Targeting of inflammatory pathways with R2CHOP in high-risk DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma, and front line therapies have not improved overall outcomes since the advent of immunochemotherapy. By pairing DNA and gene expression data with clinical response data, we identified a high-risk subset of non-GCB DLBCL patients characterized by genomic alterations and expression signatures capable of sustaining an inflammatory environment. These mutational alterations (PIM1, SPEN, and MYD88 [L265P]) and expression signatures (NF-κB, IRF4, and JAK-STAT engagement) were associated with proliferative signaling, and were found to be enriched in patients treated with RCHOP that experienced unfavorable outcomes. However, patients with these high-risk mutations had more favorable outcomes when the immunomodulatory agent lenalidomide was added to RCHOP (R2CHOP). We are the first to report the genomic validation of a high-risk phenotype with a preferential response towards R2CHOP therapy in non-GCB DLBCL patients. These conclusions could be translated to a clinical setting to identify the ~38% of non-GCB patients that could be considered high-risk, and would benefit from alternative therapies to standard RCHOP based on personalized genomic data.

Impact of lymphoma survivorship clinic visit on patient-centered outcomes.

PURPOSE: Cancer survivors may experience physical, social, and emotional effects of cancer and its treatments. National Comprehensive Cancer Network (NCCN) guidelines recommend the development of a survivorship care plan (SCP) for cancer patients following completion of treatment with curative intent. Our institution developed a lymphoma survivorship clinic (SC) to assess patient needs, provide education, and create and deliver SCPs. This study analyzed the impact of a SC visit on patient-centered outcomes. METHODS: Surveys were sent to lymphoma patients at Mayo Clinic Rochester within 4 weeks of their post-treatment visit to the SC that queried patient-reported outcomes, including experience of care, quality of life (QOL), and distress. We compared survey responses between those who attended the SC and those who were eligible but did not attend. RESULTS: From November 2013 to May 2015, 236 lymphoma patients were surveyed, 96 of whom had a SC visit and 140 of who were eligible but did not attend. Those who attended the SC were more likely to "definitely" recall discussion on improving health, preventing illness, and making changes in habits/lifestyle, diet, and exercise. There were no differences in QOL or distress. Adjusted analyses revealed that SC attendance was associated with better self-reported overall health among younger patients and better physical well-being in Hodgkin lymphoma patients compared to those with other subtypes of lymphoma. CONCLUSIONS: Participation in the lymphoma SC improved patient education on survivorship issues, particularly health behaviors. There may be a particular benefit in younger patients. However, there were no differences in QOL or distress. Further study is needed to determine if improved survivorship education and SCP delivery leads to long-term health benefits in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Our study evaluates the clinical impact of a SC in patients treated for lymphoma. We demonstrate that a SC visit improves patient education regarding health behaviors.

Low Plasma Omega-3 Fatty Acid Levels May Predict Inferior Prognosis in Untreated Diffuse Large B-Cell Lymphoma: A New Modifiable Dietary Biomarker?

Dietary factors that may reduce the risk of relapse or prolong remission are an area of interest for patients with cancer. There is little data on the role of omega-3 fatty acids (n-3 FA) in patients diagnosed with lymphoma. This pilot biomarker study evaluated the prognostic significance of n-3 FA levels in patients with diffuse large B-cell lymphoma (DLBCL). In this analysis, low n-3 FA may be associated with inferior event free survival at 24 months in this disease. Larger studies are needed to confirm this association and could provide the basis for prospective investigation of whether modifying n-3 levels with diet may improve outcome in lymphoma.

Widespread use of complementary and alternative medicine among non-Hodgkin lymphoma survivors.

There are few studies examining complementary and alternative medicine (CAM) use and beliefs among non-Hodgkin lymphoma (NHL) survivors. Seven hundred and nineteen patients with NHL from the University of Iowa/Mayo Clinic Molecular Epidemiology Resource who completed the 3-year post-diagnosis questionnaire were included in this study. Altogether 636 (89%) reported ever using CAM, with 78% utilizing vitamins, 54% alternative therapies and 45% herbals. Female gender was associated with increased overall CAM use (p=0.0001) as well as use of vitamins (p=0.0001), herbals (p=0.006) and alternative therapy (p=0.0002) for cancer. Older age (>60) was associated with increased vitamin use (p=0.005) and decreased herbal use (p=0.008). Among users, 143 (20%) believed CAM assists healing, 123 (17%) believed CAM relieves symptoms, 122 (17%) believed CAM gives a feeling of control, 110 (15%) believed CAM assists other treatments, 108 (15%) believed CAM boosts immunity, 26 (4%) believed CAM cures cancer and 36 (5%) believed CAM prevents the spread of cancer.

Medical history, lifestyle, family history, and occupational risk factors for mantle cell lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

BACKGROUND: The etiology of mantle cell lymphoma (MCL), a distinctive subtype accounting for 2%-10% of all non-Hodgkin lymphoma, is not known. METHODS: We investigated associations with self-reported medical history, lifestyle, family history, and occupational risk factors in a pooled analysis of 557 patients with MCL and 13766 controls from 13 case-control studies in Europe, North America, and Australia. Odds ratios (ORs) and 95% confidence intervals (CIs) associated with each exposure were examined using multivariate logistic regression models. RESULTS: The median age of the MCL patients was 62 years and 76% were men. Risk of MCL was inversely associated with history of hay fever (OR = 0.63, 95% CI = 0.48 to 0.82), and the association was independent of other atopic diseases and allergies. A hematological malignancy among first-degree relatives was associated with a twofold increased risk of MCL (OR = 1.99, 95% CI = 1.39 to 2.84), which was stronger in men (OR = 2.21, 95% CI = 1.44 to 3.38) than women (OR = 1.61, 95% CI = 0.82 to 3.19). A modestly increased risk of MCL was also observed in association with ever having lived on a farm (OR = 1.40, 95% CI = 1.03 to 1.90). Unlike some other non-Hodgkin lymphoma subtypes, MCL risk was not statistically significantly associated with autoimmune disorders, tobacco smoking, alcohol intake, body mass index, or ultraviolet radiation. CONCLUSIONS: The novel observations of a possible role for atopy and allergy and farm life in risk of MCL, together with confirmatory evidence of a familial link, suggest a multifactorial etiology of immune-related environmental exposures and genetic susceptibility. These findings provide guidance for future research in MCL etiology.

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.

Food-frequency questionnaire-based estimates of total antioxidant capacity and risk of non-Hodgkin lymphoma.

Antioxidants, primarily from fruits and vegetables, have been hypothesized to protect against non-Hodgkin lymphoma (NHL). The oxygen radical absorbance capacity (ORAC) assay, which measures total antioxidant capacity of individual foods and accounts for synergism, can be estimated using a food-frequency questionnaire (FFQ). We tested the hypothesis that higher intake of antioxidant nutrients from foods, supplements and FFQ-based ORAC values are associated with a lower risk of NHL in a clinic-based study of 603 incident cases and 1,007 frequency-matched controls. Diet was assessed with a 128-item FFQ. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals adjusted for age, sex, residence and total energy. Dietary intake of α-tocopherol (OR=0.50; p-trend=0.0002), ß-carotene (OR=0.58; p-trend=0.0005), lutein/zeaxanthin (OR=0.62; p-trend=0.005), zinc (OR=0.54; p-trend=0.003) and chromium (OR=0.68; p-trend=0.032) was inversely associated with NHL risk. Inclusion of supplement use had little impact on these associations. Total vegetables (OR=0.52; p-trend<0.0001), particularly green leafy (OR=0.52; p-trend<0.0001) and cruciferous (OR=0.68; p-trend=0.045) vegetables, were inversely associated with NHL risk. NHL risk was inversely associated with both hydrophilic ORAC (OR=0.61, p-trend=0.003) and lipophilic ORAC (OR=0.48, p-trend=0.0002), although after simultaneous adjustment for other antioxidants or total vegetables, only the association for lipophilic ORAC remained significant. There was no striking heterogeneity in results across the common NHL subtypes. Higher antioxidant intake as estimated by the FFQ-ORAC, particularly the lipophilic component, was associated with a lower NHL risk after accounting for other antioxidant nutrients and vegetable intake, supporting this as potentially useful summary measure of total antioxidant intake.

Antioxidant intake from fruits, vegetables and other sources and risk of non-Hodgkin's lymphoma: the Iowa Women's Health Study.

Antioxidant nutrients found in fruits, vegetables and other foods are thought to inhibit carcinogenesis and to influence immune status. We evaluated the association of these factors with risk of non-Hodgkin's lymphoma (NHL) overall and for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma specifically in a prospective cohort of 35,159 Iowa women aged 55-69 years when enrolled at baseline in 1986. Diet was ascertained using a validated semiquantitative food frequency questionnaire. Through 2005, 415 cases of NHL (including 184 DLBCL and 90 follicular) were identified. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox regression, adjusting for age and total energy. The strongest associations of antioxidants with risk of NHL (RR for highest versus lowest quartile; p for trend) were observed for dietary vitamin C (RR = 0.78; p = 0.044), alpha-carotene (RR = 0.71; p = 0.015), proanthocyanidins (RR = 0.70; p = 0.0024) and dietary manganese (RR = 0.62; p = 0.010). There were no associations with multivitamin use or supplemental intake of vitamins C, E, selenium, zinc, copper or manganese. From a food perspective, greater intake of total fruits and vegetables (RR = 0.69; p = 0.011), yellow/orange (RR = 0.72; p = 0.015) and cruciferous (RR = 0.82; p = 0.017) vegetables, broccoli (RR = 0.72; p = 0.018) and apple juice/cider (RR = 0.65; p = 0.026) were associated with lower NHL risk; there were no strong associations for other antioxidant-rich foods, including whole grains, chocolate, tea or nuts. Overall, these associations were mainly observed for follicular lymphoma and were weaker or not apparent for DLBCL. In conclusion, these results support a role for vegetables, and perhaps fruits and associated antioxidants from food sources, as protective factors against the development of NHL and follicular lymphoma in particular.

Complementary and alternative medicine use among long-term lymphoma survivors: a pilot study.

No published survey has specifically addressed the beliefs, knowledge, and usage of complementary and alternative medicine (CAM) in long-term (5-20 years) lymphoma survivors alone. In this pilot project, 95 subjects were randomly selected from a population of 2,475 long-term lymphoma survivors and mailed a questionnaire. The median time from lymphoma diagnosis to completion of the questionnaire was 11 years (range 6-20). Overall, 68% (95% CI: 54-80%) of the long-term lymphoma survivors reported that they have used CAM, a rate higher than the estimated usage rate reported for the general population The most commonly used modalities were chiropractic (39%, 95% CI: 27-53%) and massage therapy (21%, 95% CI: 12-34%). Less than 10% used meditation (5%, 95% CI: 1-15%) and relaxation (7%, 95% CI: 2-17%). In terms of common herbal usage, 5% (95% CI: 1-15%) had used St. John's Wort and 7% (95% CI: 2-17%) had used shark cartilage. Although none of the patients reported that CAM usage was directed specifically towards treating their lymphoma, 4% (95% CI: 0-12%) of patients reported that CAM could cure cancer, and 14% (95% CI: 6-26%) reported that CAM could increase their feeling of control over their health. This pilot study suggests that long-term lymphoma survivors appear to use CAM at a rate higher than the general population. The use of potential agents of risk by the survivors and the lack of access to potentially beneficial modalities highlights the need for further study of CAM in this population.

Therapeutic options in patients with lymphoma and severe liver dysfunction.

OBJECTIVES: To determine the long-term outcome of patients presenting with synchronous lymphoma and severe liver dysfunction and to describe the outcome of patients treated with initial mechlorethamine-based therapy used as a bridge to more conventional chemotherapy. PATIENTS AND METHODS: We reviewed the clinical course of all patients diagnosed as having lymphoma who presented with severe liver dysfunction and received intravenous mechlorethamine between September 1988 and February 2003 at the Mayo Clinic in Rochester, Minn. RESULTS: Forty-one patients were identified, 33 (80%) of whom had newly diagnosed, previously untreated lymphoma. Thirty-seven (90%) had non-Hodgkin lymphoma, and 4 (10%) had Hodgkin disease. Thirty-four patients (83%) had stage IV disease, and 31 (84%) of 37 had an intermediate-high International Prognostic Index. The median total bilirubin level before therapy was 10.7 mg/dL (range, 2.5-30.2 mg/dL), and the median alkaline phosphatase level was 982 U/L (range, 233-3415 U/L). In addition to mechlorethamine, 34 patients (83%) received concomitant corticosteroids, and 12 (29%) received concomitant rituximab. Twenty-two patients (54%) had sufficient improvement in liver function to receive subsequent standard chemotherapy. Nine patients (22%) are alive and disease-free at a median of 31 months (range, 4 to > or = 87 months) after mechlorethamine treatment. Factors associated with improved overall survival included improvement in bilirubin levels (P < .001) and receiving subsequent standard chemotherapy (P = .001). CONCLUSION: Mechlorethamine, high-dose corticosteroids, and rituximab are useful therapeutic interventions for this unique group of patients with lymphoma and severe liver dysfunction. Substantial clinical improvement and long-term survival are possible.