Comparison of Dietary Intake and Dietary Inflammatory Index in Patients with Chronic Lymphocytic Leukemia By Treatment Status to Cohabitating Controls

Chronic lymphocytic leukemia (CLL) is an incurable disease with a varied presentation ranging from indolent and asymptomatic to morbid and life-limiting. As tumor biology insufficiently explains this variability, we hypothesized that behavioral and environmental factors including diet and the gut microbiome, where diet is a key influence, may influence CLL pathogenesis and response to therapy.

We performed a cross-sectional sample and survey collection study of the gut microbiome, blood, and diet in patients with CLL treated at the University of Nebraska Medical Center between 2021-2023. Eligible subjects included 1) untreated CLL with Rai stage 2-4 disease (untreated CLL), 2) CLL treated with a Bruton's tyrosine kinase inhibitor (BTKi), and 3) individuals without cancer cohabitating with enrolled CLL subjects (control). All subjects provided stool samples for microbial analysis, and subjects with CLL provided blood for serum cytokine analysis. All subjects completed the Diet History Questionnaire version 3.0 (DHQ-3). The DHQ-3 is a self-administered food frequency questionnaire, where participants complete 135 questions on food/beverages and 26 on dietary supplements consumed in the past month. A total and component healthy eating index (HEI) score was derived from the DHQ-3 and represents how well diet intake corresponds to the dietary guidelines recommended by the United States Department of Agriculture and Health and Human Services. The HEI is based on 13 individual components (Figure 1) and scored from 0-100, where higher scores indicate healthier diets. Inflammatory capacity of the diet was assessed by the Dietary Inflammatory Index (DII) (Shivappa et al, Public Health Nutrition, 2013), a measure of dietary components associated with serum markers of inflammation. The DII has a range of scores up to 7.98 suggestive of greater systemic inflammation (median DII score 0.23), and a minimum of -8.87, suggestive of consumption of anti-inflammatory foods. The DII was calculated and compared between each cohort. Statistical analysis was performed using ANOVA.

A total of 58 subjects enrolled on the study, 42 with CLL and 16 cohabitating controls. A total of 27 subjects were included in the analysis after data cleaning. Fifteen subjects (56%) were treated with a BTKi, 5 (19%) had untreated Rai stage 2 disease, and 7 (26%) were cohabitating controls. Median ages (72 vs 67 vs 71 for BTKi, untreated, control, respectively) were similar. Median absolute lymphocyte count was 3.2 cells x10^3/µL (1.3 - 131 range) in the BTKi and 55 cells x10^3/µL (13-134 range) in the untreated cohort. There were 5/15 (33%) with 17p deletion and/or p53 mutation in the BTKi cohort and 2/5 (40%) in the untreated cohort. Median time from diagnosis to study entry was 30 months (range 3-151 months) in the untreated cohort, and median time on BTKi therapy was 30 months (range 2-92 months). Within the BTKi cohort, 33% received ibrutinib, 20% received zanubrutinib, and 47% received acalabrutinib. Overall dietary habits were largely similar between the 3 cohorts (Table 1). The mean total HEI score was higher in the untreated (66) and control (66) populations compared to the BTKi cohort (59) ( p = 0.23), although not significantly different. These scores are similar to the 2020 median score of 61 for Americans 60 years and above. Added sugar intake was highest in the untreated cohort (HEI component score of 9.6, 6.3, 8.6 untreated, BTKi, control p = 0.005, respectively) (Figure 1).

After calculating the DII for each cohort, no statistically significant differences were observed (Table 1). The range of DII scores across subjects was -5.2 - 4.0, within the expected range for DII calculations. DII scores were 0.44, 0.2, 0.82 p = 0.89 for BTKI, untreated CLL, and control cohorts respectively.

To our knowledge, this study is the first to analyze dietary patterns in well-defined homogenous CLL populations (BTKi vs Rai stage 2+ CLL cohort) and compare them to cohabitating individuals. Although overall dietary patterns and DII were similar across cohorts, slight differences in added sugar intake was observed between the cohorts, suggestive that subtle yet important dietary differences may be observed. These data provide a baseline to study personalize dietary approaches to patients with CLL, who increasingly ask clinicians for nutritional interventions as part of their comprehensive cancer care.