Frankie F. Brown ^1,2* Rebecca Oliver ^1,3 Rachel Eddy ¹ Adam J. Causer ¹ Annabelle Emery ¹ Harrison D. Collier-Bain ¹ David Dutton ⁴ Josephine Crowe ³ Daniel Augustine ⁵ John Graby ⁵ Daniel Rees ¹ Daniela Rothschild Rodriguez ⁶ Oliver J. Peacock ¹ Sally Moore ³ James Murray ³ James E. Turner ^1,7 John P. Campbell ^1,8*

• ¹ University of Bath, Bath, United Kingdom
• ² School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom
• ³ Department for Haematology, Royal United Hospital Bath NHS Trust, Bath, Surrey, United Kingdom
• ⁴ Great Western Hospitals NHS Foundation Trust, Swindon, United Kingdom
• ⁵ Department for Cardiology, Royal United Hospital Bath NHS Trust, Bath, Somerset, United Kingdom
• ⁶ School of Biological Sciences, University of Southampton, United Kingdom., Southampton, United Kingdom
• ⁷ School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom., Birmingham, United Kingdom
• ⁸ School of Medical and Health Sciences, Edith Cowan University, Cowan, Western Australia, Australia

Background: Chronic lymphocytic leukaemia (CLL) typically presents with asymptomatic, early-stage disease that is monitored until disease progression ("treatment-naïve" CLL). The objective of this pilot study was to assess the feasibility and preliminary safety of an exercise program in treatment-naïve CLL. We also sought to preliminarily assess the impact of the exercise program on disease activity, as it has been proposed that exercise training may reduce disease outgrowth in treatment-naïve CLL.Methods: Forty treatment-naïve CLL patients were recruited into this randomised-controlled pilot study, and after screening, n=28 were randomised into a 16-week, home-based, partially supervised, personalised, progressive exercise intervention (n=14: mean ± SD: age=62 ± 12 years) or 16-weeks of usual care, control group (n=14: mean ± SD: age=61 ± 10 years). The primary outcome measures were safety (number and severity of adverse events) and feasibility (uptake, retention, and adherence to the trial). Disease activity (CD5+/CD19+ CLL cells clonally restricted to kappa or lambda) and other immune cell phenotypes, with a principal focus on T cells, were measured by flow cytometry. Other secondary outcomes included: DEXA derived body composition, cardiorespiratory and functional fitness, resting cardiovascular measures.Results: Trial uptake was 40%, the overall retention rate was 86%, with 79% of the exercise group and 93% of the control group completing the trial. Adherence to the exercise intervention was 92±8%. One serious adverse event was reported unrelated to the trial, and one adverse event related to the trial was reported. The exercise intervention elicited a 2% increase in DEXA-derived lean mass in the exercise group compared to a 0.4% decrease in the control group (p=0.01). No between group differences were observed over time for whole-body mass, BMI, bone mineral density, body fat, blood pressure resting heart rate, or measures of cardiorespiratory or functional fitness (all p>0.05). No between group differences were observed over time for clonal CLL cells, CD4+ or CD8+ T cell subsets (all p>0.05). The exercise training program used in this study was feasible in people with treatment-naïve CLL who passed pre-trial screening, and we preliminarily conclude the exercise training program was safe and also resulted in an increase in lean mass.