with the highest increase recorded in Estonia (AAPCmale = 4.15, AAPCfemale = 5.14), Belarus (AAPCfemale = 5.13), and Lithuania (AAPCfemale = 4.68). While overall NHL mortality has been decreasing, certain populations experienced increased mortality over the decade. In Thailand, AAPC for mortality was 31.28% for males and 30.26% for females. Estonia saw an AAPC of 6.46% for males, while Slovakia experienced an AAPC of 4.24% for females. Colombia's AAPC was 1.29% for males and 1.51% for females. This study indicates a rising trend of NHL incidence over the past decade- particularly in developed countries, older males, and younger populations. Further research should investigate deeper insights into specific etiology and prognosis of NHL across subtypes, and potential contributors towards these epidemiologic trends.

Accumulation of circulating myeloid-derived suppressor cell subsets: predicting poor clinical efficacy and prognosis through T cell suppression in non-Hodgkin's lymphoma.

Myeloid-derived suppressor cells (MDSCs) are implicated in the regulation of immune responses closely associated with poor clinical outcomes in cancer. However, the MDSC subtypes in non-Hodgkin's lymphoma (NHL) have not been systematically investigated. So, we investigated the percentage of MDSC subsets in 78 newly diagnosed NHL patients by flow cytometry. The results showed that all MDSC subsets increased in NHL patients compared with healthy donors. Notably, MDSCs, monocytic MDSCs, and CD14 + CD66b + MDSCs significantly increased in NHL patients compared with those with lymphadenitis donors. polymorphonuclear MDSCs (PMN-MDSCs), early-stage MDSCs (e-MDSCs), and the International Prognostic Index were independent risk factors for poor clinical efficacy and were involved in constructing the nomogram for predicting clinical efficacy. Progression-free survival (PFS) was significantly shorter in patients with high level of MDSC subsets, and PMN-MDSCs emerged as an independent prognostic factor for PFS. PMN-MDSCs, e-MDSCs, and the International Prognostic Index were involved in constructing the nomogram for predicting PFS. Patients with a higher percentage of MDSCs, PMN-MDSCs, e-MDSCs, and CD14 + CD66b + MDSCs experienced a shorter overall survival compared with those with lower percentages. In addition, research on mechanisms found that T cell function was suppressed and mediated by the expansion of MDSCs via involving arginase-1 and interleukin-10 in vitro and in vivo. In conclusion, our study demonstrates that the increased circulating MDSC subsets predict poor clinical efficacy and prognosis in NHL, potentially involving T cell suppression through MDSC subset expansion. These findings indicate the potential of MDSC subsets as comprehensive diagnostic, prognostic biomarkers, and therapeutic targets for NHL.

The Lymphoma Epidemiology of Outcomes cohort study: Design, baseline characteristics, and early outcomes.

To address the current and long-term unmet health needs of the growing population of non-Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18-99). Participants came from 49 US states and included 538 Black/African-Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 years, and 1513 rural residents. At study baseline, we abstracted clinical, pathology, and treatment data; banked serum/plasma (N = 5883, 76.0%) and germline DNA (N = 5465, 70.7%); constructed tissue microarrays for four major NHL subtypes (N = 1189); and collected quality of life (N = 5281, 68.3%) and epidemiologic risk factor (N = 4489, 58.0%) data. Through August 2022, there were 1492 deaths. Compared to population-based SEER data (2015-2019), LEO participants had a similar distribution of gender, AA race, Hispanic ethnicity, and NHL subtype, while LEO was underrepresented for patients who were Asian and aged 80 years and above. Observed overall survival rates for LEO at 1 and 2 years were similar to population-based SEER rates for indolent B-cell (follicular and marginal zone) and T-cell lymphomas, but were 10%-15% higher than SEER rates for aggressive B-cell subtypes (diffuse large B-cell and mantle cell). The LEO cohort is a robust and comprehensive national resource to address the role of clinical, tumor, host genetic, epidemiologic, and other biologic factors in NHL prognosis and survivorship.

The Latest Research Progress of Selinexor in the Treatment of Non-Hodgkin Lymphoma --Review

Non-Hodgkin lymphoma (NHL) is a common lymphoid hematological malignancy, the treatment and prognosis of NHL have always been the focus of clinical attention. Chemotherapy is the main first-line treatment, but there is still no effective treatment for patients with poor response to chemotherapy, recurrence or progression within a short period of time after treatment, and new and effective drugs need to be developed clinically. As the only clinically validated oral selective inhibitor of nuclear export (SINE), Selinexor has been approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma and multiple myeloma, clinical attempts are being made to apply it to the treatment of other hematological malignancies.This article reviews the anti-tumor mechanism of Selinexor and the latest research progress in its application in NHL, and provides ideas for a more diverse, standardized and effective applications of Selinexor in NHL.

The Potential utility of fourier transform infrared spectroscopy for the diagnosis and the prognosis of non-hodgkin lymphoma

Background: Fourier Transform Infrared (FTIR) can detect slight change in the biochemical global composition in samples taken from patients with Non-Hodgkin’s lymphomas (NHL) including changes in carbohydrates, proteins, nucleic acid, lipids or even water. These small changes might serve early detection before any morphological changes occur. Patients and methods: The study included samples from (30) patients with diffuse large B-cell lymphomas (DLBCL) and samples from (33) healthy controls. The serum samples were analyzed using FTIR spectroscopy and the resulted data were analyzed using support vector machine (SVM) learning. Results: Ranges 1240-1190 cm-1 and 1140-1000 cm-1 had the best true positive, false negative and accuracy results. True negative, false positive, specificity and precision were best seen in Range 1580-1480 cm-1 and sensitivity was best seen in Range 3500-2800 cm-1. Ranges 1240-1190 cm-1 and 1140-1000 cm-1 represent frequencies that are assigned to bonds found in nucleic acids. Conclusion: FTIR spectra ranges that could be recommended to be used as diagnostic and prognostic tool for DLBCL patients are 3500-2800,1580-1480 and 1240-1000 cm-1. The finding that the most important changes occurs in the nucleic acids may has therapeutic implication.

Phase I Study: Safety and Efficacy of an Ex Vivo-Expanded Allogeneic Natural Killer Cell (MG4101) with Rituximab for Relapsed/Refractory B Cell Non-Hodgkin Lymphoma

The prognosis of non-Hodgkin lymphoma (NHL) remains poor, with an unmet need for novel therapies. MG4101, an ex vivo-expanded allogeneic natural killer (NK) cell, can enhance rituximab antibody-dependent cytotoxicity in relapsed/refractory (r/r) B cell non-Hodgkin lymphoma. This study assessed the safety and efficacy of MG4101 plus rituximab for patients with r/r NHL. Patients received escalating doses of i.v. MG4101 plus rituximab every 2 weeks. IL-2 was administered s.c. after MG4101 treatment. Fludarabine plus cyclophosphamide was administered i.v. before rituximab treatment in cycles 1, 3, and 5. A 3+3 design was used to determine the maximum tolerated dose (MTD) and maximum feasible dose. Assessments were performed over a 6-cycle period, with an extended maintenance period of up to 8 cycles. Nine patients received 3 different doses of MG4101 and rituximab. MTD could not be determined because of the absence of dose-limiting toxicity. Treatment-related adverse events, mostly grade 1 or 2, occurred in 89% of patients. Only 1 patient experienced grade 1 cytokine release syndrome. MG4101 persisted for at least 7 days in 7 patients. Four patients achieved a partial response and 1 patient attained a complete response, for an overall response rate of 55.6%. Two patients showed prolonged responses and low exhaustion marker levels in T cells. For allogeneic NK cell therapy, strategies including the use of the high-affinity hFcγRIIIaV158 variant of the KIR B/x haplotype with lymphodepleting chemotherapy may be promising options for improving clinical efficacy in the antibody combination therapeutic setting as an off-the-shelf product. MG4101 plus rituximab presented a favorable safety profile and overall response rate in patients with r/r NHL.

The Clinical and Translational Exploration of the Role of S1P/SPHK1 Pathway in Non-Hodgkin Lymphoma with Obesity

Non-Hodgkin lymphoma (NHL) is among the top 10 malignant tumors in incidence and mortality. Accumulating evidence indicates that obesity may influence the prognosis of several types of lymphoma, but the underlying mechanism is largely unknown for contributing to the poor prognosis or the aggressiveness of NHL. Obesity can result in abnormal lipid metabolism, especially abnormal sphingolipid metabolism. Existing data indicate the carcinogenetic role of Sphingosine-1-phosphate (S1P)/ sphingosine kinases (SPHK) signaling, we hypothesized that SIP/SPHK signaling played an important role in lymphomagenesis. To test the hypothesis that obesity deteriorate the prognosis of NHL, we retrospectively investigated a cohort of 2094 patients who were diagnosed with lymphoma in the First Hospital of Jilin University from Jun 1st, 2011 to Jun 1st 2021. These patients were categorized into high Body Mass Index (BMI, defined as BMI≥25) group and low BMI (defined as BMI<25) group. The demographic information and imaging evidence of disease progression were extracted and analyzed. Survival data were follow-up till Jun 1st 2021. Progression-free survival (PFS) and overall survival (OS) of three main subtypes of lymphomas (namely Diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL], peripheral T-cell lymphoma-not otherwise specified [PTCL-NOS]) in this cohort were compared with the time-to-event analysis. High BMI group had a negative impact on PFS and OS in all three groups (DLBCL [P < 0.05], FL [P < 0.05], and PTCL-NOS [P < 0.05]).（A） To investigate S1P signaling, we performed an IHC study to determine the levels of S1P in the tissue array-samples from various human lymphomas. By computer-imaging analysis, significantly increased S1P levels were detected in the tissues from DLBCL, follicular lymphoma (FL), and peripheral T-cell lymphoma (PTCL). Using a web-based database, Gene Expression Omnibus (GEO), the high throughput gene expression was profiled for SPHK1 and SPHK2 in the lymphomas (DLBCL, FL, and PTCL) and the respective normal controls. Significantly up-regulated expression of SPHK1 was found in DLBCL (n = 55) versus centroblast B-cells (n = 7), in FL (n = 14) versus normal B-cells (n = 5), and in PTCL (n = 80) versus normal T cells (n =10). Significantly up-regulated expression of SPHK2 were also detected in DLBCL but not in FL and PTCL in comparison with their respective normal controls.（B-C） To further investigate the potential mechanism of S1P-S1P receptors mediated lymphogenisis, we employed two human lymphoma cell lines (HH for T cell lymphoma and SU-DHL-4 for B cell lymphoma) for verification. The S1P mediated down-regulation of YAP phosphorylation was found in both HH cells and SU-DHL-4 cells. WB showed up-regulated S1PR1 and S1PR3, and down-regulated S1PR2, consistent with the qPCR results. Three S1PR inhibitors (W146 for S1PR1, CAY10444 for S1PR3, and FTY720 for S1PR1-5) were selected to confirm the hypothesis that S1P signaling could mediate the HIPPO pathway in lymphoma cells. XTT cell viability assay and a trans-well assay as well as WB were further performed to investigate cell proliferation, migration, and EMT. Consistently, blockage of S1PR1 and/or S1PR3 significantly inhibited the S1P induced cell proliferation and migration, down regulated the Cyclin D1 expression, and attenuated the alterations of E-cadherin/Vimentin in both HH cells and SU-DHL-4 cells. These results indicated that blockage of S1PR1 and/or S1PR3 significantly attenuated the S1P-induced decreases of YAP phosphorylation in both HH cells and SU-DHL-4 cells.（D） In conclusion, the NHL patients with obesity have a poor PFS and OS, which is associated with the elevated S1P-SPHK1 signaling. S1P-S1PR1/S1PR3-YAP signaling mediates lymphomagenesis contributing to tumor aggressive growth. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Research Progress of Transmembrane Protein Abnormality in Non-Hodgkin's Lymphoma --Review

Transmembrane protein, also known as integral membrane protein, can be distributed in the lipid bilayer or across the entire membrane, and it plays an important role in cell signal transduction. It has been discovered that multiple transmembrane proteins are involved in the regulation of tumor signals. Recent studies have revealed that the abnormal expression of some transmembrane protein is closely related to the occurrence, development and prognosis of non-Hodgkin's lymphoma (NHL), including programmed cell death protein 1 (PD-1), TMEM30A, NOTCH1, TOLL-like receptor (TLR), sphingosine-1-phosphate receptor, TRAIL, etc. The study on these transmembrane proteins and related genes has important clinical significance for the treatment and prognosis of NHL, and it may become a new therapeutic target. At present, there have been some research results in this field at home and abroad. This article reviewed the research progress of transmembrane protein that has inhibitory effects on NHL in recent years.

Management of Aggressive Non-Hodgkin Lymphomas in the Pediatric, Adolescent, and Young Adult Population: An Adult vs. Pediatric Perspective.

Simple SummaryThis review details the diagnosis and treatment of primary non-Hodgkin lymphoma (NHL) in the pediatric and adolescent population. We also describe treatment modalities such as hematopoietic stem cell transplantation for relapsed or refractory NHL in patients that fail or do not respond to the initial therapy. We then detail the current advancements in treatment for patients that fail initial therapy such as CAR T-cell therapy, the use of immunotherapy that target surface makers on malignant cells and highlight areas where further research is needed. The purpose of our review is to inform the pediatric oncology community in regard to the various types of NHLs and emphasize areas where the science is evolving in the treatment of primary, relapsed or refractory disease.Non-Hodgkin lymphoma (NHL) is a broad entity which comprises a number of different types of lymphomatous malignancies. In the pediatric and adolescent population, the type and prognosis of NHL varies by age and gender. In comparison to adults, pediatric and adolescent patients generally have better outcomes following treatment for primary NHL. However, relapsed/refractory (R/R) disease is associated with poorer outcomes in many types of NHL such as diffuse large B cell lymphoma and Burkitt lymphoma. Newer therapies have been approved in the use of primary NHL in the pediatric and adolescent population such as Rituximab and other therapies such as chimeric antigen receptor T-cell (CAR T-cell) therapy are under investigation for the treatment of R/R NHL. In this review, we feature the characteristics, diagnosis, and treatments of the most common NHLs in the pediatric and adolescent population and also highlight the differences that exist between pediatric and adult disease. We then detail the areas of treatment advances such as immunotherapy with CAR T-cells, brentuximab vedotin, and blinatumomab as well as cell cycle inhibitors and describe areas where further research is needed. The aim of this review is to juxtapose established research regarding pediatric and adolescent NHL with recent advancements as well as highlight treatment gaps where more investigation is needed.

ZCL-082, a boron-containing compound, induces apoptosis of non-Hodgkin's lymphoma via targeting p90 ribosomal S6 kinase 1/NF-κB signaling pathway

IntroductionDespite the rapid progress in the diagnosis and treatment, the prognosis of some types of non-Hodgkin's lymphoma (NHL), especially those with double-hit or double-expressor genotypes, remains poor. Novel targets and compounds are needed to improve the prognosis of NHL. MethodsWe investigated the effect of ZCL-082, a novel boron-containing compound with anti-proliferating activity against ovarian cancer cells, on NHL cells and human peripheral blood mononuclear cells by CCK-8 assay, Annexin V/PI double staining assay, RH123/PI double staining, Western blot, and immunohistochemistry. NF-κB pathway activity was analyzed using luciferase reporter gene assay and RT-PCR. The location of p65 was detected by immunofluorescence and nuclear/cytoplasmic fractionation assay. Immunoprecipitation and chromatin immunoprecipitation assays were used to detect the binding between p65 and p300. CETSA and molecular docking assay were carried out to test the interaction between ZCL-082 and p90 ribosomal S6 kinase 1 (RSK1). Kinase reaction was conducted to examine the inhibition of RSK1 kinase activity by ZCL-082. ResultsWe found that ZCL-082 can induce the apoptosis of various NHL cell lines in vitro and in vivo. ZCL-082 significantly inhibits TNFα- or LPS-induced NF-κB activation without disturbing TNFα-induced IκBα degradation or the nuclear translocation and DNA-binding ability of p65. However, ZCL-082 markedly suppresses the phosphorylation of p65 on Ser536 and the interaction between p65 and p300. The overexpression of the phosphomimetic mutant of p65 at Ser536 partially abrogates ZCL-082-induced cell death. We further found that ZCL-082 directly binds to and inhibits the activity of RSK1. RSK1 can phosphorylate RelA/p65 on Ser536 and its overexpression is associated with the poor prognosis of lymphoma. The overexpression of RSK1 partially rescues ZCL-082-induced cell death. Molecular docking studies show that ZCL-082 fits well with the N-terminal kinase domain of RSK1. Furthermore, the combination of ZCL-082 and BCL-2 inhibitor ABT-199 has a synergistic apoptosis-inducing effect against double-hit lymphoma cell line OCI-Ly10. DiscussionWe found that ZCL-082 is a highly promising anti-lymphoma compound that targets RSK1 and interferes with the RSK1/NF-κB signaling pathway. The combination of ZCL-082 with BCL-2 inhibitor may represent a novel strategy to improve the outcome of double-hit or double-expressor lymphoma.

The expression of heat shock protein A12B (HSPA12B) in non-Hodgkin's lymphomas.

BackgroundHeat shock protein A12B (HSPA12B) plays a considerable protective role for cells, tissues, and organs against various noxious conditions. However, the expression of HSPA12B in cancer biology remains controversial. This study aimed to investigate the expression of HSPA12B and its role in cell adhesion mediated drug resistance (CAM-DR) of non-Hodgkin’s lymphoma (NHL).MethodsIn this study, the expression of HSPA12B in NHL was determined by immunohistochemical, and the effect of HSPA12B expression on the prognosis of NHL was analyzed by Kaplan–Meier curves. Then, the transfection technique was used to research the effect of HSPA12B in cell apoptosis. The most important was to study the expression changes of HSPA12B in the adhesion model and the effect of overexpression of HSPA12B on CAM-DR.ResultsWe analyzed the relationship between the expression levels of HSPA12B and clinical parameters in NHL. The expression of HSPA12B was directly related to the different NHL variants. We overexpressed HSPA12B in 2 NHL cell lines and found a subsequent reduction in apoptosis. More specifically, we used an adhesion assay to demonstrate that HSPA12B expression was induced in NHL cells when they adhered to fibronectin (FN) or bone marrow stroma cells (BMSCs). Finally, it was revealed that HSPA12B overexpression enhances CAM-DR.ConclusionsOur data suggest that HSPA12B may play a functional role in CAM-DR and is thus a potential novel target for NHL treatment.

The Influence of Interleukin-2 Gene Polymorphisms on the Risk and Clinical Outcome of Non-Hodgkin Lymphoma.

Polymorphisms in the IL-2 gene are associated with various diseases and cancers including non-Hodgkin lymphoma (NHL). The aim of the study is to assess the impact of IL-2 genetic polymorphisms [- 330T/G (rs2069762) and + 114T/G (rs2069763)] on the susceptibility and prognosis of NHL. Sixty patients with NHL as well as 60 age and sex matched healthy control subjects are included in this study. IL-2 genotypes were determined by Polymerase Chain Reaction-Restriction Fragment length Polymorphism assay (PCR-RFLP). Our study revealed that both IL-2 rs2069762 and rs2069763 gene polymorphisms are associated with increased risk of developing NHL; OR = 3.609 (95% CI = 1.527-8.417) and 4.142 (95% CI = 1.637-10.538) respectively. Moreover, the simultaneous presence of both polymorphisms is associated with about 6 fold increased risk of developing NHL. Also, IL-2 rs2069762 and rs2069763 gene polymorphisms increase the risk of unfavorable prognosis with OR = 17.300 (95% CI = 3.392-87.725) and 10.424(95% CI = 1.870-58.413) respectively. These findings suggest that IL-2 (rs2069762) and (rs2069763) gene polymorphisms could be involved in the development of NHL.

IBCL-380: Clinical Features of Non-Hodgkin Lymphomas with Primary Involvement of Peripheral Lymph Nodes in an Elderly Population

Context: Non-Hodgkin lymphoma (NHL) is one of the most common types of cancer. It can be diagnosed at any age; however, it is more frequently diagnosed among elderly patients. Usually, age over 60 years is associated with an unfavorable prognosis mainly due to multiple comorbidities and poor performance status. More frequently, the onset of NHL starts with the primary involvement of the lymph nodes (LN) in 52–70% of cases. An important role in NHL prognosis, in addition to the immunohistochemical and molecular features, is played by the primary site of involvement. Objective: The study aims to emphasize the clinical aspects of NHL with primary LN involvement in patients over 60 years of age. Materials and Methods: A retrospective study was conducted on 78 patients with NHL with primary LN involvement aged from 60 to 84 years, examining the clinical features and the evolution of each case. Results: It was found that NHL with onset in the LN had developed more frequently in people aged between 60 to 70 years (73.1%). NHL more often developed primarily in the peripheral LN (84.7%) and less frequently in the mediastinal LN (6.4%) and abdominal LN (8.9%). Aggressive NHL predominated (59.0%), but indolent NHL in 41.0% was seen more frequently in cases of affection to the cervical LN (47.4%), inguinal LN (41.7%), and abdominal LN (42.9%). In most of the cases (73.8%), the tumor process spread to the regional LN. Extranodal metastases occurred more frequently in the liver (47.7%), bone marrow (BM) (43.2%), and spleen (29.5%). BM involvement was found predominantly in indolent NHL (53.1%). In aggressive NHL, BM metastases were identified in only 4.3% of cases. The 5-year OS of patients of the study group was low at 31.2%. Conclusions: NHL with primary LN involvement developed more frequently in people aged 60–70 years. The onset of NHL occurred more often in the peripheral LN (84.7%) and less frequently in the mediastinum (6.4%) and abdominal LN(8.9%). The ratio of aggressive NHLs to indolent NHLs was 59% vs. 41%. Extranodal metastases affect mainly the liver(47.7%), bone marrow (43.2%), and spleen(29.5%). BM involvement occurred more frequently in indolent NHL(53.1%). Five-year OS in the study group was reduced (31%), being influenced by comorbidities. Non-Hodgkin lymphoma (NHL) is one of the most common types of cancer. It can be diagnosed at any age; however, it is more frequently diagnosed among elderly patients. Usually, age over 60 years is associated with an unfavorable prognosis mainly due to multiple comorbidities and poor performance status. More frequently, the onset of NHL starts with the primary involvement of the lymph nodes (LN) in 52–70% of cases. An important role in NHL prognosis, in addition to the immunohistochemical and molecular features, is played by the primary site of involvement. The study aims to emphasize the clinical aspects of NHL with primary LN involvement in patients over 60 years of age. A retrospective study was conducted on 78 patients with NHL with primary LN involvement aged from 60 to 84 years, examining the clinical features and the evolution of each case. It was found that NHL with onset in the LN had developed more frequently in people aged between 60 to 70 years (73.1%). NHL more often developed primarily in the peripheral LN (84.7%) and less frequently in the mediastinal LN (6.4%) and abdominal LN (8.9%). Aggressive NHL predominated (59.0%), but indolent NHL in 41.0% was seen more frequently in cases of affection to the cervical LN (47.4%), inguinal LN (41.7%), and abdominal LN (42.9%). In most of the cases (73.8%), the tumor process spread to the regional LN. Extranodal metastases occurred more frequently in the liver (47.7%), bone marrow (BM) (43.2%), and spleen (29.5%). BM involvement was found predominantly in indolent NHL (53.1%). In aggressive NHL, BM metastases were identified in only 4.3% of cases. The 5-year OS of patients of the study group was low at 31.2%. NHL with primary LN involvement developed more frequently in people aged 60–70 years. The onset of NHL occurred more often in the peripheral LN (84.7%) and less frequently in the mediastinum (6.4%) and abdominal LN(8.9%). The ratio of aggressive NHLs to indolent NHLs was 59% vs. 41%. Extranodal metastases affect mainly the liver(47.7%), bone marrow (43.2%), and spleen(29.5%). BM involvement occurred more frequently in indolent NHL(53.1%). Five-year OS in the study group was reduced (31%), being influenced by comorbidities.

Prediction of survival in non-Hodgkin lymphoma based on markers of systemic inflammation, anemia, hypercoagulability, dyslipidemia, and Eastern Cooperative Oncology Group performance status

AbstractBackgroundThe International Prognostic Index and its modifications are used to estimate prognosis in non-Hodgkin lymphoma. However, the outcome is often different in patients with similar index scores.AimThe aim of this study was to elaborate a prognostic model for patients with mature B-cell non-Hodgkin lymphoma using a combination of predictive markers.Material and methodsThe study included 45 patients with mature B-cell non-Hodgkin lymphoma. Before the administration of treatment, clinical and laboratory parameters were measured. After the 35-month follow-up period, overall survival was studied in relation to the data obtained at initial examination.ResultsWe revealed nine adverse predictive markers for overall survival of enrolled patients: Eastern Cooperative Oncology Group (ECOG) performance status &gt;1; erythrocyte sedimentation rate &gt;30 mm/h; levels of hemoglobin &lt;120 g/L, fibrinogen ≥6 g/L, interleukin-6 ≥2 pg/mL, tumor necrosis factor ≥1.45 pg/mL, soluble fibrin monomer complexes &gt;4 mg/dL, high-density lipoprotein cholesterol &lt;1.03 mmol/L in men, and &lt;1.29 mmol/L in women; and short activated partial thromboplastin time. A prognostic model for the estimation of the risk of death within the ensuing 1.5–2 years in patients with non-Hodgkin lymphoma was constructed.ConclusionMarkers of inflammation, anemia, hypercoagulability, dyslipidemia, and poor ECOG status are associated with worse survival in patients with mature B-cell non-Hodgkin lymphoma.

Prognostic value and clinicopathological characteristics of PD-L1 overexpression in non-Hodgkin lymphoma: a meta-analysis

BackgroundProgrammed cell death ligand 1 (PD-L1) has already been detected in various carcinomas. In non-Hodgkin lymphoma (NHL), however, the prognostic value of PD-L1 overexpression remains unclear.MethodsA meta-analysis of 2321 NHL patients from 12 studies was performed. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to evaluate the correlation between PD-L1 overexpression and prognosis of NHL, and odds ratios (ORs) with 95% CIs were used to assess the association of PD-L1 overexpression with clinicopathological factors.ResultsThe results showed that no significant difference between PD-L1 positive and negative groups was detected in NHL (HR: 1.40, 95% CI: 0.90–2.19; P = 0.137). Nevertheless, the results indicated that PD-L1 overexpression was associated with poor prognosis in the subtype of diffuse large B cell lymphoma (DLBCL) (HR: 1.70, 95% CI: 1.05–2.74; P = 0.031). We also performed subgroup analyses and meta-regression. The pooled OR showed that PD-L1 overexpression was associated with B symptoms, higher international prognostic index (IPI) score (3, 4, and 5 points) and Ann Arbor Stages III and IV.ConclusionsThe meta-analysis demonstrated that PD-L1 expression was not associated with prognosis of NHL but was associated with prognosis of DLBCL.

Association between Lactate Dehydrogenase Levels to the Response of Non-Hodgkin Lymphoma in Elderly Patients Who Treated with First-Line Chemotherapy in Sanglah General Hospital.

BACKGROUND:Non-Hodgkin Lymphoma (NHL) is a malignant haematological disease originates in the lymphocytes, caused by an abnormality in lymphocytes development which forms a tumour and may become cancer. Chemotherapy is the main treatment modality for aggressive lymphoma, but only a few patients achieve remission. Several factors such as age, clinical stadium, number of extranodal regions, and Lactate Dehydrogenase (LDH) level played a role in determining response to chemotherapy.AIM:To measure the association between LDH levels to prognosis of NHL in elderly patients who treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy in Sanglah General Hospital.METHODS:This study used a retrospective descriptive study on elderly NHL patients in Sanglah General Hospital from January until December 2014. The evaluation was measured using the IPI score to determine the prognosis of patients. Demographic data, the stadium, extranodal region, LDH level, and response to chemotherapy were recorded.RESULTS:Twenty-five patients were included in the study. The age ranged was between 61-76 years old (Mean 65,68 ± 4,7 years; Median 65 years). The number of male patients was 19 (76%). Diffuse Large B-Cell Lymphoma (DLBCL) is the most common histopathological structure observed on the patients (68%). LDH levels were normal in 51.6% of the patients and considered high in the rests (48.4%). Results of the chemotherapy were a good response in 72.2%. Compared to the patients who showed complete response to chemotherapy, patients with no response (partial response and progression) had significantly higher levels of LDH (OR: 13,1; 95% CI: 1,36-126,30; p = 0,001).CONCLUSION:Non-Hodgkin Lymphoma in elderly patients with no response to chemotherapy had significantly higher levels of LDH than patients with complete response.

Effects of aerobic glycolysis on pathogenesis and drug resistance of non-Hodgkin lymphoma

It has been shown that aerobic glycolysis (AG) plays an important role in the pathogenesis and resistance mechanism of non-Hodgkin lymphoma (NHL) in recent years. Signaling pathway related to abnormal activation of AG can increase the level of AG in lymphatic and hematopoietic cells, while the enzymes related to the activity of AG are involved in the pathogenesis and prognosis of NHL. Drugs that inhibit AG can also inhibit NHL cells in vitro. Drugs inhibiting AG may increase the sensitivity of chemotherapeutic agents and prevent drug resistance. In this article, the role of signaling pathway proteins and regulatory genes related to AG in the pathogenesis and drug resistance of NHL are reviewed, and the AG as a target in the clinical diagnosis and treatment of NHL is discussed.

Hematuria Alone or in Combination with Proteinuria Is a Harbinger of Poor Prognosis in Patients with Non-Hodgkin Lymphoma

Background: Screening for hematuria is essential during health checkups in the general population. However, urine examinations in patients with cancer tend to be overlooked. This study attempted to demonstrate the novel utility of urinalysis in the assessment of the prognosis of non-Hodgkin lymphoma (NHL). Methods: A longitudinal, retrospective cohort study was conducted to examine the association between hematuria and mortality in 294 patients with NHL. Urinalysis was performed using a dipstick test. A multivariate, logistic regression model was constructed to evaluate factors associated with the presence of hematuria. Statistical association between hematuria and the time to all-cause mortality was analyzed using Kaplan-Meier analysis, followed by multivariate proportional hazards regression analysis adjusted for covariates that might be related to mortality. Results: The prevalence of hematuria alone and in combination with proteinuria was 11.6 and 5.1%, respectively. C-reactive protein was a significant factor associated with the presence of hematuria (OR [95% CI] 1.17 [1.03–1.34], p = 0.0194). The cumulative mortality was significantly higher in patients with hematuria alone (51.1%), proteinuria alone (47.1%), and both (66.7%), than in those with neither (24.3%). Moreover, the presence of hematuria alone was significantly associated with all-cause mortality (hazard ratio [95% CI] 1.78 [1.10–3.50], p = 0.0455), and patients with concomitant proteinuria were at the highest risk (4.01 [1.71–8.33], p = 0.0001). Conclusions: In patients with hematuric NHL, systemic inflammation is likely to develop to such a great extent that kidney damage occurs. Therefore, the presence of hematuria, alone or especially in combination with proteinuria, predicts a poor prognosis of NHL.

Recent Progress of Molecular Genetic Characteristics and Prognosis of Non-Hodgkin's Lymphoma--Review

Lymphomas are traditionally divided into Hodgkin's lymphoma and non-Hodgkin's lymphoma(NHL), the NHL is a common hematological cancer, which represents a wide spectrum of illnesses from the most indolent to the most aggressive malignancies, and the detection of related molecular targets will be needed for diagosing each subtype of NHL. Advances in understanding the pathogenesis of NHL have improved the precision of diagnosis and the prognosis evaluation of patients with this disorder, such as chromosomal translocation leading to the up-regulation of oncogene expression. Besides, the deletion of several tumor suppressor genes may cause excessive proliferation in tumor cells, and the single nucleotide polymorphism (SNP) determines the differences of susceptibility, drug-resistance and prognosis of NHL. In addition, DNA methylation, histone modification, non-coding RNA and other epigenetic phenomena play an increasingly important role in the diagnosis, selection of clinical drugs and evaluation of prognosis of NHL. In this review, the recent progress of researches on chromosome translocation, deletion of tumor suppression genes, gene poly-morphism and epigenetics are summarized.

Association of Two Angiogenic Genes Polymorphism with Clinical Course and Prognosis of Non-Hodgkin Lymphoma in Egyptian Patients

Association of Two Angiogenic Genes Polymorphism with Clinical Course and Prognosis of Non-Hodgkin Lymphoma in Egyptian Patients