A prospective analysis of red blood cell membrane polyunsaturated fatty acid levels and risk of non-Hodgkin lymphoma.

Published studies report inconsistent associations of polyunsaturated fatty acid (PUFA) intake with non-Hodgkin lymphoma (NHL) risk. We conducted a nested case-control study in Nurses' Health Study and Health Professionals Follow-Up Study participants to evaluate a hypothesis of inverse association of pre-diagnosis red blood cell (RBC) membrane PUFA levels with risk of NHL endpoints. We confirmed 583 NHL cases and matched 583 controls by cohort/sex, age, race and blood draw date/time. We estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL endpoints using logistic regression. RBC PUFA levels were not associated with all NHL risk; cis 20:2n-6 was associated with follicular lymphoma risk (OR [95% CI] per one standard deviation increase: 1.35 [1.03-1.77]), and the omega-6/omega-3 PUFA ratio was associated with diffuse large B-cell lymphoma risk (2.33 [1.23-4.43]). Overall, PUFA did not demonstrate a role in NHL etiology; the two unexpected positive associations lack clear biologic explanations.

Association between Meat, Fish, and Fatty Acid Intake and Non-Hodgkin Lymphoma Incidence: The Japan Public Health Center-Based Prospective Study.

BACKGROUND: Meat, fish, and fatty acid intakes have been reported to be associated with non-Hodgkin lymphoma (NHL), although results have been inconclusive. We hypothesized that red meat and SFA intakes increase NHL risk, and fish and PUFA intakes decrease NHL risk. OBJECTIVES: We investigated the association between NHL incidence and meat, fish, and various fatty acid type intakes using the Japan Public Health Center-based Prospective Study. METHODS: The current cohort study included 93,366 participants aged 45-74 y who were eligible for analysis; they were followed up until December 2012. Participants answered an FFQ between 1995 and 1999. We analyzed the effects of meat, fish, total fatty acid, SFA, and PUFA intakes on NHL incidence using the Cox proportional hazard model. RESULTS: The median age was 57 y (IQR: 51-63 y), and 46.5% of the participants were men. Participants were followed up for 1,345,001 person-years, and 230 patients with NHL were identified. Total fatty acid and SFA intakes were associated with an increased incidence of NHL, with an adjusted HR of 1.56 (95% CI: 1.04, 2.34 highest compared with lowest quartile; P-trend = 0.062), and 1.63 (95% CI: 1.11, 2.41; P-trend = 0.074), respectively. In subtype analysis, total fatty acid and SFA intakes were also associated with increased incidence of follicular lymphoma but were not significantly associated with diffuse large B-cell lymphoma. Conversely, total meat, processed meat, unprocessed meat, red meat, poultry, fish, MUFA, PUFA, n-3 (ω-3) PUFA, and n-6 (ω-6) PUFA intakes were not significantly associated with the incidence of NHL or its subtypes. CONCLUSIONS: Total fatty acid and SFA intakes were associated with increased incidence of NHL in the Japanese adult population. Further large-scale studies are warranted to test whether fatty acid intakes affect the development of NHL.

Advances in treatment of elderly primary central nervous system lymphoma.

The management of older individuals (≥60 years) with primary central nervous system lymphoma remains a clinical challenge. Identification of optimal therapy and delivering adequate dose intensity are two of the major issues in treating elderly patients. Premorbid performance status and comorbidities influence individualised treatment approaches and geriatric assessment tools are increasingly utilised. Optimal induction treatment remains high-dose methotrexate-based immunochemotherapy, delivery is feasible in the majority of patients and the goal of treatment remains achieving complete remission. Consolidation strategies are also relevant in the elderly, aiming to maximise duration of response and quality of life (QoL). Potential options include high-dose therapy with haematopoietic stem cell consolidation, non-myeloablative chemotherapy and whole-brain radiotherapy. Efficacy of novel agents, such as Bruton tyrosine kinase inhibitors and lenalidomide, have been reported; these represent an alternative for elderly patients unfit for chemotherapy. Prognosis remains poor, improvement of outcomes in this age group is urgently needed.

No Association Observed between Coffee Intake and Risk of Non-Hodgkin Lymphoma among Postmenopausal Women.

BACKGROUND: Some preliminary studies indicate that components in coffee may have anticarcinogenic effects. However, the association between coffee-drinking habits and the risk of non-Hodgkin lymphoma (NHL) remain controversial. OBJECTIVE: To examine the relationship between coffee intake and NHL incidence in a large prospective study of postmenopausal US women. DESIGN AND PARTICIPANTS/SETTING: The participants included 74,935 women from the Women's Health Initiative Observational Study who were recruited from 1993 through 1998. Information about coffee-drinking habits was collected at baseline via self-administered questionnaires. MAIN OUTCOME MEASURES: Newly diagnosed NHL was validated by medical records and pathology records. Separate analyses were performed for the following three subtypes of NHL: diffuse large B-cell lymphoma (n = 244), follicular lymphoma (n = 166), and chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 64). STATISTICAL ANALYSES PERFORMED: Age-adjusted and multivariable-adjusted Cox proportional hazards models were used to determine associations of coffee intake (specifically, the total amount of coffee consumed daily, coffee types, and coffee preparation methods) with risk of NHL. RESULTS: A total of 851 women developed NHL during a median 18.34 years of follow-up (range = 0.01 to 24.30 years; ± 6.63 years). Overall, no associations were observed between coffee intake and risk of NHL regardless of the total amount of daily coffee intake (P value for trend = 0.90), caffeinated (P = 0.55) or decaffeinated coffee intake (P = 0.78), and filtered or unfiltered coffee intake (P = 0.91) after controlling for sociodemographic factors, lifestyle risk factors, and clinical risk factors/current medical conditions. No significant associations were observed between coffee intake with specific subtypes of NHL. A statistically significant interaction was found between alcohol intake, coffee intake, and incident NHL (P value for interaction = 0.02) based on the adjusted analysis. Specifically, among women who frequently consumed alcohol (> 7 drinks/week), those who had moderate coffee intake (2 to 3 c coffee/day) had a significantly reduced risk of developing NHL (hazard ratio 0.61, 95% CI 0.36 to 0.98), compared with those who did not drink coffee. CONCLUSIONS: The findings from this study do not support an association between coffee consumption and NHL risk, irrespective of the total amount of daily coffee intake, coffee types, or coffee preparation methods.

Successful treatment of Epstein-Barr virus-associated primary central nervous system lymphoma due to post-transplantation lymphoproliferative disorder, with ibrutinib and third-party Epstein-Barr virus-specific T cells.

Primary central nervous system lymphoma (PCNSL) occurring following organ transplantation (post-transplantation lymphoproliferative disorder [PTLD]) is a highly aggressive non-Hodgkin lymphoma. It is typically treated with high-dose methotrexate-based regimens. Outcomes are dismal and clinical trials are lacking. It is almost always Epstein-Barr virus (EBV) associated. Two patients (CA1-2) presented with EBV-associated PCNSL after renal transplant. CA1 was on hemodialysis and had prior disseminated cryptococcus and pseudomonas bronchiectasis, precluding treatment with methotrexate. CA2 was refractory to methotrexate. Both were treated off-label with the first-generation Bruton's tyrosine kinase inhibitor ibrutinib for 12 months. Cerebrospinal fluid penetration at therapeutic levels was confirmed in CA1 despite hemodialysis. Both patients entered remission by 2 months. Sequencing confirmed absence of genetic aberrations in human leukocyte antigen (HLA) class I/II and antigen-presentation/processing genes, indicating retention of the ability to present EBV-antigens. Between Weeks 10 and 13, they received third-party EBV-specific T cells for consolidation with no adverse effects. They remain in remission ≥34 months since therapy began. The strength of these findings led to an ongoing phase I study (ACTRN12618001541291).

Effects of Coffee, Black Tea and Green Tea Consumption on the Risk of Non-Hodgkin's Lymphoma: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

Aim: Several studies have evaluated the association between coffee, black and green tea consumption and non-Hodgkin's lymphoma (NHL) risk, while the results were inconsistent. We conducted a dose-response meta-analysis of available observational studies to assess the association among coffee, black and green tea intake and the risk of NHL in the general population. Methods: Studies published up to August 2018 were identified on the basis of a literature search in PubMed, ISI Web of Science, Scopus and Cochrane databases using Mesh and non-Mesh relevant keywords. Relative risks (RRs) with 95% confidence intervals (CIs) and the dose-response relationships were calculated using random-effects models. Results: In the meta-analysis of 19 effect sizes (315,972 participants with 4,914 cases of NHL), we found that higher green tea intake was associated with a 39% reduced risk of NHL (pooled RR = 0.61; 95% CIs = 0.38-0.99, I2=60.4%, pheterogeneity=0.080) in high- versus low-intake meta-analysis. No association was observed between coffee intake (pooled RR = 1.21; 95% CIs = 0.97-1.50, I2=52.6%, pheterogeneity < 0.05), black tea intake (pooled RR = 1.01; 95% CI = 0.82-1.24, I2=0%, pheterogeneity=0.875) and risk of NHL in high- versus low-intake meta-analysis. Conclusions: Findings from this dose-response meta-analysis suggest that green tea intake may be associated with reduced risk of NHL.

Risk of death for hematological malignancies for residents close to an Italian petrochemical refinery: a population-based case-control study.

PURPOSE: We investigated the risk of death for hematological malignancies (HMs) in the area surrounding an Italian petrochemical refinery, where atmospheric concentrations of benzene (known carcinogen) had not been adequately monitored in the past. METHODS: We performed a population-based case-control study, using conditional logistic regression to estimate odds ratios (ORs) of HM death, with 95 % confidence intervals (CIs), and p trends, in relation to tertiles of time-weighted average residential proximity to the refinery. We identified 177 HM deaths and 349 sex- and age-matched controls from municipal files. Confounding factors were investigated from interviews with consenting relatives for 109 HM deaths and 178 matched controls. RESULTS: For males and females combined, risk of HM death was unrelated to residential proximity. For females, ORs of HM death by increasing tertiles of proximity were 1, 2.74 (95 % CI 1.48-5.09, significant) and 1.49 (95 % CI 0.76-2.92) (p trend 0.184). For the subgroup of persons who plausibly spent most of their time at home (long-term retired, homemakers or unemployed, 53 cases, 79 controls), the ORs of leukemia plus non-Hodgkin lymphoma death (38 cases, 56 controls) by increasing tertiles of proximity were 1, 3.44 (95 % CI 1.04-11.37, significant) and 3.25 (95 % CI 0.82-12.87) (p trend 0.083). CONCLUSIONS: No increased risk of HM death for males and females combined living close to the refinery was found. However, the findings for females and a subgroup plausibly spending most of their time at home suggest a relation between increased risk of HM death and residential proximity to the refinery.

Case-control study of risk factors for Non-Hodgkin lymphoma in Mumbai, India.

BACKGROUND: In the year 2010, it is estimated that nearly 0.36 million new cases and 0.19 million deaths with Non-Hodgkin lymphoma occurred. In India, among males, NHL incidence rates vary across the country which has encouraged us to conduct a case-control study to study risk factors. MATERIALS AND METHODS: The present unmatched hospital-based case-control study conducted at Tata Memorial Hospital included subjects registered between the years 1997-99. There were 390 'lymphoma cases' and 1,383 'normal controls. RESULTS: Data on age, tobacco habits, occupational history, dietary factors, tea, coffee were collected by the social investigators. Univariate and multivariate methods were applied for obtaining the odds ratios for risk factors. CONCLUSIONS: In the study, cigarette smoking (OR=2.0) and bidi smoking (OR=2.8), were associated with excess risk of lymphoma. Among the dietary items, only consumption of mutton showed 7.3-fold significant excess risk for lymphoma. Consumption of milk showed a 6-fold excess risk (OR=1.5); while coffee showed a 50% reduction in risk for lymphoma. Among occupational exposure, exposure to use of pesticides showed 3-fold excess risk for lymphoma.

Trans fatty acid intake is associated with increased risk and n3 fatty acid intake with reduced risk of non-hodgkin lymphoma.

We evaluated the association of dietary fat and protein intake with risk of non-Hodgkin lymphoma (NHL) in a clinic-based study in 603 cases (including 218 chronic lymphocytic leukemia/small lymphocytic lymphoma, 146 follicular lymphoma, and 105 diffuse large B-cell lymphoma) and 1007 frequency-matched controls. Usual diet was assessed with a 128-item food-frequency questionnaire. Unconditional logistic regression was used to estimate ORs and 95% CIs, and polytomous logistic regression was used to assess subtype-specific risks. trans Fatty acid (TFA) intake was positively associated with NHL risk [OR = 1.60 for highest vs. lowest quartile (95% CI = 1.18, 2.15); P-trend = 0.0014], n3 (ω3) fatty acid intake was inversely associated with risk [OR = 0.48 (95% CI = 0.35, 0.65); P-trend < 0.0001], and there was no association with total, animal, plant-based, or saturated fat intake. When examining intake of specific foods, processed meat [OR = 1.37 (95% CI = 1.02, 1.83); P-trend = 0.03], milk containing any fat [OR = 1.47 (95% CI = 1.16, 1.88); P-trend = 0.0025], and high-fat ice cream [OR = 4.03 (95% CI = 2.80, 5.80); P-trend < 0.0001], intakes were positively associated with risk, whereas intakes of fresh fish and total seafood [OR = 0.61 (95% CI = 0.46, 0.80); P-trend = 0.0025] were inversely associated with risk. Overall, there was little evidence for NHL subtype-specific heterogeneity. In conclusion, diets high in TFAs, processed meats, and higher fat dairy products were positively associated with NHL risk, whereas diets high in n3 fatty acids and total seafood were inversely associated with risk.

Intake of vitamins D and A and calcium and risk of non-Hodgkin lymphoma: San Francisco Bay Area population-based case-control study.

Several nutrients identified as potentially cancer protective have been inconsistently associated with non-Hodgkin lymphoma (NHL) risk. Dietary history data, including use of vitamin supplements, were collected using a semiquantitative food frequency questionnaire administered during in-person interviews with 4,133 participants (2,052 cases, 2,081 controls) in a San Francisco Bay Area population-based case-control study. Data were used to determine the association of intake levels of vitamins D and A and calcium with risk of NHL and NHL subtypes. Odds ratios (OR) and 95% confidence intervals (CI) were computed as estimates of relative risk using adjusted unconditional logistic regression. Increasing vitamin D intake from food and supplements was positively associated with NHL risk in men (5th quintile: OR = 1.6, 95% CI = 1.0-2.4, P(trend) = 0.07) and with diffuse large B-cell lymphoma (DLBCL) in women and men (5th quintile: OR = 1.6, 95% CI = 1.0-2.5, P(trend) = 0.02); that was largely due to the effect in men (P(trend) = 0.03). These results do not support a strong role for vitamin D intake with NHL risk, with the exception of a potential association for DLBCL risk in men. Our results should be interpreted conservatively until further investigation in larger pooled studies can be conducted to better assess the role of vitamin D intake in lymphomagenesis.

Vitamin D and non-Hodgkin lymphoma risk in adults: a review.

Animal and human studies support a protective effect of vitamin D sufficiency related to malignancy by uncovering paracrine and autocrine effects of extra-renal 25-hydroxyvitamin D (25(OH)D) activation including regulation of cell cycle proliferation, apoptosis induction, and increased cell differentiation signaling. Recent epidemiologic studies demonstrate a reduction in non-Hodgkin lymphoma (NHL) risk with increased sunlight exposure. As sunlight is a major vitamin D source, it has been suggested that vitamin D status may mediate this observed association. This review provides a comprehensive discussion of the current epidemiologic evidence with regard to the investigation of an association between vitamin D status and NHL risk.

Fundamentals of the management of non-Hodgkin lymphoma.

The incidence of Non-Hodgkin's lymphomas (NHL) is rising worldwide and if not adequately treated carries a high mortality rate. The pattern and frequency of NHL vary in different populations and geographical regions. It has considerable biologic and clinical heterogeneity and a definitive diagnosis can be made only after histopathogical examination. The histology and the extent of the lymphoma are the major determinants of optimal therapeutic regimen and treatment outcome. Additionally, the overall treatment strategies should be tailored according to medical status and preference of the patient. A holistic approach provided by a multi-disciplinary team of health care professionals is the cornerstone of ensuring successful treatment outcome. Importantly, therapy should be expedited and where possible performed in experienced centers. Patients achieving remission would require long-term monitoring for disease recurrence and late effects of cytotoxic chemotherapy and radiotherapy. Hence, clinicians should have a fundamental understanding in the biology and the principles of treatment of NHL. This review provides an evidence-based and systematic approach in designing therapeutic strategies for individual patients with newly diagnosed and relapsed NHL focusing on the common types of NHL with particular reference to the current practice within the local settings. The role of standard and novel therapeutic modalities in treatment will be summarized.

Combining systemic retinoids with biologic agents for moderate to severe psoriasis.

BACKGROUND: Moderate to severe psoriasis, which is defined as psoriasis affecting more than 20% of the body surface area, often requires a combination of therapies to achieve remission. Although numerous data exist regarding the use of acitretin and biologic agent therapy alone for psoriasis, little is known about the efficacy, safety, and tolerability of acitretin combined with biologic agents. METHODS: Fifteen patients with psoriasis treated with concomitant acitretin and a biologic agent were identified, and their charts were reviewed for response to therapy, additional therapy necessary for disease management, side-effects, and laboratory abnormalities whilst on combination therapy. The Institutional Review Board did not require approval for this chart review. RESULTS: Twenty-nine per cent of patients showed clearance of psoriasis, 43% of patients showed an improvement of 90%, 14% showed an improvement of 75%, and 7.1% showed no change. During treatment with acitretin and biologic agent, five patients required no adjunctive treatment. Three patients were able to stop narrow-band ultraviolet-B (UV-B) therapy after an average of 2.33 months of combination therapy. Only one patient continued to require phototherapy (UV-B) in addition to the biologic agent. Three patients developed squamous cell carcinoma (SCC) whilst on combination therapy, but all patients had a previous history of SCC. One patient developed non-Hodgkin's lymphoma after 3 years of etanercept and acitretin, and the etanercept was discontinued. CONCLUSIONS: Acitretin combined with biologic agents offers a promising method of managing refractory psoriasis. More research is needed to determine the long-term safety and efficacy of this combination.

Hair selenium status in children with leukemia and lymphoma.

Selenium (Se) is a trace element contributing to the structure of antioxidant system that saves cells from reactive oxygen species. Low serum Se levels have been reported in pediatric and adult patients with cancers. On the other hand, hair Se levels, predicting the long-term body Se status, have been reported in only adult patients with cancer. The aim of the study was to investigate the hair Se status in children with newly diagnosed lymphoid malignancies and the relation between malnutrition and Se deficiency. Thirty patients with leukemia (n=17) and lymphoma (n=13), and 25 healthy controls were enrolled to the study. Se was determined with atomic absorption spectrophotometrical method. Hair Se levels of the patients were significantly lower than those of control group [666.96+/-341.46 ng/g vs. 1019.22+/-371.83 ng/g (P<0.001)]. Children with lymphoma had lower Se than the children with acute lymphoblastic leukemia but not statistically significant [547.03+/-283.67 ng/g vs. 758.67+/-361.05 ng/g (P>0.05)]. Malnourished patients (11/30) had lower hair Se levels (483.51+/-235.55 ng/g) than those of the controls (P=0.036), whereas the Se levels of the patients who had no malnutrition (773.17+/-352.92 ng/g) were also lower than those of the controls but not statistically significant (P=0.053). There was no correlation between age, sex, and the hair Se levels. In this study, we found that hair Se levels of the children with leukemia and lymphoma, especially those of malnourished patients, were lower than those of controls. Additional studies are needed to determinate whether low levels of hair Se may play a role in carcinogenesis.

Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years?

Primary gastric (PG) lymphomas are generally non-Hodgkin lymphomas (NHL). They represent 5% of gastric malignancies and show an apparently increasing incidence worldwide. The most common histological subtypes are diffuse large B-cell and marginal zone B-cell NHL of the mucosa-associated lymphoid tissue (MALT)-type. Pathogenesis is often related to Helicobacter pylori infection (HPI). There is still no consensus on the optimal treatment for PG lymphoma. Nowadays surgery is limited to rare cases and radiotherapy--combined or not with chemotherapy--represents an effective therapeutic option ensuring long-term, organ-salvage benefits mainly in aggressive histological subtypes. Additionally, the description of MALT lymphomas has made the situation even more complex, because antibiotics alone can induce lasting remissions in those cases associated with HPI. Consequently, a global therapeutic approach to the cure of PG-NHL has completely changed over the last 10 years: innovative, conservative options to reduce treatment toxicity, thus preventing systemic relapses, have made their appearance and are on the rise.

Ultraviolet radiation, dietary vitamin D, and risk of non-Hodgkin lymphoma (United States).

OBJECTIVE: Because of conflicting findings about the relationship between ultraviolet (UV) radiation and the risk of non-Hodgkin lymphoma (NHL), we evaluated the risk of several indicators related to UV, including two not previously studied: dietary vitamin D, and ambient UV levels by residential location. METHODS: As part of a case-control study conducted in four Surveillance, Epidemiology, and End Results (SEER) registries, we collected UV information from a self-administered questionnaire and computer-assisted personal interview with 551 NHL cases and 462 controls. We estimated the relative risk (RR) and 95% confidence intervals (CI) from unconditional logistic regression models. RESULTS: Eye color, a marker of host susceptibility to UV, showed a decreasing risk gradient for lightest eyes (0.47) compared to darkest. Relative risks were in the range of 0.73-0.78 for participants reporting more hours in the mid-day summer sun. Use of sunlamps or tanning booths was associated with decreased risk (RR = 0.88), as was estimated overall ambient UV (RR = 0.76 per 50 RB-units) overall. Vitamin D intake from diet and supplements was not related to risk. Results were thus consistent for the various indicators, although some estimated risks were not statistically significant. Effects were generally similar for diffuse large B-cell (DLBCL) and follicular lymphomas. CONCLUSION: These data suggest a slight protective effect of sunlight against NHL, and they agree with geographic patterns of NHL incidence observed in the US.

Health Watch exposure estimates: do they underestimate benzene exposure?

A nested case-control study found that the excess of leukemia, identified among the male members of the Health Watch cohort, was associated with benzene exposure. Exposure had been retrospectively estimated for each individual occupational history using an algorithm in a relational database. Benzene exposure measurements, supplied by Australian petroleum companies, were used to estimate exposure for specific tasks. The tasks carried out within each job, the products handled, and the technology used, were identified from structured interviews with contemporary colleagues. More than half of the subjects started work after 1965 and had an average exposure period of 20 years. Exposure was low; nearly 85% of the cumulative exposure estimates were at or below 10 ppm-years. Matched analyses showed that leukemia risk increased with increasing cumulative benzene exposures and with increasing exposure intensity of the highest-exposed job. Non-Hodgkin lymphoma and multiple myeloma were not associated with benzene exposure. A reanalysis reported here, showed that for the 7 leukemia case-sets with greater than 16 ppm-years cumulative exposure, the odds ratio was 51.9 (5.6-477) when compared to the 2 lowest exposed categories combined to form a new reference category. The addition of occasional high exposures, e.g. as a result of spillages, increased exposure for 25% of subjects but for most, the increase was less than 5% of total exposure. The addition of these exposures reduced the odds ratios. Cumulative exposures did not range as high as those in comparable studies; however, the recent nature of the cohort and local handling practices can explain these differences.