Mobilising tumour and immune cells via exercise in CLL
Research type
Research Study
Full title
Characterising tumour and immune cell mobilisation into blood in response to acute exercise in chronic lymphocytic leukaemia.
IRAS ID
272493
Contact name
John Campbell
Contact email
Sponsor organisation
University of Bath
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 5 months, 31 days
Research summary
Research Summary
Chronic lymphocytic leukaemia (CLL) is the most common adult blood cancer in the UK. CLL means that many cancer cells appear in the blood, bone marrow and other tissues, for example, the spleen where some blood cells are stored. Most patients with CLL have been diagnosed by chance, have no symptoms as a result of CLL, and do not need urgent treatment. However, when the cancer cells build up, people experience symptoms of CLL, and treatment is required. One of the current treatments for CLL is chemo-immunotherapy, that targets and kills cancer cells in the blood. However, this treatment does not kill all cancer cells. Some cancer cells survive by ‘hiding’ in the bone marrow and tissues, like the spleen, where the treatment cannot get to, this is called minimal residual disease (MRD). MRD eventually builds up and patients experience symptoms of CLL again. New approaches to detect and treat MRD are needed. Research has shown, that the number of blood cells, increases after exercise and that many of these blood cells come from the bone marrow and other tissues. This study will investigate if exercise can move CLL cancer cells that are ‘hiding’ in the bone marrow and other tissues into the blood, thus improving the detection of MRD. By moving cancer cells into blood, we also think this will improve the way chemo-immunotherapy works. In this study, we will investigate the number of cancer cells in the blood after exercise, in three different groups of people with CLL: before treatment; during treatment; and after treatment has finished. Participants will be recruited at the Royal United Hospital, Bath (RUH). Participants taking part during treatment, will complete an exercise trial at the RUH, participants taking part before and after treatment, will complete an exercise trial at the University of Bath.
Summary of Results
24 patients with treatment naïve chronic lymphocytic leukaemia (CLL) and 8 patients in CLL remission were recruited for this study. Patients with treatment naïve CLL have a detectable level of cancer in the body but do not experience symptoms of the disease requiring treatment. Therefore, these patients are monitored without treatment until disease progression occurs. Exercise trials and study measurements took place at the University of Bath, United Kingdom. The first exercise trial consisted of a short cycling session on a stationary upright bike which got progressively harder every minute. This test was used to determine the fitness status of participants who took part of the study. The second exercise trial consisted of one 30-minute session of cycling on a stationary upright bike at a moderate intensity. This intensity was determined based on the results from the first exercise trial. Of the 24 patients recruited with treatment naïve CLL, 20 completed all experimental procedures. Of the 8 patients recruited in CLL remission, 3 completed all experimental procedures. Patients who did not complete all experimental procedures were excluded following health screening.
We used blood samples collected before exercise, immediately after exercise, and 1-hour after exercise to examine any changes to the number of immune cells, and the function of immune cells in response to one session of exercise. Immune cell subsets including natural killer cells, monocytes, and B-cells were significantly elevated immediately after one session of moderate intensity exercise, and returned to baseline levels 1-hour following exercise. There was also a significant elevation of CLL cells (a cancerous mature B-cell) immediately following exercise, which returned to baseline levels 1-hour after exercise. Using experiments set-up in our laboratory we found that the increase in natural killer cells resulted in a significant improvement to the effects of an immunotherapy drug called rituximab. Rituximab is used to treat CLL and works by harnessing the human body’s immune system (e.g., natural killer cells) to eliminate cancer cells in the body. These findings are relevant to patients with CLL receiving rituximab therapy because they show that exercise may benefit this treatment by increasing the number of natural killer cells and CLL cells into the blood where rituximab is administered during therapy. Future research should investigate whether sessions of moderate intensity exercise enhance treatment outcomes in symptomatic CLL patients receiving rituximab, as well as other immunotherapies which work through similar processes, such as obinutuzumab. Further information is available on request by contacting Harrison Collier-Bain (hdcb20@bath.ac.uk).REC name
West of Scotland REC 4
REC reference
20/WS/0049
Date of REC Opinion
27 May 2020
REC opinion
Further Information Favourable Opinion