Andrea Sitlinger

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is the most common incurable leukemia/lymphoma in the United States. Individuals with CLL are at risk for disability, frailty, and cancer-specific complications that negatively affect health-related quality of life (HRQOL). High-intensity interval training (HIIT) and resistance training (RT) are safe and feasible for individuals with chronic diseases and when combined, they may be beneficial for reducing cancer-related fatigue, symptom burden, and global quality of life. However, no studies have examined the impact of HIIT or RT on HRQOL in CLL. The purpose of this study was to investigate the effects of a 12-week HIIT and RT (HIIT+RT) intervention on HRQOL in adults with treatment naïve CLL. MATERIALS AND METHODS: Changes in HRQOL was a secondary outcome in this pilot study. Individuals with CLL (63.9 ± 8.5 yrs) were non-randomly assigned to 12 weeks of HIIT+RT or a control group. The HIIT+RT protocol consisted of three 30-min sessions/week of HIIT and two sessions/week of RT. The control group maintained usual daily activities. We assessed pre and post HRQOL using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire with domains of physical (PWB), social (SWB), emotional (EWB), functional (FWB), and general (FACT-G) well-being as well as a lymphoma-specific subscale (LymS). We used a two-way mixed analysis of variance to assess changes in HRQOL. We calculated effect size (ES) using Cohen's d. RESULTS: Fifteen participants (HIIT+RT: n = 9; Control: n = 6) completed the study and questionnaire. Scores for FWB improved following HIIT+RT (21.7 ± 3.4 to 23.9 ± 3.2; ES = 1.38) compared to controls (25.7 ± 2.2 to 25.7 ± 2.3). The HIIT+RT group experienced clinically meaningful improvements in total FACT-Lym, FWB, FACT-G, and LymS. The control group had clinically meaningful changes only in LymS. DISCUSSION: The large effect sizes and clinically meaningful improvements associated with 12 weeks of HIIT+RT support the potential benefits of this type of exercise program for FWB, lymphoma-specific symptoms, and general well-being in CLL. A future randomized trial with an adequately powered sample size is needed to evaluate these findings. TRIAL REGISTRATION: NCT04950452.

CONTEXT: Ibrutinib and other Bruton-tyrosine kinase inhibitors (BTKi) have transformed treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and improved overall survival. However, cardiovascular and other non-CLL progression related events remain a significant cause of morbidity and mortality for patients with CLL. Therefore, it is important to more fully understand and optimize management of cardiometabolic risk factors such as hypertension. OBJECTIVE: Determine the prevalence of new-onset or uncontrolled hypertension following initiation of ibrutinib and determine whether age is associated is associated with this outcome. DESIGN: Retrospective chart review Setting: Single academic institution Patients: Consecutive CLL/SLL patients (n=219) treated with ibrutinib at Duke University Medical Center from April 18, 2011 through October 31, 2019. MAIN OUTCOME MEASURES: New-onset or uncontrolled hypertension. RESULTS: Prior to initiation of ibrutinib, 130/219 (59.4%) patients had preexisting hypertension (80% controlled, 13.8% uncontrolled, 6.2% indeterminate). Following ibrutinib, 100/130 (76.9%) became uncontrolled. When compared to younger patients, the risk of developing uncontrolled hypertension was lower in those ages 65-74yo (p=.03). The median number of days from ibrutinib initiation to development of uncontrolled hypertension (N=67) was not associated with age (p=0.49). Of the 89 patients without hypertension prior to ibrutinib, 47.2% developed new-onset hypertension. There was no significant difference in incidence of new-onset hypertension by age (42.9%, 57.1%, 42.1% of those <65, 65-74, and 75+ years old, respectively). The median time between ibrutinib initiation and development of new-onset hypertension was not associated with age (p=.34). CONCLUSIONS: Over two-thirds (65%) of CLL/SLL patients developed new-onset or uncontrolled hypertension after starting ibrutinib. Age did not appear to be associated with these changes. The increase in prevalence of hypertension highlights the importance of blood pressure monitoring, irrespective of age, after initiation of ibrutinib.

BACKGROUND: Venous thromboembolism (VTE) affects approximately 1-2 individuals per 1000 annually and is associated with an increased risk for pulmonary hypertension, postthrombotic syndrome, and recurrent VTE. OBJECTIVE: To determine risk factors, incidence, treatments, and outcomes of VTE through a 2-year surveillance program initiated in Durham County, North Carolina (population approximately 280,000 at time of study). PATIENTS/METHODS: We performed a retrospective analysis of data actively collected from three hospitals in Durham County during the surveillance period. RESULTS: A total of 987 patients were diagnosed with VTE, for an annual rate of 1.76 per 1000 individuals. Hospital-associated VTE occurred in 167 hospitalized patients (16.9%) and 271 outpatients who were hospitalized within 90 days of diagnosis (27.5%). Annual incidence was 1.98 per 1000 Black individuals compared to 1.25 per 1000 White individuals (p < 0.0001), and Black individuals with VTE were younger than White individuals (p < 0.0001). Common risk factors included active cancer, prolonged immobility, and obesity, and approximately half were still taking anticoagulant therapy 1 year later. A total of 224 patients died by 1 year (28.5% of patients for whom outcomes could be confirmed), and Black patients were more likely to have recurrent VTE than White patients during the first 6 months following initial presentation (9.4% vs. 4.1%, p = 0.01). CONCLUSIONS: Ongoing surveillance provides an effective strategy to identify patients with VTE and monitor treatment and outcomes. We demonstrated that hospital-associated VTE continues to be a major contributor to the burden of VTE and confirmed the higher incidence of VTE in Black compared to White individuals.

Many patients with chronic lymphocytic leukemia (CLL) experience physical dysfunction and low overall fitness. It remains unknown what factors drive CLL physical dysfunction. We assessed physical function and metabolic lipoprotein panels in 106 patients with CLL. In univariate analyses of clinical factors, a longer time since diagnosis was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 3.56, 95% CI: 1.37-9.22; p = 0.002) and physical performance (SPPB: OR = 2.03, 95% CI: 1.20-3.44; p = 0.004). Having received treatment was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 1.57, 95% CI: 1.02-2.40; p = 0.036), SPPB (OR = 1.85, 95% CI: 1.13-3.03; p = 0.011) and grip strength (OR = 1.67, 95% CI: 1.10-2.55; p = 0.015). We found that several small HDL particle parameters, higher levels of citrate (OR = 2.01, 95% CI: 1.22-3.31; p = 0.030), and lower levels of hemoglobin (OR = 0.50, 95% CI: 0.31-0.82; p = 0.030) were associated with a higher likelihood of dysfunctional aerobic fitness. Multivariable least absolute shrinkage and selection operator (LASSO)-penalized regression analyses using variable importance measures (VIM) showed that 7.8-nm HDL particles (VIM = 1.000) and total HDL particle levels (VIM = 1.000) were more informative than clinical measures for the odds of dysfunctional aerobic fitness and 6-min walk functional fitness, respectively, while 10.3-nm HDL particles (VIM = 0.383) were more informative for grip strength. Time since diagnosis (VIM = 0.680) and having received treatment (VIM = 0.490) were more informative than lipoprotein measures for the odds of having dysfunctional SPPB. Taken together, we establish significant relationships between clinical and metabolic factors and physical characteristics that might prompt early use of ancillary support services.