Incidence Of Chronic Lymphocytic Leukemia Research Articles

A Study on Geographic Correlation between Indoor Radon Exposure and Leukemia Incidence in Canada.

In Canada, leukemia is diagnosed at a rate of 15 cases per 100,000 persons and accounts for about 3% of all new primary cancers. In this study, geographical correlation between residential radon exposure and leukemia incidence was investigated at a provincial level with more accurate long-term radon measurement data in 21,330 homes and 10-y (2000-2009) age standardized incidence rates per 100,000 population for various subtypes of leukemia. The analyses showed that the incidence rate of non-Hodgkin lymphoma is statistically significantly correlated with average indoor radon (222Rn) concentration for Canadian females (p = 0.01210) but not for males. At a provincial level, the association between average indoor radon level and chronic lymphocytic leukemia incidence rate is statistically significant (p = 0.0167), and the correlation is somewhat stronger for females (p = 0.0043). No correlation was found between indoor radon exposure and any other subtypes of leukemia evaluated in this study.

Increased Environmental Temperature Is an Emerging Health Risk That Correlates with Rates of Acute Lymphoblastic Leukemia in Europe

Background: The World Meteorological Organization (WMO) has calculated that European temperatures have increased at more than double the global average over the last 30 years 1. Besides research in radiation, little research has focused on how this might connect to the mechanisms initiating mutations in ALL. Both latitude and solar irradiance are potential risk factors in the development of ALL 2,3. Latitude covaries with the intensity of solar irradiance and ambient temperature, and both could therefore influence the risk of ALL. Furthermore, high ambient temperature during pregnancy was found to be associated with increased likelihood of childhood ALL 4. Global increases in temperature escalate the likelihood of extreme heat events, which in mammals increases reactive oxygen species, increases DNA damage, and suppresses the immune system 5. Few studies have evaluated changes in ambient temperature as a risk factor for ALL in Europe. We also included chronic lymphocytic leukemia (CLL) for comparison. Objective:To investigate the relationship between population-weighted country centroids (location of greatest population density), average country yearly temperature, solar irradiance and ALL and CLL rates in 40 European countries between the years 2010 and 2019. Design/Method:Incidence and prevalence rates for ALL and CLL (Age-standardized data with males and females) were obtained from the Global Health Data Exchange (GHDx) database. Population-weighted latitude/longitude centroids for Europe 6 were obtained from Baylor University and input into the Global Solar Atlas to obtain the average yearly global horizontal irradiance values. European temperature data was obtained from the Climatic Research Unit at the University of East Anglia (Copernicus Climate Data Store) 7. ALL and CLL incidence and prevalence rates per 100,000 people for 40 European countries were compared by linear regression to each country's temperature or solar irradiance at the population centroids. Statistical analyses were performed using GraphPad Prism and Excel. Results:After2010, we detected a significant positive correlation between ALL incidence and prevalence rates with mean annual temperature across countries for each year of analysis (for example in 2014 the ALL prevalence p-value = 0.01 and R= 0.4, see Figure 1). There was also an increase in the significance of this relationship over time between 2010 and 2019 (Figure 1B). We also detected a significant positive correlation between the increase in mean annual temperature across Europe and an increase in ALL over the past decade (Figure 1B). However, no relationship was established in this study for solar irradiance or population-weighted latitude and CLL prevalence and incidence rates. Conclusions:Increasing mean annual temperatures may increase the risk of developing ALL. We speculate this may be connected through increases in extreme weather events impacting oxidative stress, DNA damage, and/or suppression of the immune system. Considering the global climate crisis, the WMO finding of higher European temperature increases and our finding of significance between temperature and ALL rates, these relationships should be functionally studied. Finally, these studies should be expanded to countries outside of Europe. References 1 World Meteorological Organization. Temperatures in Europe increase more than twice global average. (2022). 2 Pordanjani, S. R., Kavousi, A., Mirbagheri, B., Shahsavani, A. & Etemad, K. Temporal trend and spatial distribution of ALL in Iranian children during 2006-2014: a mixed ecological study. Epidemiol. Health42, (2020). 3 Coste, A. et al. Residential exposure to UV light and risk of precursor B-cell ALL: assessing the role of individual risk factors, the ESCALE and ESTELLE studies. Cancer Causes Control28, 1075-1083 (2017). 4 Rogne, T. et al. High Ambient Temperature in Pregnancy and Risk of Childhood ALL. medRxiv (2023) 5 Chauhan, S. S., Rashamol, V. P., Bagath, M., Sejian, V. & Dunshea, F. R. Impacts of heat stress on immune responses and oxidative stress in farm animals and nutritional strategies for amelioration. Int. J. Biometeorol.65, 1231-1244 (2021). 6 Hamerly, G. Population-weighted European state centers. (2006). 7 Climatic Research Unit, U. of E. A. Temperature and precipitation gridded data for global and regional domains derived from in-situ and satellite observations. (2023).

Global miRNA profiling reveals key molecules that contribute to different chronic lymphocytic leukemia incidences in Asian and Western populations.

It has been known for decades that the incidence of chronic lymphocytic leukemia (CLL) is significantly lower in Asia than in Western countries, but the reason responsible for this difference still remains a major knowledge gap. Using GeneChip® miRNA array to analyze the global microRNA expression in B lymphocytes from Asian and Western CLL patients and healthy individuals, we have identified microRNA with CLL-promoting or suppressive functions that are differentially expressed in Asian and Western individuals. In particular, miR-4485 is upregulated in CLL patients of both ethnic groups, and its expression is significantly lower in Asian healthy individuals. Genetic silencing of miR-4485 in CLL cells suppresses leukemia cell growth, whereas ectopic expression of miR-4485 promotes cell proliferation. Mechanistically, miR-4485 exerts its CLL-promoting activity by inhibiting the expression of TGR5 and activating the ERK1/2 pathway. In contrast, miR-138, miR-181a, miR- 181c, miR-181d, and miR-363 with tumor-suppressive function are highly expressed in Asian healthy individuals. Our study suggests that differential expression of several important microRNA with pro- or anti-CLL functions in Asian and Western B lymphocytes likely contributes to the difference in CLL incidence between the two ethnic groups, and that miR-4485 and its downstream molecule TGR5 could be potential therapeutic targets.

Trends of chronic lymphocytic leukemia incidence and mortality in the United States: a population-based study over the last four decades

ABSTRACT Background Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults, and its incidence is higher in elderly individuals. This study aims to examine the burden of CLL in the United States (US) by exploring the incidence-based rates (IBR) and incidence-based mortality (IBMR) across four decades. Research design and methods CLL incidence data were obtained from the SEER-8 registry, covering 8.3% of the US population. Cases were identified using specific diagnostic codes and excluded if diagnosed on autopsy or death certificate. Age-standardized IBR and IBMR were calculated based on age, sex, and ethnicity/race. Joinpoint Regression Program was used to analyze changing trends in incidence and mortality. Results Since 2011, males’ and females’ IBRs declined by −1.72%/year (p = 0.028) and −1.07%/year (p = 0.222), respectively. IBR of patients > 75 years increased by 4.01%/year (p < 0.001) form 1998–2010, then declined by 2.02%/year (p = 0.011). IBR of Blacks increased by 0.96%/year (p < 0.001) throughout the study period. CLL IBMR stabilized at −0.38%/year (p = 0.457) since 2012. Whites’ IBMR plateaued at a rate of −0.10%/year (p = 0.857) form 2012–2019, while blacks’ IBMR increased by 1.40%/year (p = 0.056) between 2000–2019. Conclusions The analysis revealed a decline in CLL incidence since 2013, with stable mortality rates since 2012, indicating advancements in CLL management.

Distinct Immunogenetic Profiles of Chronic Lymphocytic Leukemia in Asia: A Taiwan Cooperative Oncology Group Registry Study

Asian patientswith chronic lymphocytic leukemia (CLL) exhibit immunoglobulin heavy variable (IGHV) gene repertoires that are distinct from those observed in Western populations, and a higher proportion of Asian CLL patients carry heavy loads of somatic hypermutations (SHM) within the B-cell receptor immunoglobulins (BcR IG). Due to the low regional incidence of CLL in Asia, only a limited number of studies had attempted to probe the phenomenon of BcR IG stereotypy in Asian populations. In this study, we analyzed the IGHV-IGHD-IGHJ gene rearrangements from a series of 255 CLL patients recruited in a nationwide, multicenter study in Taiwan. Our analysis revealed that the IGHV gene repertoire was characterized by evident biases, with IGHV3-7, IGHV4-34, and IGHV3-23 being the most frequent rearranged IGHV genes, and a higher proportion of cases carrying mutated IGHV. In terms of BcR stereotypy, the incidence of major subsets was less frequent in this cohort, with subsets #77 and #28A being the most common, while the incidence of minor subsets was approximately equivalent to that reported in the Western cohorts. With this study, we provide evidence that CLL in Asia is indeed associated with distinct immunogenetic characteristics regarding IGHV gene usage, SHM status, and BcR IG stereotypy.

Shift in First-Line Therapies for United States Veterans Health Administration (VHA) Patients with Chronic Lymphocytic Leukemia (CLL) from 2014 to 2021

Introduction: The emergence of novel agents (NAs) in chronic lymphocytic leukemia (CLL) management marks a move away from a chemotherapy-based paradigm in less than a decade. This has resulted in better treatment tolerance and improved overall survival. The Veteran Health Administration (VHA) offers an attractive population for examining CLL treatments patterns because of two main reasons. It serves mainly older white male population, where incidence of CLL is higher, and is the only single payer national health program that provides equal access to medications. This aim of the study is to assess large population-based uptake of the NAs and to analyze the trends in chemotherapy-based regimen replacement by NA in front-line (1L) CLL. Methods: This is a retrospective study of structured EMR data for adult patients with ICD9 and ICD10 CLL codes within the VHA who initiated 1L treatment with one of 14 CLL treatment [eight NAs and six chemotherapy-based regimens] from 1/1/2014 to 12/31/2021. Data were extracted from the VHA electronic health record. Patients came from all 18 Veterans Integrated Service Networks, spanning all 50 states and US territories. Descriptive statistics were used to summarize baseline characteristics and treatments by calendar year. Results: A cohort of 4,473 patients were identified who received at least one 1L CLL therapy of interest. The median age was 69 years and 98% were male. The proportion of patients who received an NA as 1L treatment for CLL increased from 2014 to 2021, with a corresponding decrease in chemotherapy-based regimens (Figure 1). In 2017, the proportion of NAs surpassed chemotherapy-based regimen use (52 vs 48%, respectively). This gap continued to widen throughout the study period, with the use of chemotherapy-based regimens plateauing for the last three fiscal years of the study period at ~20%. The use of ibrutinib (90%) accounted for the greatest proportion of 1L NA use over the study period, followed by venetoclax (5%), acalabrutinib (4%), and idelalisib (1%). Until 2018, ibrutinib made up nearly 100% of the NA use with a steady decline thereafter reaching 62% in 2021. The proportion of patients on 1L venetoclax increased annually from 2018 (2%) to 2021 (19%). Similarly, the proportion of patients on 1L acalabrutinib increased annually from 2019 (0%) to 2021 (19%). The proportion of patients on 1L idelalisib increased early in 2015 (4%) but declined throughout the remaining study period (0-1%) (Figure 2). Conclusions: This is one of the largest studies that provides important epidemiological data regarding emerging 1L treatment patterns among VHA patients with CLL. There has been a major shift in 1L treatments with NAs outpacing chemotherapy-based regimens from 2017-2021. Within NAs, there is an ongoing transition from first generation Bruton Tyrosine Kinase (BTK) inhibitor to fixed duration treatments and second generations BTK inhibitors with better side effect profiles. The trend shift will continue to evolve as multiple NAs combinations that offer deeper response and limited/guided treatment duration enter the treatment landscape. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Trends of Chronic Lymphocytic Leukemia Incidence and Mortality in the United States: A Population-Based Study over the Last Four Decades

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults, with more than 90% of newly diagnosed cases occurring in patients more than 64 years of age. It is to be noted that multiple studies reported improved survival over the past 4 decades which is attributed to advancement in treatment and understanding of the disease. However, to better examine the burden of CLL in the United States (US) we investigated the incidence and incidence-based mortality rates in the US over the past 4 decades using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: SEER-8 registry, 8.3% of the US population, was used to study CLL/SLL cases from 1978-2019. Incidence-based (IBR) and incidence-based mortality (IBMR) rates were calculated by sex, age, and ethnicity/race. Patients were divided into four categories according to age of diagnosis, wherein <55 (young-onset CLL), 55-64, 65-74 and >75 years of age. Annual percent change was then calculated using joinpoint regression software. The best model with the least number of joinpoints was then selected. Results: Over the study period, CLL IBR increased by 0.75% (p=0.202). The overall IBR steadily increased from 1978 until 2013 before declining at a rate of -2.05%/year (p=0.031). Males’ IBR plateaued until 1998 followed by an increase of 2.80%/year (p<0.001) until 2011 only to then decline by -1.72%/year (p=0.028). Similarly, females’ IBR had insignificant fluctuations from 1978-2002 followed by an increase of 2.44%/year (p<0.001) until 2011 and an insignificant decline from 2011-2019 (APC=-1.07%/year, p=0.222). Among patients with young-onset CLL, IBR increased by 0.57%/year (p=0.034) up to 2008 and by 11.89%/year (p=0.521) from 2008-2011, followed by a decline of -1.39%/year (p=0.465). Likewise, patients >75 years of age's IBR declined by 0.52%/year (p=0.028) till 1998, increased by 4.01%/year (p<0.001) to 2010, and then declined by 2.02%/year (p=0.011). After years of increasing rates among Whites', IBR declined among Whites beginning in 2013 (APC=-2.12%/year; p=0.037). In contrast, Blacks’ rates increased by 0.96%/year (p<0.001) throughout the study period. (Figure) Over the study period, CLL IBMR was 2.10%/year (p<0.001). The overall CLL IBMR steadily increased from 1978 till 2012 and stabilized at -0.38%/year (p=0.457) until 2019. Males’ IBMR increased by 26.61%/year (p<0.001) during 1978-1980, then increased at a slower rate of 2.97%/year (p<0.001) and 0.46%/year (p<0.001) between 1980-1989 and 1989-2019, respectively. Similarly, females’ rates increased by 11.91%/year (p<0.001) between 1978-1984, and by 0.52%/year (p<0.001) between 1984-2019. Young-onset CLL rates increased by 46.69%/year (p=0.236) during 1978-1980, then declined by -1.85%/year (p<0.001) from 1980 to 2019. In contrast, >75 years old's IBMR increased by 14.00%/year (p<0.001) between 1978-1982 followed by a steady increase of 1.30%/year between 1982-2019. Whites’ IBMR increased from 1978 till 2012, then plateaued at a rate of -0.10%/year (p=0.857) until 2019. Blacks’ IBMR increased by 7.65%/year (p<0.001) between 1978-1991 followed by an insignificant decline of -4.87%/year (p=0.063) from 1991-2000 and an increase of 1.40%/year (p=0.056) between 2000-2019. (Figure) Conclusion: Our findings showed a decline in CLL incidences since 2013, with plateauing of mortality rates since 2012 which is in line with recent advances in the management of CLL. Additionally, our study demonstrated improved mortality rates among the black population and those <75 years of age. Further studies will be needed to better characterize the effect of newer targeted therapies on IBMRs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Autoimmune cytopenias in chronic lymphocytic leukemia: a growing challenge in targeted therapies?

As the world’s population ages, the incidence of chronic lymphocytic leukemia (CLL) will continue to increase. CLL-related autoimmune cytopenias (AICs) are becoming a growing challenge in daily clinical practice. AICs occur in c.10% of CLL patients, and include autoimmune hemolytic anemia, immune thrombocytopenia, pure red cell aplasia, and autoimmune granulocytopenia. The complication can appear at any disease stage, both in treated and previously untreated patients. In some cases, AICs precede the diagnosis of the underlying disease. The diagnostic process of autoimmune complications is often difficult. First of all, however, it requires differentiation from bone marrow infiltration resulting from underlying disease progression. A properly established diagnosis has prognostic and therapeutic implications. Autoimmune cytopenias are more often associated with high-risk CLL (with 17p deletion, 11q deletion, wild-type variant of gene encoding immunoglobulin heavy chain variable region) and show a complex pathogenesis. CLL cells and the surrounding microenvironment are involved in autoimmune mechanisms. Treatment of AICs depends on CLL stage. In the case of isolated symptoms of AICs, without accompanying features of CLL progression, glucocorticosteroids or rituximab are recommended in the first line treatment. No response or a suboptimal response to treatment implies further therapeutic decisions. According to significant advances in the treatment of chronic lymphocytic leukemia, therapeutic strategies for autoimmune cytopenias also need to be optimized. The widespread introduction of ibrutinib, idelalisib, and venetoclax has highlighted the need for understanding the interplay between targeted therapies and AICs.

Real-world evidence of impact of atrial fibrillation (AF) on clinical and economic outcomes in patients with chronic lymphocytic leukemia (CLL).

e18729 Background: While the incidence of AF in CLL has been increasing, the implications of AF in real-world CLL patients remain understudied. This study aimed to assess the impact of AF on clinical and economic outcomes in CLL patients. Methods: This retrospective observational study used the US IBM MarketScan® commercial claims/Medicare supplement database (2017-2020) to identify newly diagnosed CLL patients (≥18 years) and incidence of AF after index date, defined as the first CLL diagnosis date. Patients were followed for ≥3-months pre-index, and from index to last follow-up or death. In addition to patient characteristics, clinical outcomes (incidence of heart failure [HF], bleeding and stroke) and economic outcomes (costs and healthcare resource utilization [HRU]) were compared between CLL patients with AF (CLL+AF) and CLL patients without AF (CLL-AF). HRU was evaluated by inpatient, outpatient, ER, and pharmacy visits. Multivariable regression analyses were conducted to examine the association between AF and clinical outcomes. Results: Among a total of 16,800 newly diagnosed CLL patients included in the study, 20% developed AF. CLL+AF were significantly older than CLL-AF (median: 77 vs 62 years; P &lt; .001). Compared to CLL-AF, CLL+AF also had significantly more comorbidities at baseline, as shown by higher Charlson comorbidity index (CCI) (median: 1.0 vs 3.0; P &lt; .001) and more patients with previous AF history (0.3% vs 8.4%; P &lt; .001). Further assessing clinical outcomes in CLL+AF vs CLL-AF, significantly higher incidence of HF (26.3% vs 3.0%; P &lt; .001), bleeding (12.2% vs 4.8%; P &lt; .001) and stroke (6.6% vs 1.2%; P &lt; .001) were observed. For HRU, CLL+AF were reported to have significantly higher rates of ER visits (29.4% vs 12.9%; P &lt; .001) and hospitalizations (42.2% vs 14.5%; P &lt; .001) than CLL-AF. In CLL+AF, the average total AF-related costs were $13,520.21 within 30 days after AF diagnosis, and $22,304.82 within 60 days after AF diagnosis. Controlling for demographics and comorbidities, multivariable regressions reported statistically significant associations between AF and HF, as well as AF and stroke (Table). Conclusions: This real-world study reported significantly higher incidence of HF, bleeding and stroke incurred by CLL patients who developed AF compared with those who did not. The presence of HF, bleeding and stroke further increased HRU and costs. These findings highlight the importance of better disease management and treatment selection to prevent AF in CLL patients.[Table: see text]

Oncoguía de leucemia linfocítica crónica

The chronic lymphocytic leukemia (CLL) diagnosis increases with age. We do not know CLL incidence in Mexico. Some risk factors for developing CLL are the inherited predisposition, monoclonal lymphocytosis, history of cancer and, probably, some infections. The diagnosis is established with a complete medical history, physical examination, and laboratory tests, among them, cytogenetic ones. The treatment choice will depend on age, performance status, comorbidities, cytogenetic alterations, clinical stage. In Oncoguía de leucemia linfocítica crónica, we include the criteria to begin treatment, and the drugs approved internationally and in our country. Likewise, we comprise the response criteria to the treatment and the recommendations for the support treatment.

Trends in Disease Burden of Chronic Lymphocytic Leukemia at the Global, Regional, and National Levels From 1990 to 2019, and Projections Until 2030: A Population-Based Epidemiologic Study

BackgroundThe prognosis of chronic lymphocytic leukemia (CLL) has been improved dramatically, but there are limited studies focusing on CLL disease burden on a global scale. We aimed to evaluate the accurate assessment of the disease burden of CLL that may provide more detailed epidemiological information for rational policies.MethodsThe main source of the data was the Global Burden of Disease (GBD) study 2019. Incident cases, death cases, disability-adjusted life years (DALYs), and their corresponding age-standardized rates (ASRs) from 1990 to 2019 were used to describe the burden of CLL. Data about attributable risk factors were also extracted and analyzed. Bayesian age-period-cohort (BAPC) models were used to assess and project the incidence and mortality rates till 2030.ResultsGlobally, the incidence of CLL had been increasing. Deaths and DALYs decreased slightly. The burden of death and DALY is affected by socio-demographic index (SDI). The incidence rate, death rate, and DALY rate of CLL increased significantly with age. Male-to-female ratios of incidence rates varied in different SDI quintiles. Smoking, high body mass index, and occupational exposure to benzene or formaldehyde were the potential risk factors related to CLL. Global ASIRs might tend to increase until 2030, while ASDR would decrease until 2030.ConclusionThe disease burden of CLL decreased in higher SDI countries but increased in lower ones. Strategies for early detection of asymptomatic CLL, development of novel drugs, and measures against attributable factors should be implemented to combat CLL burden.

POSB412 Direct and Indirect Costs Associated with Chronic Lymphocytic Leukemia in Slovakia: 5 Years' Overview

The main study objective was to calculate direct and indirect costs associated with the Chronic Lymphocytic Leukemia (CLL) in Slovakia. Due to continual increase in CLL prevalence and incidence, it is important to have more accurate insight into CLL overall burden. CLL typically progresses more slowly than other types of leukemia and in 2019 we treated more than 4000 patients.

Chronic lymphocytic leukemia in a farmer and vegetable seller: Associated with exposure of multiple work-related hazards?

There are several risk factors associated with the incidence of chronic lymphocytic leukaemia (CLL), namely genetic factors, smoking, and occupational exposure to chemicals. We highlight a possible association of a CLL case and the occupational. We reported a case of CLL patient, a 69-year-old man, who had been working as a vegetable seller and a chili farmer since 15 and 4 years ago, respectively. The patient was diagnosed with CLL three months prior to admission and had a history of three times blood transfusions. The patient only complained of paleness and weakness without any specific symptoms. No swelling of the lymph nodes, hepatomegaly, or splenomegaly was found. As a vegetable seller and chili farmer, the patient was exposed to five hazards, physical, chemical, biological, ergonomic to psychosocial. Therefore, it is necessary to analyse whether there was an association between the patient's work and the current CLL. To diagnose occupational diseases, several steps are needed. In this patient, one of the risk factors that could lead to CLL was exposure to chemicals such as pesticides. However, information regarding the content of pesticides used was unclear and there were no results obtained from pesticides biomarker examination that might cause the disease, making it difficult to establish a definitive diagnosis of work-related cause. The patient could be advised to have biomarkers of pesticide substances checked, which requires control of farmers and vegetable sellers who might have been exposed to pesticides. The control mechanism might be started from elimination, substitution, engineering, administration, and use of personal protective equipment. A control mechanism is necessary to prevent the entry of contaminants into the body, especially through inhalation, oral, and dermal pathways. It is recommended to examine for biomarkers of pesticides containing organophosphates, organochlorines, or carbamates to determine the chronic effects on the accumulation of these chemicals that might cause CLL.

Chronic Lymphocytic Leukemia In Farmer And Vegetable Seller

Background: One of the risk factors for Chronic Lymphocytic Leukemia (CLL) is chemical exposure at work. The aim is to determine the relationship between patient who work as a farmer and vegetable seller with the incidence of CLL.Case presentation: A-69-year-old man who has been working as a vegetable seller since 15 years and a chili farmer since 4 years ago. The patient was diagnosed with CLL. In his work as a vegetable seller and chili farmer, the patient gets five hazards ranging from physical, chemical, biological, ergonomic and psychosocial hazards so it is necessary to analyze whether there is a relationship between the patient’s work and the current CLL disease.Discussion: There are seven steps needed in the enforcement of occupational diseases. In addition, additional examinations are needed to determine the biomarkers of pesticides that can cause disease. This requires control for farmers and vegetable sellers who may be exposed to pesticides found in vegetables and chilies. Conclusion: Vegetable seller and farmer have potential hazards, especially chemicals contained in pesticides which have a risk relationship with the incidence of CLL. However, to cause CLL, sufficient doses are required which are influenced by occupation, intensity of use and the type of specific chemical without the need for a long duration of exposure.

Effectiveness of PPE For Prevention of Occupational Ocular Injury

Background: One of the risk factors for Chronic Lymphocytic Leukemia (CLL) is chemical exposure at work. The aim is to determine the relationship between patient who work as a farmer and vegetable seller with the incidence of CLL.Case presentation: A-69-year-old man who has been working as a vegetable seller since 15 years and a chili farmer since 4 years ago. The patient was diagnosed with CLL. In his work as a vegetable seller and chili farmer, the patient gets five hazards ranging from physical, chemical, biological, ergonomic and psychosocial hazards so it is necessary to analyze whether there is a relationship between the patient’s work and the current CLL disease.Discussion: There are seven steps needed in the enforcement of occupational diseases. In addition, additional examinations are needed to determine the biomarkers of pesticides that can cause disease. This requires control for farmers and vegetable sellers who may be exposed to pesticides found in vegetables and chilies. Conclusion: Vegetable seller and farmer have potential hazards, especially chemicals contained in pesticides which have a risk relationship with the incidence of CLL. However, to cause CLL, sufficient doses are required which are influenced by occupation, intensity of use and the type of specific chemical without the need for a long duration of exposure.

Outcome of Patients with Chronic Lymphocytic Leukemia (CLL) Receiving First Line Therapy: A Swedish Nation-Wide Study on 1053 Consecutive Patients Treated between 2007 and 2013

Background: The incidence of chronic lymphocytic leukemia (CLL) in Sweden is about 500/year. Previous US data suggest that region and type of institution/hospital where patients were treated may affect outcome. Swedish results may differ as almost all CLL patients are treated within public health care, most treatment decisions are taken at therapy conferences and we have a widespread usage of yearly updated national CLL guidelines.This study investigates the outcome following 1st line CLL therapy in a well-defined population of consecutive patients in a region with complete follow-up: such data may be used as quality assurance for healthcare providers and serve as real-world control for clinical trials, selecting patients based on inclusion/exclusion criteria. The Swedish Cancer Registry and the Information Network for Cancer (INCA) gives us a unique opportunity to identify all patients diagnosed within a defined time period, thus providing a possibility to obtain data on various therapies and outcome on a nation-wide basis.Methods: This is a retrospective study on all Swedish CLL patients who received 1st line therapy due to progressive, symptomatic CLL. The time period 2007-2013 was selected to obtain sufficient follow-up. In-depth analysis of all individual patient files was performed. Cross-checked, computerized data were subject to statistical analysis. Endpoints were clinical response (IWCLL criteria), PFS, OS and safety. Type of treating hospital (local/regional/university) and geographical region was recorded. Whether choice of 1st line therapy was compliant to the national CLL guidelines was also recorded. A multivariate cox proportional hazards model was used to explore risk factors on outcome.Results: Between 2007 and 2013, all 1st line treated patients (n=1053) were identified. At 1st line treatment initiation median age was 71 years (range 31- 96) and 34% were females. Rai stages (0-I, II-IV) were 45 and 53%. Regarding performance status (PS) 96% were grade 0-2 and only 2% had grade 3-4. FISH was not introduced in routine healthcare until late in the period and was excluded in the first analysis. IGHV mutational status analysis was not compulsory. Most frequently used treatments were chlorambucil (CLB) (39%), FCR (27%) and FC (16%). Bendamustine (B) was not introduced until end of the study period thus only 6% (n=63) had received B or BR. Other regimens included for example alemtuzumab (5%), CHOP/CVP +/-R (3%) and rituximab (R) single (2%). Dosing intensity was similar across geographical regions and type of institutions.The ORR was 64% (15% CR); with CLB 43% FCR 84%, FC 75% and B/BR 75%. ORR was significantly associated with type of treatment and age but not with sex, Rai stage (p=0.051) or bulky disease.Median PFS was 19 months and at a median follow-up of 5 years, 49% of all patients remained alive. PFS and OS were both significantly associated with type of treatment (Fig 1 and 2); CLB-treated patients had a median PFS and OS of only 9 and 33 months. Usage of CLB declined during the study period, but still 1/3 of all patients (in some regions up to 44%) received 1st line CLB as late as 2013.Age, Rai stage, PS and adherence to treatment guidelines were also significantly associated with PFS and OS by univariate analyses.There was no clearcut impact on PFS and OS by type of health care institution/hospital.Multivariate analysis revealed that age, PS, treatment (all p=0.00001), Rai stage (p=0.003) and sex (p=0.02) were all significantly associated with OS, whereas adherence to guidelines was no longer significant.Infections ≥ grade III were significantly associated with type of treatment (p=0.006); CLB 19% vs FCR 30%. Richter transformation occurred in 5% of the patients. 15 % of the patients were diagnosed with a secondary malignancy equally distrubuted between types of 1st line therapy.Conclusion:This is the largest retrospective cohort of consecutive 1st line treated CLL patients from a well defined geographical region (Sweden) with a complete follow-up. All patients were identified and data were subject to in-depth analysis of every individual patient file, ensuring high quality data. We demonstrate that single-agent CLB resulted in a poor outcome and conclude that alternative modern, effective 1st line treatment alternatives must be offered to elderly patients. This study also highlights the importance of updated evidence-based guidelines and their usage across all levels of health care. [Display omitted] DisclosuresKimby:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Celgene: Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees. Andersson:Janssen-Cilag: Honoraria; Abbvie: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; roche: Speakers Bureau; GSK: Speakers Bureau. Karlsson:Abbvie: Honoraria; Janssen-Cilag: Honoraria. Mattsson:Janssen-Cilag: Honoraria; Gilead: Honoraria; Abbvie: Honoraria; Roche: Honoraria. Österborg:Pfizer: Honoraria; Abbvie: Honoraria; Celgene: Research Funding; Janssen-Cilag: Honoraria, Research Funding; Gilead: Honoraria, Research Funding. Hansson:Abbvie: Honoraria; Gilead: Honoraria, Research Funding; Janssen-Cilag: Honoraria, Research Funding.

Real-World Outcomes of Chemoimmunotherapy in Chronic Lymphocytic Leukemia (CLL) Clinical Practice: Results from a Decade of Practice in Helsinki 2005-2015

Introduction: Around 350 new CLL cases are diagnosed annually in Finland, with approximately 1800 individuals living with the disease. However, no comprehensive disease outcome studies from clinical practice have been conducted to-date. In the absence of direct head-to-head trials, robust historical control data have become requisite to complement available clinical trial data and estimate the potential effects of novel therapies in local practice. In addition, patients (pts) in routine clinical care are far more heterogeneous than those included in clinical trials. The Finnish Hematology Registry (FHR) was created to collect real-world practice outcomes in CLL and other hematological malignancies, with Finland's centralized nationwide healthcare system allowing reliable pt identification and complete follow-up. The objective of this registry study is to describe treatment and survival outcomes for CLL pts from routine practice settings.Methods: A non-interventional, retrospective study design was used to collect routine clinical practice data from the FHR. Eligible pts aged ≥18 years diagnosed with CLL and receiving 1 or more treatment lines during 2005-2015 were identified from the FHR, with groupings of pts into those treated in the early (2005-2007), middle (2008-2010) and late (2011-2015) cohort time periods. As the registry had limited CLL pt data at study start, clinical investigators accessed medical records to retrieve and validate data. We report interim results on 66 pts from the Helsinki University Hospital, Helsinki, Finland, a hospital region accounting for 30% of the total national CLL incidence. The completion and validation of the Helsinki cohort (~130 pts) is ongoing and results from the whole dataset will be presented at ASH.Results: Median age at diagnosis was 67 years and 23% had Binet stage C. Longitudinal follow-up was available from 1st to 7th or higher treatment lines. Across all treatment lines, fludarabine-cyclophosphamide-rituximab (FCR) (52%), bendamustine-rituximab (BR) (48%), fludarabine-cyclophosphamide (FC) (27%), and chlorambucil (chl) -based therapies (24%) were the most frequently used treatments. FCR (48%) and FC (27%) were frequently used in the 1st line, whereas BR (34%) was the primary choice in the 2nd line. In later lines a wide array of treatment regimens were used. Only 2 pts received the novel agent ibrutinib as part of a named patient program; no other novel agents were used in this cohort during this period.FC and FCR were initiated in equal yet constantly decreasing proportions through 2008, when FCR became most common (0% FC vs. 40% FCR). A year later in 2009, BR was introduced into clinical practice and its use increased steadily from 14% to 30% through 2014 when its use then declined. The peak year of chl monotherapy or chl-based combinations was in 2006 with 38% of pts receiving chl-based treatment. Since then chl use has decreased dramatically, to 0% in 2015.Median overall survival (OS) from the start of any given 1st line treatment was 81 months (m). Pts receiving FC (p=0,009) and FCR (p<0,001) had significantly longer median OS (79 m and 82 m respectively) compared to bendamustine/BR (62 m) when given in the 1st line. FC and FCR resulted in longer, though not statistically different, time-to-next-treatment (TTNT) compared to bendamustine/BR (77 m vs 44 m). Despite the observed practice changes over the years, there were no detectable outcome differences in 1st and 2nd line median OS between those treated in early, middle and late time periods, possibly due to limited follow-up in the later period (data not shown).Conclusions: We describe real-world treatment trends and outcomes from a decade of practice in the Helsinki region. Our results show that chemoimmunotherapies have been vigorously implemented in clinical practice. However, interim results do not show detectable improvements for OS and TTNT during this decade of treatment in the Helsinki hospital region. In the Nordics, real-world evidence has become essential when introducing novel targeted therapies into clinical practice settings, with comprehensive disease registries expanding to allow for more detailed follow-up. [Display omitted] DisclosuresJarvinen:Janssen-Cilag Oy: Employment. Mehtälä:EPID Research: Employment, Other: EPID Research is a contract research organization that performs commissioned pharmacoepidemiological studies and thus its employees have been and currently are working in collaboration with several pharmaceutical companies.. Khanfir:EPID Research: Employment, Other: EPID Research is a contract research organization that performs commissioned pharmacoepidemiological studies and thus its employees have been and currently are working in collaboration with several pharmaceutical companies.. Juuti:EPID Research: Employment, Other: EPID Research is a contract research organization that performs commissioned pharmacoepidemiological studies and thus its employees have been and currently are working in collaboration with several pharmaceutical companies.. Leval:Janssen-Cilag Ab: Employment.

Flowcytometry in Chronic B-Cell Lymphoproliferative Disorders: A Retrospective Study from a Tertiary Oncology Centre, Trivandrum, India

Introduction: Chronic B-Cell Lymphoproliferative Disorders (B- CLPD) are malignant neoplasms of B lymphocytes characterised by accumulation of mature B lymphocytes in the Bone Marrow (BM), peripheral blood, and lymphoid tissues. Multiparameter flowcytometry has become a powerful tool in diagnosing B-CLPD that identifies a clonal light-chain restricted population expressing B-cell markers. Aim: To study the morphologic and immunophenotypic profile of B-CLPD by flowcytometry and to determine the incidence of various subtypes. Materials and Methods: All consecutively diagnosed cases of chronic B lymphoproliferative disorders at Regional Cancer Centre, Trivandrum, Kerala, India from 1st December 2016 to 30th November 2018 were retrospectively analysed and studied. Diagnosis of CLPD was made based on peripheral smear and BM aspiration and immunophenotyping by flowcytometry. Flowcytometry was performed using BD FACS Verse flowcytometer. The results of immunophenotyping by flowcytometry were reviewed and analysed. Results: During the study period, 231 cases were diagnosed as Chronic Lymphoproliferative Disorder (CPLD), of which 209 cases were B-CLPDs. Male to female ratio (M:F) was 2:1. In the present study, incidence of Chronic Lymphocytic Leukaemia (CLL) was 138 cases (66.03%), Follicular Lymphoma (FL) was 14 cases (6.7%), Hairy Cell Leukaemia (HCL) was 11 cases 5.26% and Mantle Cell Lymphoma (MCL) was 9 cases, (4.31%). Prolymphocytic leukaemia and splenic Marginal Zone Lymphoma (MZL) constituted 4 cases (1.91%) each. Some cases of B-CLPDs had no definite diagnoses which were diagnosed as CD5 positive B-CLPD unclassified 13 cases (6.22%) and CD5 negative B-CLPD unclassified 16 cases (7.66%). Conclusion: Flowcytometry has helped in definite subtyping of B-CLPD in most cases. Most common subtype in the present study was CLL. CD5+/CD23+ is highly specific for diagnosing CLL. CD200 is revealed to be an excellent marker to distinguish CLL from MCL.

Epidemiology, longitudinal treatment patterns and outcomes of chronic lymphocytic leukemia in Israel

This study aims to describe chronic lymphocytic leukemia (CLL) epidemiology, treatment patterns and outcomes in a 2.3-million-member healthcare provider database (Maccabi Healthcare Services, Israel). Newly-diagnosed CLL patients (1999–2017) were followed through 31/3/2018. A total of 1857 newly-diagnosed CLL patients were included. Annual incidence was 5.82 per 100,000 population. Median overall survival (OS) was 12.7 (95%CI: 11.8–13.5) years since diagnosis. Approximately 1/3 initiated treatment within 5 y. A statistical trend (p = 0.066) for improved OS over time was observed among younger patients (age <70 y) treated in 2009–2017 vs. 1999–2008). Among patients treated since 2009 (n = 411; median age = 68y), fludarabine–cyclophosphamide–rituximab (FCR), bendamustine–rituximab and obinutuzumab ± chlorambucil accounted for 19.5%, 12.2% and 11.4% of first line, respectively. Median (95%CI) time to next treatment and OS were 3.1(2.6–3.6) and 7.0(6.3–7.7) years, respectively. CLL incidence in Israel is comparable to developed countries. Real-world data suggest a trend of improved survival over the last decade among patients treated before age 70.

Influence of Rurality, Race, and Ethnicity on Non-Hodgkin Lymphoma Incidence

IntroductionExposure to lymphomagens vary by geography. The extent to which these contribute to racial and ethnic disparities in non-Hodgkin lymphoma (NHL) incidence is not well understood. We sought to evaluate the association between urban–rural status and racial and ethnic disparities in the 3 major NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). Patients and MethodsWe used data on NHL incidence from 21 Surveillance, Epidemiology, and End Results (SEER) population-based registries for the period 2000 to 2016. Population characteristics were compared by NHL subtype and urban–rural status, using rural-urban continuum codes from the US Department of Agriculture. Incidence rate ratios were calculated, and Poisson regression was used to assess the association between incidence and rurality. ResultsA total of 136,197 DLBCL, 70,882 FL, and 120,319 CLL incident cases aged ≥ 20 years were reported. The majority of DLBCL patients were non-Hispanic white (73.5%), with 11.9% Hispanic and 7.3% non-Hispanic black, with a similar distribution observed in FL and CLL. Adjusting for age, sex, and family poverty, we found increased DLBCL incidence among Hispanics in increasingly urban areas compared to rural areas (rural incidence rate ratio [IRR] = 1.00; nonmetropolitan urban IRR = 1.32, 95% CI 1.16, 1.51; metropolitan urban IRR = 1.55, 95% CI 1.36, 1.76). Among non-Hispanic blacks, urban areas, relative to rural areas, were associated with increased CLL incidence (IRR = 1.48; 95% CI 1.27, 1.72). ConclusionUrban–rural incidence patterns suggest that environmental exposures in urban areas associated with DLBCL and CLL pathogenesis may disproportionately affect Hispanics and non-Hispanic blacks.