Development and validation of a model to predict acute kidney injury following high-dose methotrexate in patients with lymphoma.

STUDY OBJECTIVE: To develop and validate a model for predicting acute kidney injury (AKI) after high-dose methotrexate (HDMTX) exposure. DESIGN: Retrospective analysis. SETTING: Multisite integrated health system throughout Minnesota and Wisconsin. PATIENTS: Adult patients with lymphoma who received HDMTX as a 4-h infusion. MEASUREMENTS AND MAIN RESULTS: LASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort. CONCLUSION: This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

Early, empiric high-dose leucovorin rescue in lymphoma patients treated with sequential doses of high-dose methotrexate.

BACKGROUND: In patients exposed to high-dose methotrexate (HDMTX; >1g/m2) with a history of elevated methotrexate (MTX) concentrations during previous doses, it is unclear whether prescribing high-dose leucovorin (HDLV) rescue limits future high levels or reduces the likelihood of acute kidney injury (AKI). METHODS: This retrospective, single-center study longitudinally followed adult lymphoma patients treated with HDMTX between 1/1/2011 and 10/31/2017 from diagnosis until 30 days after the last HDMTX dose. Endpoints included elevated MTX concentrations at 48 h (>1.0 µmol/L) and incident AKI after each HDMTX dose. RESULTS: The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. There were 1558 HDMTX doses [median (IQR) 3 (2, 6) doses per patient] prescribed with 265 (83%) patients receiving more than one MTX dose. Those receiving HDLV rescue were more likely to have an elevated MTX concentration after that dose (OR = 2.69, 95% CI: 1.75-4.11, p < 0.001). Receiving HDLV rescue was associated with a greater likelihood of AKI after MTX (OR = 2.18, 95% CI: 1.38-3.43, p < 0.001). Hospital LOS was longer in those prescribed empiric HDLV rescue after MTX than those prescribed standard leucovorin with an estimated difference of 1.1 days, (95% CI: 0.5-1.7, p < 0.001). CONCLUSION: Sequential HDMTX doses are associated with a significant incidence of elevated MTX levels and AKI during lymphoma management. HDLV rescue prescribed during subsequent MTX doses in patients with a previously elevated level was not associated with improved safety outcomes. The optimal supportive care strategy following HDMTX administration requires further investigation.

Management of chemotherapy-induced alopecia (CIA): A comprehensive review and future directions.

OBJECTIVES: To review and summarize the available literature on the management of chemotherapy-induced alopecia (CIA) including complementary and alternative medicine (CAM), and to present CIA's effect on quality of life (QoL). METHODS: Nine databases were searched for CIA-related keywords, including the effect on QoL, and management options. Among 1019 articles found, 54 articles focusing on treatment/prevention or QoL were retrieved. References of selected articles were also checked manually. RESULTS: CIA was found to negatively affect QoL and body image, regardless of head covering status (i.e., for cultural or religious reasons). Most studies related to treatment/prevention of CIA reported on the use of scalp-cooling. The efficacy of CAM treatments was found to be questionable. CONCLUSION: A high incidence rate of CIA exists with certain chemotherapies, and it significantly impairs QoL. Preventive and treatment strategies are incompletely effective. Additional literature is needed to explore potential preventive or therapeutic options for CIA.

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.

Symptom burden and integrative medicine in cancer survivorship.

PURPOSE: The purpose of the study was to learn about the level of experience with, interest in, and desire for knowledge about integrative medicine (IM) among cancer survivors. METHODS: Cancer survivors attending the 2014 National Cancer Survivors Day in Rochester, MN, were recruited to participate in a one-page survey about their ongoing health concerns and symptoms, as well as their experience with, interest in, and desire for knowledge about IM. Two-sided t test was used for univariate analyses of impact of sex, time since diagnosis, and age. RESULTS: Among the 260 cancer survivors, 171 persons (female, 74 %; male, 26 %) completed the survey (mean age, 64.6 years). Symptoms most commonly somewhat or more bothersome were fear of recurrence (52 %), stress (43 %), fatigue (43 %), difficulty sleeping (33 %), and weight gain (31 %). The most used IM resources were exercise (75 %), improved nutrition and diet (66 %), stress management (42 %), dietary supplementation (33 %), meditation (25 %), and massage (22 %). Older patients (age, ≥65 years) were less experienced with, interested in, and desiring of knowledge about IM techniques. Sex and time since diagnosis were not strongly predictive of most survey response categories. CONCLUSIONS: Cancer survivors have adverse effects for years into survivorship. They use and express interest in various IM techniques to help manage symptoms. It is critical that oncology providers help survivors address ongoing health concerns. Education about and access to evidence-based IM techniques may have important roles in comprehensive cancer survivorship programs.

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.

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.