New insights into the epidemiology of non-Hodgkin lymphoma and implications for therapy.
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ABSTRACT:
SUBMITTER: Chihara D
PROVIDER: S-EPMC4698971 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
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New insights into the epidemiology of non-Hodgkin lymphoma and implications for therapy.
Chihara Dai D Nastoupil Loretta J LJ Williams Jessica N JN Lee Paul P Koff Jean L JL Flowers Christopher R CR
Expert review of anticancer therapy 20150411 5
Non-Hodgkin lymphoma (NHL) comprises numerous biologically and clinically heterogeneous subtypes, with limited data examining the risk factors for these distinct disease entities. Many limitations exist when studying lymphoma epidemiology; therefore, until recently, little was known regarding the etiology of NHL subtypes. This review highlights the results of recent pooled analyses examining the risk factors for NHL subtypes. We outline the heterogeneity and commonality among the risk factors fo ...[more]
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Project description:There has been a recent emergence of novel targeted agents for treatment of Hodgkin and non-Hodgkin lymphoma. In particular, antibodies and antibody-drug conjugates directed against surface antigens, agents that block immune checkpoint pathways, and small molecule inhibitors directed against cell signaling pathways have shown significant promise in patients with relapsed and refractory disease and in the frontline setting. With the development of these new therapies, cytotoxic chemotherapy may be avoided entirely in some clinical settings. This review will present the latest information on these novel treatments in Hodgkin and non-Hodgkin lymphoma and will discuss both recently approved agents as well as drugs currently being studied in clinical trials.
| S-EPMC4588185 | biostudies-literature
Project description:BackgroundNon-Hodgkin lymphoma (NHL), the most common hematologic malignancy, consists of numerous subtypes. The etiology of NHL is incompletely understood, and increasing evidence suggests that risk factors may vary by NHL subtype. However, small numbers of cases have made investigation of subtype-specific risks challenging. The International Lymphoma Epidemiology Consortium therefore undertook the NHL Subtypes Project, an international collaborative effort to investigate the etiologies of NHL subtypes. This article describes in detail the project rationale and design.MethodsWe pooled individual-level data from 20 case-control studies (17471 NHL cases, 23096 controls) from North America, Europe, and Australia. Centralized data harmonization and analysis ensured standardized definitions and approaches, with rigorous quality control.ResultsThe pooled study population included 11 specified NHL subtypes with more than 100 cases: diffuse large B-cell lymphoma (N = 4667), follicular lymphoma (N = 3530), chronic lymphocytic leukemia/small lymphocytic lymphoma (N = 2440), marginal zone lymphoma (N = 1052), peripheral T-cell lymphoma (N = 584), mantle cell lymphoma (N = 557), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (N = 374), mycosis fungoides/Sézary syndrome (N = 324), Burkitt/Burkitt-like lymphoma/leukemia (N = 295), hairy cell leukemia (N = 154), and acute lymphoblastic leukemia/lymphoma (N = 152). Associations with medical history, family history, lifestyle factors, and occupation for each of these 11 subtypes are presented in separate articles in this issue, with a final article quantitatively comparing risk factor patterns among subtypes.ConclusionsThe International Lymphoma Epidemiology Consortium NHL Subtypes Project provides the largest and most comprehensive investigation of potential risk factors for a broad range of common and rare NHL subtypes to date. The analyses contribute to our understanding of the multifactorial nature of NHL subtype etiologies, motivate hypothesis-driven prospective investigations, provide clues for prevention, and exemplify the benefits of international consortial collaboration in cancer epidemiology.
| S-EPMC4155460 | biostudies-literature
Project description:Our studies identify the role of mIR-28 in germinal center response and its therapeutic potential for the treatment of non-Hodgkin lymphomas
2017-05-03 | GSE81236 | GEO
Project description:Proton therapy (PT) is a highly conformal type of radiation therapy that can target the tumor while sparing dose to surrounding normal tissues. This study reviews a single institution's experience managing patients with non-Hodgkin lymphoma (NHL) treated with PT. Eleven patients with NHL were treated with PT from January 2008 to January 2014 on an institutional review board-approved outcomes tracking protocol, and included patients with indolent orbital lymphoma (n = 4), primary mediastinal B-cell lymphoma (n = 3), plasmablastic lymphoma (n = 2) and natural killer (NK) T-cell lymphoma (n = 2). The median follow-up was 38 months. The 2-year rate of local control was 91%, with one patient with NK T-cell lymphoma having recurrence in-field. Toxicities were limited to grade 2 at highest, during follow-up. PT is a feasible and effective treatment for NHL. Early outcomes are favorable. Longer follow-up and more patients are needed to confirm our findings.
| S-EPMC4732409 | biostudies-literature
Project description:Non-Hodgkin Lymphoma (NHL) is the most common hematologic malignancy. More than 20,000 people in United States, more than 37,000 people in Europe and more than 199,000 people worldwide die of NHL every year. Recent advances in immunotherapeutic approaches for cancer have resulted in development of new classes of very effective immunotherapeutic approaches including chimeric antigen receptor T (CAR-T) cell therapy that are designed to bypass cancer immune evasion. Here, we review recent advances in CAR-T cell therapy for NHL. US food and drug administration (FDA) recently approved axicabtagene ciloleucel (Yescarta) a CD19 CAR T cell therapy for treatment of relapsed refractory diffuse large B cell lymphoma (DLBCL), high grade lymphoma, and primary mediastinal B cell lymphoma (PMBCL). Approval of Yescarta and rapid development of other CAR T cell therapies at various stages of development are opening up the door for a new wave of CAR T cell therapies that will dramatically change the way we treat NHL and hopefully other malignancies in the near future.
| S-EPMC5990429 | biostudies-literature
Project description:Exportin-1 (XPO1) is a key player in the nuclear export pathway and is overexpressed in almost all cancers. This is especially relevant for non-Hodgkin lymphoma (NHL), where high XPO1 expression is associated with poor prognosis due to its oncogenic role in exporting proteins and RNA that are involved in cancer progression and treatment resistance. Here, we discuss the proteins and RNA transcripts that have been identified as XPO1 cargo in NHL lymphoma including tumour suppressors, immune modulators, and transcription factors, and their implications for oncogenesis. We then highlight the research to date on XPO1 inhibitors such as selinexor and other selective inhibitors of nuclear export (SINEs), which are used to treat some cases of non-Hodgkin lymphoma. In vitro, in vivo, and clinical studies investigating the anti-cancer effects of SINEs from bench to bedside, both as a single agent and in combination, are also reported. Finally, we discuss the limitations of the current research landscape and future directions to better understand and improve the clinical utility of SINE compounds in NHL.
| S-EPMC9855521 | biostudies-literature
Project description:ImportanceThe management of lymphoma diagnosed during pregnancy is controversial and has been guided largely by findings from case reports and small series.ObjectiveTo determine maternal and fetal outcomes of women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy.Design, setting, and participantsThis retrospective analysis studied a cohort of 39 pregnant women diagnosed with HL and NHL (31 HL and 8 NHL) at a single specialized cancer institution between January 1991 and December 2014.Main outcomes and measuresWe examined data on disease and treatment characteristics, as well as maternal and fetal complications and outcomes. The Kaplan-Meier method was used to compare progression free survival (PFS) and overall survival (OS) according to receipt of antenatal therapy and other clinical factors. Univariate and multivariate analyses were performed by using Cox proportional hazard regression models to identify potential associations between clinical and treatment factors and survival.ResultsThe median (range) age of the 39 women in the patient cohort was 28 (19-38) years; 32 women (82%) had stage I or II disease at diagnosis, and 13 had bulky disease. Three women electively terminated the pregnancy to allow immediate systemic therapy; of the remaining 36 women, 24 received antenatal therapy (doxorubicin based combination chemotherapy in 20 of 24 patients), and 12 deferred therapy until after delivery. Four women experienced miscarriage, all of whom had received antenatal systemic therapy and 2 during the first trimester. Delivery occurred at a median (range) of 37 (32-42) weeks and was no different based on receipt of antenatal (median [range], 37 [33-42] weeks) vs postnatal (median [range], 37 [32-42] weeks) therapy (P = .21). No gross fetal malformations or anomalies were detected. At a median (range) follow-up time of 67.9 (8.8-277.5) months since the diagnosis of lymphoma, 5-year rates of PFS and OS were 74.7% and 82.4%, respectively; these rates did not differ according to timing of therapy. On univariate analysis, bulky disease (>10 cm), extranodal nonbone marrow involvement, and poor performance status (Eastern Cooperative Oncology Group score, ≥2) predicted increased risk of disease progression. On multivariate analysis, extranodal nonbone marrow disease and performance status remained significant for both PFS and OS.Conclusions and relevanceSystemic therapy given for lymphoma after the first trimester of pregnancy is likely safe and results in acceptable maternal and fetal outcomes.
| S-EPMC7457973 | biostudies-literature
Project description:BackgroundNon-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.MethodsWe pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE).ResultsRisks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10(-4)), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10(-4)). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.ConclusionsUsing a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.
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Project description:Classical Hodgkin lymphoma (cHL) is characterized by nearly universal genetic alterations in 9p24.1, resulting in constitutive expression of PD-1 ligands. This likely underlies the unique sensitivity of cHL to PD-1 blockade, with response rates of ?70% in relapsed/refractory disease. There are now numerous clinical trials testing PD-1 inhibitors in earlier stages of treatment and in combination with many other therapies. In general, non-Hodgkin lymphomas (NHLs) do not display a high frequency of 9p24.1 alterations and do not share cHL's vulnerability to PD-1 blockade. However, a few entities have genetic or immunologic features that may predict sensitivity to immune checkpoint blockade. These include primary mediastinal B cell lymphoma, primary central nervous system lymphoma, and primary testicular lymphoma, which harbor frequent alterations in 9p24.1, as well as Epstein Barr virus (EBV)-infected lymphomas, where EBV infection leads to increased PD-L1 expression. Although these subtypes may be specifically vulnerable to PD-1 blockade, the majority of NHLs appear to be minimally sensitive to PD-1 blockade monotherapy. Current investigations in NHL are therefore focusing on targeting other checkpoints or studying PD-1-based combination therapy. Looking forward, additional insight into the most common mechanisms of resistance to immune checkpoint inhibitors will be important to guide rational clinical trial design. In this review, we describe the biological basis for checkpoint blockade in cHL and NHL and summarize the clinical data generated to date. Guided by our rapidly evolving understanding of the pathobiology of various lymphoma subtypes, we are hopeful that the role of checkpoint inhibitors in lymphoma treatment will continue to grow.
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Project description:Background Gastrointestinal tract is the most common site of extranodal non-Hodgkin lymphoma (EN-NHL). Most of the published data have been on gastric NHL with limited studies on primary intestinal non-Hodgkin lymphoma (PI-NHL) considering rare incidence. We performed epidemiological and survival analysis for PI-NHL from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Methods A total of 9,143 PI-NHL cases of age ≥ 18 years were identified from the SEER 18 database for the period 2000 - 2015. Totally, 8,568 patients were included for survival analysis. Cause-specific survival (CSS) and overall survival (OS) analysis were done for PI-NHL and PI-diffuse large B-cell lymphoma (PI-DLBCL) using sex, age of onset, treatment, histology, stage, and year of diagnosis. Survival analysis was done by using Cox proportional hazard model and Kaplan-Meier plot with log-rank test. Results The percentage of PI-NHL of all the intestinal cancers and EN-NHL were 1.35%, and 10.52%, respectively. The age-adjusted incidence was 0.9145/100,000 population for the study population. PI-NHL was more common among patients aged ≥ 60 years, male and non-Hispanics Whites. Majority of patients were diagnosed at stage 1 and 2 (74%), and DLBCL (44.8%) was the most common histology. Overall median survival was 111 (95% confidence interval (CI): 105 - 117) months. In OS analysis, significant increased risk of mortality was seen with T-cell NHLs vs. DLBCL (hazard ratio (HR): 2.56), patients aged ≥ 60 vs. < 60 years (HR: 2.87), stage 4 vs. stage 1 (HR: 1.93), male vs. female (HR: 1.17), with best outcome seen in patient treated with combination of chemotherapy and surgery vs. none (HR: 0.45). Similar results were seen in CSS and for PI-DLBCL as well. Significant improvement in outcomes was observed for PI-DLBCL patients receiving chemotherapy with/without surgery. Conclusions Findings from our large, population-based study reveal PI-NHL is a rare type of intestinal malignancy with significant difference in survival based on histological and epidemiological characteristics.
| S-EPMC9451569 | biostudies-literature