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Written by Jennifer Mercer,  supported by Janet Baker

Physical activity (PA) is defined as any skeletal muscle movement that requires energy (World Health Organisation, 2019). Whilst patients are undergoing treatment for haematological malignancies (HM), PA may reduce dramatically.  Due to treatment side effects such as nausea/vomiting, cancer-related fatigue (CRF) and mucositis, a majority of patients will spend a large percentage of their day in an inactive state.  In addition, due to neutropenia/risk of infection, patients may be in protective isolation, further restricting PA (Annibali et al., 2017).  

 
Whilst HM can affect people of all ages, they mainly occur within the elderly population, with a mean age of 70.6 years (Li et al., 2016).  Consequently, at diagnosis, individuals may present with numerous co-morbidities. For example, 40% of individuals with Chronic Lymphocytic Leukaemia (CLL) have osteoarthritis, high cholesterol and hypertension (Strati et al., 2017).  Additionally, Multiple Myeloma (MM) patients, with a median age of 69, often have a history of cardiovascular disease and renal impairment (Hari et al., 2017).  Such co-morbidities affect a person’s ability to carry out everyday tasks (Sarfati and Koczwara, 2016).  Therefore, these co-morbidities, combined with HM treatment, may have a detrimental effect on a person’s PA whilst in hospital.  
 
Systematic anti-cancer therapy is often the first line of treatment (Haematological Malignancy Research Network, 2014).  However, side effects include weight loss due to changes in appetite, nausea and vomiting, CRF, affecting 70% of patients, and neutropenia, resulting in the need for protective isolation due to the risk of infection (Cancer Research UK, 2017; Macmillan Cancer Support, 2018).  Combined, these contribute to a loss of muscle mass, functional decline and a possible reduction in the intensity of future treatments (Duregon et al., 2019; Klepin et al., 2016).  
 
The frailty cycle is a deconditioning syndrome in which the reduction of muscle mass leads to reduced strength, a consequent decline in PA, and increased fatigue, all of which lead to decreased functional ability, further exacerbating muscle loss (Hacker et al., 2017).  This vicious cycle can be found in the HM population (Koll and Rosko, 2018).  It has been argued that PA, before, during and after treatment, can improve physical functioning/fitness, and impact on CRF (Campbell et al., 2019; Cha et al., 2018; Hacker et al., 2017).  
 
Whilst PA guidelines for the older adult population are clear – 75 to 150 minutes of PA per week (Department of Health and Social Care, 2019) – recommendations for the haemato-oncology population remain vague (Knips et al., 2019).   Campbell et al. (2019) advises that exercise is safe for the cancer survivor population and that previous medical advice to rest and avoid exercise is no longer applicable (Knips et al., 2019).  
 
Deconditioning is the process of physiological change, primarily muscular, following prolonged inactivity (Ploutz-Snyder et al., 2018).  Deconditioning has been linked to increased risk of falls, functional decline and immobility (Arora, 2017).   Furthermore, the loss of skeletal muscle due to inactivity during treatment, has been linked to increased levels of CRF (LaVoy, Fagundes and Dantzer, 2016).  During HM treatment, physical functioning declines rapidly, and recovery to baseline, once treatment is complete, can be slow (Bewarder et al., 2019). 
 
Cha et al. (2018) investigated an inpatient rehabilitation programme on recovery from deconditioning in individuals undergoing treatment for HM which found statistically significant functional improvement after rehabilitation. This was particularly evident in MM patients.  Within the MM group, the body mass index (BMI) was higher, an average of 23.7.  An average BMI of 23.7 is at the upper end of what is classed as a healthy BMI (18.5-24.9) (National Health Service, 2019).  Individuals with a higher BMI experience less toxicity than those with a lower or normal BMI, a protective effect known as the “Obesity Paradox” (Morrison et al., 2019; Shachar and Williams, 2017).  Therefore, it could be argued that, due to the higher BMI of the MM sample, they may have experienced reduced toxicity and, as a result, were then able to partake in a more intensive exercise session, resulting in reduced deconditioning.   Therefore, if PA enables patients to maintain/increase their BMI whist undergoing treatment, arguably this could counteract side effects and prevent deconditioning.  However, a limitation of the Cha et al. (2018) study is the participants’ mean age of 53.9 years.  As previously mentioned, the average age of individuals with an HM is 70.6 years. Therefore, these findings may not be transferable to the general HM population.  By not including older HM patients within such studies, it could be argued that clinicians can only estimate the benefits/risk of PA. 
 
In two larger single-blind randomised control trials (RCT), both focusing on individuals undergoing stem cell transplant (SCT) for HM, Hacker et al. (2017) investigated strength training, whilst Persoon et al. (2017) looked at a high intensity exercise programme.  Hacker et al. (2017) explored PA, CRF, functional ability, muscle strength and quality of life in a programme beginning immediately after the SCT (67 participants), whilst Persoon et al. (2017) began their PA programme 6-14 weeks after SCT (109 participants).  Hacker et al. (2017) found that the Interventional Group experienced improvements in PA, fatigue, walk time and arm strength. However, not all results were statistically significant.  Persoon et al. (2017) found that physical fitness and fatigue improved in both groups, but the results were also statistically non-significant.  A possible reason for this may be the timing of the intervention, as Liang et al. (2018) found that deconditioning and CRF primarily occurs in the period immediately following HM treatment.  Therefore, it could be said that the timing of a PA intervention is key when aiming to prevent deconditioning and fatigue. 
 
Cancer-related fatigue, defined as ‘a subjective unrelenting sense of physical, emotional and mental exhaustion’ as a result of treatment or the cancer itself, can hinder/restrict activities associated with daily living (National Comprehensive Cancer Network, 2018. Page FT1).  Exercise and CRF in breast cancer has been widely researched, and PA has been found to reduce CRF by counteracting low-grade inflammatory cytokines such as interleukin 6 (Meneses-Echavez et al., 2016), which is also found in HM patients undergoing treatment (Burger, 2013).  Solid tumours and HM have very different trajectories (Chan and Chan, 2015).  However, these findings could be transferable as it was found that interleukin 6 correlates to fatigue in the HM population (Khosravi et al., 2018).  However, in a larger study by Alibhai et al. (2019), inflammatory cytokines could only be held accountable for a small percentage of CRF in HM.  Despite this, this study highlighted that interventions such as exercise may still be valuable in reducing cytokine-induced CRF.  However, HM treatment tends to be more intensive and longer in duration (Minton, Foster and Maher, 2015), therefore the level of cytokines, and subsequent CRF, may be more significant and harder to resolve.  
 
It is proposed that the creation of exercise-prompt posters, an example of which can be seen in Appendix 1, would help to promote in-patient exercise opportunities that would contribute to the patient’s overall health and, possibly, promote long-term behavioural changes.  Bellettiere et al. (2018) investigated the use of sign prompts, encouraging individuals to use the stairs/climb an escalator, rather than passively using an escalator.  Within this study, poster prompts increased stair use by 115% when compared to escalator use, highlighting the effectiveness of point-of-choice prompts.  These posters would be placed at “points-of-choice” such as at a windowsill prompting patients to march on the spot, in front of the bed where they could do arm/leg raises whilst in bed, or near to a chair where they could do standing up/sitting down exercises.    
 
During hospital admission, patients can become very reliant on nurses in relation to daily living activities (Sung and Herbst, 2017).  Encouraging patients to engage in PA could promote independence and contribute to a safe discharge (Clarke, Stack and Martin, 2017).  Consequently, by empowering patients to take ownership of their own body maintenance through poster prompts, it could be argued that this could promote independence on the part of the patient and make their transition from inpatient to outpatient easier.  
 
However, as seen in home exercise programmes where responsibility falls to the individual, non-adherence can be as high as 50% (Argent, Daly and Caulfield, 2018). Therefore, when combined with treatment side effects, inpatient adherence may be similar, or worse.  In an RCT investigating exercise telephone counselling in HM, exercise adherence was 93%, highlighting the importance of clinician involvement/encouragement (Vallerand et al., 2018).  The success of any intervention depends on adherence, and the clinician’s recognition that non-adherence does occur (Argent, Daly and Caulfield, 2018).  Health care professionals (HCP) are in a prime position to encourage and promote inpatient PA.  However, a lack of HCP knowledge, a fear of patient falls, and the “rest and recuperate” ideology, can prevent the promotion of PA (Blackburn et al., 2016; Knips et al., 2019).  Through effective education, HCP’s could be made aware that resting actually exacerbates fatigue (Knips et al., 2019) and that exercise can, in fact, reduce falls (Hill et al., 2015).  In this way, HCP can have a key role in encouraging PA.  
 
To conclude, haematological malignancies occur mainly in the elderly population.  Physical activity in the HM population has been deemed safe and can prevent deconditioning and improve CRF.  However, treatment has a high symptom burden which can contribute to deconditioning and CRF.  It has been found that PA before, during and after HM treatment can have a positive effect on deconditioning and reduce CRF.  Point-of-choice prompts have been found to increase PA.  Therefore, through the development of PA posters, it is hoped that this will encourage, empower and motivate patients to undertake PA during their inpatient stay.  However, recognition that adherence may be poor, highlights the importance of HCP involvement in PA promotion.  Therefore, it is hoped that inpatient PA promotion can prevent deconditioning and reduce CRF, thereby improving patient outcomes.     
 
 

References

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Annibali, O., Pensieri, C., Tomarchio, V., Biagioli, V., Pennacchini, M., Tendas, A., Tambone, V., and Tirindelli, M.C. (2017) ‘Protective Isolation for Patients with Haematological Malignancies: A Pilot Study Investigating Patients’ Distress and Use of Time’, International Journal of Hematology-Oncology and Stem Cell Research, 11(4), pp.313-318.  
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Bellettiere, J. Nguyen, B., Liles, S., Berardi, V., Adams, M.A., Dempsey, P., Benporat, Y., Kerr, J., LaCroix, A.Z., and Hovell, M. (2018) ‘Prompts to Increase Physical Activity at Points-of-Choice between Stairs and Escalators: What about Escalator Climbers?’, Translational Behavioural Medicine, 9, pp.656-662. 

Bewarder, M., Klostermann, A., Ahlgrimm, M., Bittenbring, J.T., Pfreundschuh, M. Wagenpfeil, S., and Kaddu-Mulindwa, D. (2019) ‘Safety and Feasibility of Electrical Muscle Stimulation in Patients Undergoing’, Supportive Care in Cancer, 27(3), pp.1013-1020.  

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The impact of physical activity on deconditioning and cancer-related fatigue in the haemato-oncology population. | The Royal Marsden School
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