Incidence Of non-Hodgkin Lymphoma Research Articles

Increased Risk of Non-Hodgkin Lymphoma in Autoimmune Hepatitis: A Large Retrospective Cohort Study.

Background/Objectives: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease caused by an autoimmune attack on hepatocytes. The first-line treatment for AIH comprises two core components: glucocorticoids and thiopurine analog inhibitors and mycophenolate mofetil (MMF). Numerous studies have suggested an increased risk for lymphoma among patients with either rheumatoid arthritis or inflammatory bowel disease (IBD) who are treated with azathioprine/6-mercaptopurine (6-MP). The relative risk of non-Hodgkin lymphoma (NHL) among autoimmune hepatitis patients treated with these immunosuppressive drugs remains unclear. We aimed at investigating the risk of NHL across a large retrospective AIH cohort after a long-term follow-up. Methods: This retrospective, population-based study comprised approximately 2.7 million adults over two decades. It included adult patients aged 20 years or older at the time of autoimmune hepatitis diagnosis who had initiated treatment with azathioprine, 6-MP, or MMF. The primary outcome was the development of non-Hodgkin lymphoma. Results: The study initially included 834 patients diagnosed with AIH. A total of 685 patients remained in the research cohort after matching the data to the local cancer registry. Compared to the predicted NHL rate in the general population, NHL incidence was considerably higher in AIH patients (Standardized Incidence Ratio, SIR = 36.5). Subgroup studies showed that lymphoma mainly affected patients 45 years of age and over and was detected primarily during the first seven years following the AIH diagnosis. No correlation was found between the incidence of NHL and the treatment drug used. Conclusions: Patients with AIH exhibit a markedly higher risk of NHL compared to the general population.

Non-Hodgkin lymphoma incidence, mortality, and survival trends in Brunei Darussalam from 2011 to 2020

BackgroundNon-Hodgkin lymphoma (NHL) has been identified as a significant contributor to the cancer burden. This study investigates the incidence, mortality, and survival trends of NHL cancer in Brunei Darussalam from 2011 to 2020.MethodsThis is a registry-based retrospective study using de-identified data from the Brunei Darussalam Cancer Registry on patients diagnosed with NHL from 2011 to 2020 based on the ICD-10 codes C82-86. Statistical methods include descriptive statistics, age-specific and age-standardised incidence (ASIR) and mortality rates (ASMR), and joinpoint regression for trend analysis. Survival analysis was conducted using Kaplan-Meier plots, log-rank test, and Cox Proportional Hazards regression.ResultsFrom 2011 to 2020, 330 patients were diagnosed with NHL. The majority of patients were males (51.8%) and of Malay descent (82.7%). The age group most diagnosed was 55–74 years (42.3%), with a mean age at diagnosis being 55.1 years. The ASIRs were 12.12 for males and 10.39 per 100,000 for females; ASMRs were 6.11 for males and 4.76 per 100,000 for females. Diffuse large B-cell lymphoma was the most prevalent subtype, accounting for 39.1% of cases. The overall 5-year survival rate was 61.2%, with lower rates observed in older patients and those diagnosed at distant metastasis stage. Furthermore, older age and advanced stage diagnosis significantly increased mortality risk. NHL incidence and mortality rates in Brunei Darussalam remain stable over the period of 10 years, but highlights significant disparities in gender and age.ConclusionsThe findings emphasize the importance of early detection and tailored treatments, especially for high-risk groups, in managing NHL’s burden. These insights underline the need for focused healthcare strategies and continued research to address NHL’s challenges.

The Epidemiological Particularities of Malignant Hemopathies in French Guiana: 2005-2014.

French Guiana is a French Overseas territory with singular features: it has a high prevalence of HIV and HTLV-1, its population is ethnically mixed, with widespread poverty, and up to 20% of the population lives in geographic isolation. In this context, we used registry data to estimate incidence and mortality due to hematological malignancies and to compare them with France and tropical Latin America. ICD codes C90 and C88 were compiled between 2005 and 2014. The direct standardization of age structure was performed using the world population. Survival analysis was performed, and Kaplan-Meier curves were drawn. The overall standardized incidence rate was 32.9 per 100,000 male years and 24.5 per 100,000 female years. Between 2005 and 2009, the standardized incidence rate was 29.6 per 100,000 among men and 23.6 per 100,000 among women, and between 2010 and 2014, it was 35.6 per 100,000 among men and 25.2 per 100,000 among women. Multiple myeloma/plasmocytoma and mature t/NK cell lymphomas, notably adult t-cell lymphoma/leukemia due to HTLV-1 infection, were the two most common hematologic malignancies and causes of death. Non-Hodgkin's lymphoma incidence estimates were greater than global estimates. After adjusting for age, sex, and type of malignancy, people born in a foreign country independently had a poorer case-fatality rate, presumably reflecting difficulties in accessing care. The epidemiology of hematological malignancies in French Guiana has features that distinguish it from mainland France or from Latin America. The incidence of multiple myeloma and adult t-cell lymphoma/leukemia was significantly greater in French Guiana than in France or other Latin American countries.

Incidence and survival of second primary non-Hodgkin lymphoma: A Surveillance, Epidemiology, and End Results-based cohort study.

The aim of this study was to investigate patient survival and factors associated with survival in second primary non-Hodgkin lymphoma (NHL) compared with the first primary NHL. The retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Demographic characteristics, histological types, Ann Arbor stage, and treatment information were collected. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with overall survival (OS) and cancer-specific survival (CSS) in the first and second primary NHLs. Of 318,168 cases followed for 5 years, 299,248 patients developed the first primary NHL and 18,920 patients developed the second primary NHL. This study identified a rising incidence of first and second primary NHL from 2000 to 2014. For the second primary NHL, the OS risk was higher when compared to the first primary NHL (HR: 1.13, 95% CI: 1.11 to 1.15, P <0.001). Risk factors that negatively affected OS in the first primary NHL included being male, over 40 years of age, certain marital statuses, specific histological types, and advanced disease stages. In contrast, being of White race and having histological types such as Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL), and mantle B-cell NHL were associated with better OS outcomes. Treatments like surgery, radiation therapy, and chemotherapy were associated with a lower risk of OS and CSS in the first primary NHL. For the second primary NHL, the detrimental risk factors were similar but also included being over the age of 60. Certain histological types showed a lower OS risk relative to diffuse Large B-cell Lymphoma (DLBCL). While surgery and chemotherapy were beneficial for OS, radiation therapy did not improve survival in second primary NHL cases. Notably, undergoing chemotherapy for the first primary cancer increased the OS risk in the second primary NHL, whereas surgery and radiation seemed to offer a protective effect against OS risk in the second primary NHL (all P <0.05). Our findings emphasize the need for tailored strategies in managing the second primary NHL, given the distinct survival patterns and risk factor profiles compared to the first primary NHL. Future research should aim to further elucidate these differences to improve prognosis and treatment approaches for second primary NHL patients.

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.

CAR-T Cell Therapy Targeted Non-Hodgkin's Lymphoma: Clinical Development and Challenge

Non-Hodgkin's lymphoma incidence has been rising worldwide in last few years. And the dismal prognosis following treatment to cure relapsed or resistant T-cell lymphoma and B-cell malignancies. Today, this therapy has already achieved incredible results with the field of non-Hodgkin's lymphoma. It becomes a new pillar in the treatment of cancer and shows great promise. Recently, there have been a number of new clinical studies and technology discoveries that have led to significant clinical responses to this therapy in certain subpopulations of Non-Hodgkin's Lymphoma. However, there are still many structural and functional challenges that limit the therapeutic efficacy of this therapy. Therefore, new strategies and ideas are needed to overcome the current challenges. The most recent developments and clinical trial findings on this therapy's effectiveness in treating NHL are covered in this review, as well as discussing the limitations of this therapy and the current solutions and strategies to address them.

Estimates of the global burden of non-Hodgkin lymphoma attributable to HIV: a population attributable modeling study

Human immunodeficiency virus (HIV) significantly increases the risk of non-Hodgkin lymphoma (NHL) development, yet the population-level impact on NHL burden is unquantified. We aim to quantify this association and estimate the global burden of HIV-associated NHL. In this meta-analysis, we searched five databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus) from database inception up to September 13, 2023, identifying cohort, case-control, or cross-sectional studies with an effective control group to assess NHL risk among individuals with HIV infection, with two authors extracting summary data from reports. Global and regional HIV-associated population attributable fraction (PAF) and NHL disease burden were calculated based on the pooled risk ratio (RR). HIV prevalence and NHL incidence were obtained from the Joint United Nations Programme on HIV/AIDS (UNAIDS) and Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Trends in NHL incidence due to HIV were assessed using age-standardised incidence rate (ASIR) and estimated annual percentage change (EAPC). This study was registered with PROSPERO (CRD42023404150). Out of 14,929 literature sources, 39 articles met our inclusion criteria. The risk of NHL was significantly increased in the population living with HIV (pooled RR 23.51, 95% CI 17.62-31.37; I2=100%, p<0.0001), without publication bias. Globally, 6.92% (95% CI 2.18%-11.57%) of NHL new cases in 2019 were attributable to HIV infection (30,503, 95% CI 9585-52,209), which marked a more than three-fold increase from 1990 (8340, 95% CI 3346-13,799). The UNAIDS region of Eastern and Southern Africa was the highest affected region, with 44.46% (95% CI 19.62%-58.57%) of NHL new cases attributed to HIV infection. The Eastern Europe and Central Asia region experienced the highest increase in ASIR of NHL due to HIV in the past thirty years, wherein the EAPC was 8.74% (95% CI 7.66%-9.84%), from 2010 to2019. People with HIV infection face a significantly increased risk of NHL. Targeted prevention and control policies are especially crucial for countries in Eastern and Southern Africa, Eastern Europe and Central Asia, to achieve the UNAIDS's '90-90-90' Fast-Track targets. Limited studies across diverse regions and heterogeneity between research have hindered precise estimations for specific periods and regions. Sichuan Provincial People's Hospital, Chengdu, China; Health Care for Cadres of Sichuan Province, Chengdu, China; Science and Technology Department of Sichuan Province, Chengdu, China.

Immunosuppressant Drug-Associated Non-Hodgkin Lymphoma: A Real-World Pharmacovigilance Database Analysis

Background: The association between immunosuppressant drugs and lymphoma has been reported frequently; however, the precise relationship remains uncertain. Non-Hodgkin lymphoma (NHL) is among the most common cancers associated with long-term immunosuppressant drug use. The FDA Adverse Event Reporting System (FAERS) is a publicly available tool that collects reports of adverse events from healthcare professionals, manufacturers and consumers. Methods: Nine immunosuppressant drugs belonging to different classes were shortlisted . The FAERS database was searched for all types of NHL as an adverse event reported between 2013 and 2022. Reporting odds ratio (ROR) was used to measure disproportionality in reporting of adverse events for these drugs. Results: When NHL was analyzed as a percentage of all cancers reported for a particular drug,azathioprine had the highest percentage (22.14%) followed by methotrexate (18.94%), mycophenolate (14.04%), infliximab/biosimilars (11.22%), cyclosporine (10.71%), etanercept (10.44%), tacrolimus (10.13%), adalimumab/biosimilars (8.80%) and sirolimus (8.51%). Drugs with highest ROR for NHL included azathioprine (2.09, 95% CI 1.94-2.24) followed by methotrexate (1.90, 95% CI 1.82-1.98) and azathioprine (1.17, 95% CI 1.10-1.25). Drugs with lowest ROR for NHL included adalimumab/biosimilars (0.62, 95% CI 0.59-0.65) followed by sirolimus (0.66, 95% CI 0.54-0.80) and tacrolimus (0.78, 95% CI 0.73-0.84). Conclusions: Although all immunosuppressive drugs have been associated with an increased risk of developing NHL, it is advisable to exercise caution with prescribing azathioprine, methotrexate and mycophenolate in patients with preexisting risk. While the use of adalimumab is an independent risk factor for the development of lymphoma, it had the lowest odds of NHL compared to other immunosuppressant drugs in the study. Prospective studies are needed to better understand the true incidence of NHL associated with immunosuppressant drugs.

Lower Incidence of Leukemia in Sodium Glucose Cotransporter-2 Inhibitor-Treated Patients with Type 2 Diabetes Mellitus: Result from Large Real-World Cohorts

Objective: Leukemia is the among the top ten most common cancer in the United States of America, with incidence of 14.0 per 100,000 people. While the incidence of non-Hodgkin lymphoma has significantly decreased, the incidence of leukemia has been stable during 2014-2018 [1]. In the meantime, sodium-glucose cotransporter-2 inhibitors (SGLT-2i), a comparatively new class of anti-diabetic medication, has gained significant popularity among clinician due to its cardioprotective and renoprotective properties. Several observational studies and meta-analyses explored the relationship between SGLT-2i and solid tumor, including bladder cancer and breast cancer [2, 3]. Nevertheless, contemporary data for SGLT-2i and leukemia are limited. This large cohort study was aimed to investigate the association between SGLT-2i and the risk of leukemia. Methods: This was a retrospective cohort study including patients with T2DM from 92 hospitals across the United States between 2015 and 2023. Inclusion criteria were patients with T2DM aged 18 years or older who newly initiated treatment with SGLT-2i or DPP-4i. Patients with a history of type 1 diabetes or malignancies were excluded. Propensity score matching was applied to each group to account for confounding factors, including demographic characteristics, comorbidities, laboratory data, and medication history. The primary outcome of interest was the occurrence of incident leukemia, including lymphoid leukemia, myeloid leukemia and monocytic leukemia. Kaplan-Meier analysis and log-rank tests were used to compare the outcomes across the cohorts, while hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using the Cox proportional hazard regression model. Results: A total of 718,276 SGLT-2i initiators were matched to 1,159,112 DPP4i initiators diagnosed with T2DM. Among these, 3,429 incidents of leukemia were identified, with 1,148 occurring in the SGLT2i groups and 2,281 in the DPP-4i group after matching.The baseline characteristics, including ethnicity, comorbidities and medication history, were well-balanced between the two cohorts. SGLT-2i initiators demonstrated a significantly reduced risk of new-onset leukemia compared to those using DPP-4i, including myeloid leukemia (HR, 0.676; 95% CI, 0.589 to 0.776, p &amp;lt; 0.001) and lymphoid leukemia (HR, 0.846; 95% CI, 0.753-0.950, p = 0.005). There was no significant difference in the occurrence of monocytic leukemia (aHR 0.836; 95% CI, 0.556 to 1.257, p = 0.388). Conclusion: This population-based propensity-score matched cohort study showed that SGLT-2i is associated with lower in the risk of developing leukemia when compared to those treated with DPP-4i. These findings highlight the potential therapeutic value of SGLT-2i in the prevention of hematological malignancies in patients with T2DM. Further clinical trials are necessary to explore and validate the potential applications. Reference 1. Cronin, K.A., et al., Annual report to the nation on the status of cancer, part 1: National cancer statistics. Cancer, 2022. 128(24): p. 4251-4284. 2. Garcia, M., et al., SGLT2 Inhibitors and Bladder Cancer: Analysis of Cases Reported in the European Pharmacovigilance Database. J Clin Pharmacol, 2021. 61(2): p. 187-192. 3. Tang, H., et al., SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Diabetologia, 2017. 60(10): p. 1862-1872.

Updated Trends in Incidence and Survival of Mantle Cell Lymphoma from 2000 to 2020

While the incidence of non-Hodgkin's lymphoma (NHL) has declined ~1% per year (Y) since 2015, it is not known if this trend holds true for mantle cell lymphoma (MCL). The Surveillance, Epidemiology and End Results (SEER) 17 database includes MCL data collected from 12 US states between 2000 and 2013. However, since the launch of the new SEER 22 database, there has not yet been a study analyzing MCL trends. SEER 22 added seven more years of follow up (up to 2020) compared to SEER 17 (up to 2013), as well as the states of Illinois, Texas, Idaho, Massachusetts, and New York to the 12 states of SEER 17. Here we provide updated trends in MCL incidence and survival using the SEER 22 database, with subset analysis of age, race, and gender. Age-adjusted incidence (per 100,000 Persons/Y) of reported MCL cases were extracted from SEER 22 and tabulated at 5Y intervals (2000-2019). We found an initial increase in MCL incidence from 0.675 (2000-2004) to 0.789 (2005-2009) to 0.833 (2010-2014), followed by a slight decrease to 0.826 (2015-2019) (Fig. 1A). Using the SEER*Stat platform, we calculated the Annual Percent Change (APC) of MCL incidence from 2000 to 2019. The APC is a standard way to statistically characterize trends in MCL rates over time assuming the rates are to change at a constant percentage of the rate of the previous year. While the MCL APC from 2000 to 2014 was +2.02% signaling an annual increase, that for the years 2015 to 2019 was -0.49% indicating an average 0.49% annual decline in MCL incidence since 2015. This decline was found to be statistically significant when compared the 2000-2014 APC. Unsurprisingly, the incidence of MCL in 2020, the first year of the COVID-19 pandemic, declined to 0.767 compared to 0.814 in 2019, translating into a -5.77% percent change (PC). The PC was calculated as follows: PC=100 x [rate (2020)/rate (2019)-1]. This decrease in MCL rate is less pronounced than the -7.76% PC in NHL incidence in 2020. While these remarkable PCs reflect a drop in reporting and delayed/postponed diagnosis during the first year of the pandemic, the MCL incidence is expected to be less affected considering the aggressive nature of this disease prompting immediate diagnosis and medical care. Notably, the PC in diffuse large B-cell lymphoma (DLBCL) incidence in 2020 compared to 2019 was -3.77%, which contrasts with a larger PC of -8.69% in follicular lymphoma (FL). While DLBCL is aggressive and warrants immediate attention, FL is indolent, and diagnosis tended to be postponed during the early months of the pandemic. Collectively, the observed decrease in MCL incidence in 2020 could potentially reflect a real trend in the continuous MCL decline over time. When we included the 2020 data in the APC analysis, the 2014-2020 APC further decreased to -0.89% compared to -0.49% (2014-2019). The initial increase in MCL incidence (2000-2014) can be explained by improved reporting (access to electronic medical records, MCL being reported as MCL rather than NHL) and improved diagnostic identification of MCL (SOX11, CD5-negative MCL, indolent MCL, adoption of colonoscopy leading to early MCL detection). Following the observed peak in 2014, MCL incidence seems to follow the overall NHL downward trend. Subset analysis of age, gender, and race will be included in the presentation. Overall, we observed no major trends, except for an uptrend in the MCL incidence in the Black population potentially reflecting improved access to healthcare. To compare trends in MCL survival, we analyzed the 5Y observed overall survival (OS). Additionally, we calculated the relative survival rate (RSR) as the ratio of the observed OS divided by the expected OS of an age-matched comparable group from the general population. The 5Y observed OS improved over time: 45.2% (2000-2004), 49.1% (2005-2009), 53.8% (2010-2014), and 57.1% (2015-2019). This translated in a marked improvement in the 5Y RSR reaching 65.5% in 2015-2019. Unfortunately, while the 5Y RSR of the Hispanic population improved over time, it continues to be significantly lower than the non-Hispanic populations, reflecting either a disparity in access to healthcare or an overall worse prognosis. This dramatically contrasts with the 5Y RSR of the Black population, which once was among the lowest (47.3%, 2000-2004), became the highest 72.5%, (2015-2019) reflecting not only a better access to healthcare, but also a shift to a previously unrecognized better overall prognosis of MCL in Black patients (Fig. 1B).

Increasing incidence of non-Hodgkin lymphoma in England, 1985–2019

Abstract Background In the UK, non-Hodgkin lymphoma (NHL) is the most common hematological malignancy and 6th most common cancer overall - accounting for about 14,200 new cases and 4,900 deaths each year. After rising rapidly from the 1980s onwards, the incidence rates of NHL have broadly stabilised in several European and North American countries since the late 1990s. We conducted a retrospective population-based cohort study to examine whether similar changes in the incidence of NHL have also occurred in England from 1985-2019. Methods Individual-level data for patients diagnosed with NHL, and the corresponding national population (denominator) data were obtained from ONS/PHE. Average annual incidence rates (AAIR) were calculated by sex, three age categories (0-34, 35-64 and 65+ years) and seven five-year time periods (1985-89 to 2015-19). Results During the 35-year study period, a total of 304,994 new cases of NHL were registered in England (54% males, 46% females). In young people aged 0-34 years, the AAIRs increased by 33% in males and 60% in females (from 1.8/100,000 in 1985-89 to 2.4/100,000 in 2015-19 in males, and from 1.0/100,000 in 1985-89 to 1.6/100,000 in 2015-19 in females). In middle age (35-64 years), the AAIRs increased by 54% in males and 57% in females (from 13.3 to 20.5 in males, and from 9.6 to 15.1 in females). At older ages (65+ years), the AAIRs increased by 108% in males and 102% in females (from 47.6 to 99.1 in males, and from 34.1 to 68.7 in females). In both sexes and all age categories, the disease was most frequently diagnosed at the advanced Stage 4. With regards to the socioeconomic status, the disease was relatively more commonly diagnosed in the most deprived groups. Conclusions In contrast with many European and North American countries, there has been a steady and substantial increase in the incidence of NHL in England over the past four decades. Overall, the highest increase was observed in males (115%) and those aged 65+ years (109%). Key messages • The reasons behind this continued increase in incidence in England, which is in contrast with most European/North American populations, remain elusive and need further etiological investigation. • Considering that the large majority of cases were diagnosed at the advanced Stage 4, there is an urgent need for clinical guidance to facilitate early diagnosis of NHL.

Differential survival of Brazilian patients with diffuse large B-cell lymphoma with and without HIV infection.

Combinatorial antiretroviral therapy provided improvement of HIV patients' immune function and a decrease in the incidence of non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is one of the most common NHL forms affecting HIV+ patients. The present study aimed to evaluate the impact of HIV infection on the prognosis of patients treated for DLBCL in a reference cancer treatment center in Brazil. A retrospective case-control study was developed with patients followed-up at the Brazilian National Cancer Institute, in which 243 DLBCL patients (91 HIV+ and 152 HIV-) were enrolled. HIV- controls were matched to HIV+ according to date of cancer diagnosis, clinical staging, primary cancer treatment and date of birth. Sociodemographic and cancer treatment data were extracted from medical charts. Kaplan-Meier analyses were carried out to estimate survival, while univariate and multiple Cox regression analyses were used to determine factors associated with mortality. A total of 98 deaths were observed in a 5-year period after cancer diagnosis. A negative association of HIV infection with both overall and disease-specific survival 1 year after cancer diagnosis was observed [hazard ratio (HR) = 1.98 and 1.96, respectively]. The negative association with HIV infection with disease-specific survival remained significant for a 5-year period after cancer diagnosis (HR = 1.53). HIV viral load above 1000 copies/ml at study entry was also associated with shorter overall and cancer-specific survival. HIV infection negatively impacted prognosis and mortality of DLBCL patients irrespective of cancer-related clinical factors.

Association of Obesity and Type 2 Diabetes with Non-Hodgkin Lymphoma: The Multiethnic Cohort.

Given the role of the immune system in non-Hodgkin lymphoma (NHL) etiology, obesity and type 2 diabetes (T2D) may impact NHL development. We examined the association of body mass index (BMI) and T2D with NHL in the multiethnic cohort (MEC). The MEC recruited >215,000 participants in Hawaii and Los Angeles from five racial/ethnic groups; NHL cases were identified through cancer registry linkages. T2D status, and BMI at age 21 and cohort entry were derived from repeated self-reports; for T2D, Medicare claims were also applied. HRs and 95% confidence intervals (CI) for BMI and T2D as predictors of NHL were determined using Cox regression adjusted for relevant covariates. Among 192,424 participants, 3,472 (1.8%) with NHL and 68,850 (36%) with T2D after 19.2±6.6 years follow-up, no significant association between T2D and NHL (HR, 1.04; 95% CI, 0.96-1.13) was observed. Stratification by BMI at cohort entry showed a significant association of T2D with NHL among individuals with normal weight only (HR, 1.18; 95% CI, 1.03-1.37). In a model with both BMI values plus T2D, only overweight (HR, 1.13; 95% CI, 1.01-1.26) and obesity (HR, 1.25; 95% CI, 0.99-1.59) at age 21 were associated with NHL incidence. Stratification by sex, race/ethnicity, and NHL subtype indicated no differences. Our findings suggest an association between T2D and NHL incidence in several subgroups but not in the total population and an elevated risk related to early-life BMI. Excess body weight in early life, rather than T2D, may be a predictor of NHL incidence.

The risk of developing non-Hodgkin lymphoma and the mortality rate in primary Sjögren's syndrome: a single-centre, retrospective cohort study.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that is manifested by the sensation of dry eyes and dry mouth. The higher incidence of non-Hodgkin lymphoma (NHL) among pSS has already been extensively researched. However, there are uncertanties whether the mortality risk in pSS patients and in pSS patients with NHL is increased. The purpose of this study was to describe the prevalence of NHL among pSS patients and to calculate their mortality risk. We retrospectively analysed data on 1367 patients treated in our rheumatology department under the ICD-10 code M35.0. The study finally recruited 155 patients who met the 2016 ACR/EULAR criteria for the diagnosis of pSS. Descriptive statistics was used in data analysis. We applied the indirect standardization by age to compare the incidence rate of NHL in our cohort to general population. Additionally, we compared the mortality in our study to the general population by calculating the standardized mortality ratio (SMR). The overall incidence rate of NHL was 440 per 100,000 patient-years. The SIR compared to the general population was 30.13 (95% CI 12.87-54.63). The overall mortality rate of pSS patients in our cohort was nearly identical to that of the general population (SMR = 0.98 [95% CI (0.47-1.69)]). This study confirms that there are significant differences in lymphoma prevalence, histology, and prognosis across the studied populations. Furthermore, this study found that patients with pSS have similar mortality risk as the general population, and no patient in our cohort died from NHL.

HSA Adductomics Reveals Sex Differences in NHL Incidence and Possible Involvement of Microbial Translocation.

The higher incidence of non-Hodgkin lymphoma (NHL) in males is not well understood. Although reactive oxygen species (ROS) have been implicated as causes of NHL, they cannot be measured directly in archived blood. We performed untargeted adductomics of stable ROS adducts in human serum albumin (HSA) from 67 incident NHL cases and 82 matched controls from the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Regression and classification methods were employed to select features associated with NHL in all subjects and in males and females separately. Sixty seven HSA-adduct features were quantified by liquid chromatography-high-resolution mass spectrometry at Cys34 (n = 55) and Lys525 (n = 12). Three features were selected for association with NHL in all subjects, while seven were selected for males and five for females with minimal overlap. Two selected features were more abundant in cases and seven in controls, suggesting that altered homeostasis of ROS may affect NHL incidence. Heat maps revealed differential clustering of features between sexes, suggesting differences in operative pathways. Adduct clusters dominated by Cys34 oxidation products and disulfides further implicate ROS and redox biology in the etiology of NHL. Sex differences in dietary and alcohol consumption also help to explain the limited overlap of feature selection between sexes. Intriguingly, a disulfide of methanethiol from enteric microbial metabolism was more abundant in male cases, thereby implicating microbial translocation as a potential contributor to NHL in males. Only two of the ROS adducts associated with NHL overlapped between sexes and one adduct implicates microbial translocation as a risk factor.

The epidemiological patterns of non-Hodgkin lymphoma: global estimates of disease burden, risk factors, and temporal trends.

The incidence of non-Hodgkin's lymphoma (NHL) has increased steadily over the past few decades. Elucidating its global burden will facilitate more effective disease management and improve patient outcomes. We explored the disease burden, risk factors, and trends in incidence and mortality in NHL globally. The up-to-date data on age-standardized incidence and mortality rates of NHL were retrieved from the GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD) 2019, focusing on geographic disparities worldwide. We reported incidence and mortality by sex and age, along with corresponding age-standardized rates (ASRs), the average annual percentage change (AAPC), and future burden estimates to 2040. In 2020, there were an estimated 545,000 new cases and 260,000 deaths of NHL globally. In addition, NHL resulted in 8,650,352 age-standardized DALYs in 2019 worldwide. The age-specific incidence rates varied drastically across world areas, at least 10-fold in both sexes, with the most pronounced increase trend found in Australia and New Zealand. By contrast, North African countries faced a more significant mortality burden (ASR, 3.7 per 100,000) than highly developed countries. In the past decades, the pace of increase in incidence and mortality accelerated, with the highest AAPC of 4.9 (95%CI: 3.6-6.2) and 6.8 (95%CI: 4.3-9.2) in the elderly population, respectively. Considering risk factors, obesity was positively correlated with age-standardized incidence rates (P< 0.001). And North America was the high-risk region for DALYs due to the high body mass index in 2019. Regarding demographic change, NHL incident cases are projected to rise to approximately 778,000 by 2040. In this pooled analysis, we provided evidence for the growing incidence trends in NHL, particularly among women, older adults, obese populations, and HIV-infected people. And the marked increase in the older population is still a public health issue that requires more attention. Future efforts should be directed at cultivating health awareness and formulating effective and locally tailored cancer prevention strategies, especially in most developing countries.

Hepatitis Virus-associated Non-hodgkin Lymphoma: Pathogenesis and Treatment Strategies.

Over the last decade, epidemiological studies have discovered a link between hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL). The regression of HCV-associated NHL after HCV eradication is the most compelling proof supporting HCV infection's role in lymphoproliferative diseases. HBV infection was found to significantly enhance the incidence of NHL, according to the epidemiological data. The exact mechanism of HCV leading to NHL has not been fully clarified, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HCV and cytokines; (2) Direct mechanisms: oncogenic effects mediated by intracellular HCV proteins; (3) hit-and-run mechanism: permanent genetic B lymphocytes damage by the transitional entry of HCV. The specific role of HBV in the occurrence of NHL is still unclear, and the research on its mechanism is less extensively explored than HCV, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HBV; (2) Direct mechanisms: oncogenic effects mediated by intracellular HBV DNA. In fact, it is reasonable to consider direct-acting antivirals (DAAs) as first-line therapy for indolent HCV-associated B-NHL patients who do not require immediate chemotherapy. Chemotherapy for NHL is affected by HBV infection and replication. At the same time, chemotherapy can also activate HBV replication. Following recent guidelines, all patients with HBsAg positive/HBV DNA≥2,000 IU/mL should be treated for HBV. The data on epidemiology, interventional studies, and molecular mechanisms of HCV and HBV-associated B-NHL are systematically summarized in this review.

Treated chronic hepatitis B is a good prognostic factor of diffuse large B-cell lymphoma.

Chronic hepatitis B (CHB) is a risk factor for non-Hodgkin lymphoma (NHL). Our recent study suggested that antiviral treatment may reduce the incidence of NHL in CHB patients. This study compared the prognoses of hepatitis B virus (HBV)-associated diffuse large B-cell lymphoma (DLBCL) patients receiving antiviral treatment and HBV-unassociated DLBCL patients. This study comprised 928 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at two referral centers in Korea. All patients with CHB received antiviral treatment. Time-to-progression (TTP) and overall survival (OS) were the primary and secondary endpoints, respectively. Among the 928 patients in this study, 82 were hepatitis B surface antigen (HBsAg)-positive (the CHB group) and 846 were HBsAg-negative (the non-CHB group). The median follow-up time was 50.5 months (interquartile range [IQR]=25.6-69.7 months). Multivariable analyses showed longer TTP in the CHB group than the non-CHB group both before inverse probability of treatment weighting (IPTW; adjusted hazard ratio [aHR]=0.49, 95% confidence interval [CI]=0.29-0.82, p=0.007) and after IPTW (aHR=0.42, 95% CI=0.26-0.70, p<0.001). The CHB group also had a longer OS than the non-CHB group both before IPTW (HR=0.55, 95% CI=0.33-0.92, log-rank p=0.02) and after IPTW (HR=0.53, 95% CI=0.32-0.99, log-rank p=0.02). Although liver-related deaths did not occur in the non-CHB group, two deaths occurred in the CHB group due to hepatocellular carcinoma and acute liver failure, respectively. Our findings indicate that HBV-associated DLBCL patients receiving antiviral treatment have significantly longer TTP and OS after R-CHOP treatment than HBV-unassociated DLBCL patients.

Occupational Exposures and Risks of Non-Hodgkin Lymphoma: A Meta-Analysis.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group with different types of diseases. It remains unclear as to what has led to an increase in incidences of NHL, however, chemical substance exposure is known to be one of the risk factors for the disease. Therefore, we performed a systematic review and meta-analysis including case-control, cohort, and cross-sectional observational epidemiological studies to verify the association between occupational exposure to carcinogens and NHL risk. Articles between the years 2000 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI web app. Post-completion, the selected articles were extracted and analyzed via the RedCap platform. Our review resulted in 2719 articles, of which 51 were included in the meta-analysis, resulting in an overall OR of 1.27 (95% CI 1.04-1.55). Furthermore, it was observed that the main occupation associated with the increased risk of NHL was that in which workers are exposed to pesticides. We therefore conclude that the evidence synthesis of the epidemiological literature supports an increased risk for NHL, regardless of subtype, considering occupational exposure to certain chemical compounds, mainly pesticides, benzene, and trichlorethylene, and certain classes of work, primarily in the field of agriculture.

Abstract 6497: Availability of healthcare providers and its association with survival outcomes in non-Hodgkin lymphoma in the United States

Abstract Background: Survival outcome in Non-Hodgkin lymphoma (NHL) is significantly better in earlier stages, compared to advanced stages. Early identification of signs and symptoms, and prompt specialist availability and referral, are crucial for diagnosis and treatment at earlier stages. Mounting physician shortages are a growing concern, and we sought to analyze their effect on NHL mortality rates. Methods: We extracted data on the age-adjusted mortality rate (AAMR) and crude incidence rate (CIR) of NHL for all U.S. states and the District of Columbia from the Center for Disease Control (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database (2017-2019). Nevada was excluded due to missing information. Data on the state-wise number of primary care physicians (PCPs) was obtained from the Association of American Medical Colleges (AAMC) state physician workforce data report (2020), and of Hematology/Oncology specialists (HOs) was gathered from the National Provider Identifier (NPI) registry (2020). The number of PCPs and HOs per each NHL incidence (PCP/CIR, HO/CIR respectively) was then calculated. Correlations were analyzed using Pearson’s coefficient. Statistical analysis was performed using VassarStats. Results: Median AAMR for NHL in the US was 5.15 (IQR 4.35, 5.95) per 100, 000 population. The median number of PCP and HO per each case of NHL incidence was 4.32 (IQR 3.43, 5.21), and 0.28 (IQR 0.1, 0.37) respectively. States with fewer PCPs per each NHL incidence had higher AAMR (r=-0.37, p=0.007). States with a lower number of HOs per each NHL incidence had higher AAMR (r=-0.41, p=0.003) Conclusions: Based on the analysis, the availability of a lower number of PCPs and HOs per each NHL incidence is associated with increased AAMR of the disease. This data may strengthen the need for intensification of focus on decreasing the soaring physician shortages in the states, in order to help decrease the overall mortality associated with NHL. Citation Format: Shiva Jashwanth Gaddam, Udhayvir Singh Grewal, Zara Hassan, Poornima Ramadas. Availability of healthcare providers and its association with survival outcomes in non-Hodgkin lymphoma in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6497.