Exercise as it relates to Disease/Exercise and its effects on improving quality of life in Leukemia patients undergoing chemotherapy

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Study- A phase II exercise randomized controlled trial for patients with acute myeloid leukemia undergoing induction chemotherapy[1]

What is the background to this research?[edit]

Acute myeloid leukemia (AML) is a malignant blood disorder in which the affected individual experiences an increased number of immature myeloid cells in bone marrow and other tissues.This causes overcrowding within marrow and causes normal cell production and function to cease. This results in large numbers of abnormal cells to enter the bloodstream.[2]Diagnosis rates In Australia are low with 900 people diagnosed annually, this has resulted in AML being classified as a rare cancer as it accounts for 0.8% of all cancers diagnosed. AML is common in older adults over 60 years of age and in males.[3]

Previous studies have explored the effects of exercise upon AML patients and contain smaller numbers of participants, younger patients and rarely have been randomised trials. These past studies found improvements in self-reported fitness outcomes and were unsuccessful in finding definite evidence that exercise can increase quality of life.[4] AML requires intensive bouts of chemotherapy to cure the disease. The first stage of chemotherapy is the induction phase (IC). This phase lasts 4-6 weeks and aims to achieve remission.[5]During induction chemotherapy- quality of life, fatigue levels, emotional functioning and physical capabilities are all negatively affected.[6]

Where is the research from?[edit]

This study was conducted between June 2011 and February 2013 at the Princess Margaret Cancer Centre in Toronto, Canada. The study was approved by the Institutional Research and Ethics board of Canada. This may relate to Australian populations as both Canada and Australia are 1st world Commonwealth countries. The World Health Organisation recognized in 2016 that Canada and Australia had similar life expectancies, gross national income per capita, total expenditure on health per capita and total expenditure on health as a percentage of gross domestic product.[7][8]This study will not relate to the indigenous Aboriginal and Torres Strait Islander population of Australia.

Shabbir Alibhai lead the study, he is the senior scientist at the Toronto general hospital research institute. His research is focused around cancer in older adults, predominately prostate and acute myeloid leukemia. Many of his major projects involve improving physical function and exercise involvement in cancer patients.[9]The study was published in the Leukemia Research Journal in August 2015.

What kind of research was this?[edit]

A phase 2 randomised control trial was utilised as the study design. A phase 2 randomised control trial focuses on improving previously hypothesised intervention and conclusions and are favoured in oncology studies and research. A phase 1 will commonly assess the safety of an intervention, the phase 2 will assess the effectiveness of an intervention. Further information and conclusions can be drawn from taking another step towards starting a phase 3 trial at the completion of the phase 2.[10] Randomised control trials aim to assess the safety and efficacy of treatments and interventions. With correct planning, execution and analysis, this type of study is considered effective.[11]

What did the research involve?[edit]

Using a 2:1 ratio, the exercise group contained 40 participants and the control, 20. The study’s primary objective was to measure the effect exercise has on quality of life, fatigue and a 6-minute walk test using a variety of measures taken within 7 days of the start of induction chemotherapy, post induction and post cycle 2 of chemotherapy. Methods of measurements were;

  • Quality of life-self reported European organisation for research and treatment of cancer questionnaire (EORTC)
  • Fatigue- self reported functional assessment of cancer therapy fatigue (FACT-F)
  • 6-minute walk test- distance covered in feet

The secondary objective was to increase treatment tolerability, which was monitored using time spent in admission, instances of sepsis and time in ICU as measures. The exercise intervention consisted of an individualised, supervised mixed modality exercise program. Sessions were completed 4-5 days per week, consisted of 30-60 minutes and included a combination of aerobic, resistance, and flexibility training. The exercise program was developed by a certified exercise physiologist and all exercise was monitored using an RPE scale. Patient adherence was monitored, and logs were kept for all reasons for non-participation in exercise. Control group participants were encouraged to walk on a regular basis and all physical activity by the participants was recorded.

What were the basic results?[edit]

The intervention and control group both experienced very small improvements in QOL from baseline to post IC. The intervention group increased the FACT-F scores by a small amount. Both groups increased the 6-minute walk test, with the intervention group possessing a larger improvement yet was deemed statistically insignificant. Anxiety and depression self-reported measures improved in small amounts in the intervention group. Perhaps the most prominent result drawn from this study was treatment tolerability, notably regarding instances of sepsis. A 16.7% drop was recorded across both groups. The study results seemed realistic and were not exaggerated when displaying and discussing results. Perhaps the results of the study seemed un expected and somewhat underwhelming in places yet promising in some.

What conclusions can we take from this research?[edit]

In all, the study analysed seemed well structured and hypothesized, yet a variety of problems were experienced throughout. Adherence in total was at 54%. The extremely demanding and draining process of chemotherapy certainly decreased adherence rates as many participants were commonly too ill or fatigued to take part in any exercise. A variety of self-reported measures were utilised, these are known to either be under or over exaggerated.[12] The participant size of this study was quite small and with larger numbers, improvements in areas such as quality of life will become more statistically significant and provide more impressive results. Further studies into this field of oncology research are needed that display high adherence rates, a large participant number and more statistically significant results are needed before a true place for exercise in improving physical and mental health in chemotherapy patients can be found.

Practical advice[edit]

Research into improving the overall health and quality of life in chemotherapy patients will continue to reach new heights. It can be very controversial and difficult to improve the physical activity levels of chemotherapy patients such as shown in this study. Therefore, it is imperative that exercise physiologists and oncologists continue to work hand in hand to develop a safe and effective physical activity routine that will warrant improvements within the overall health from both self reported and direct measures, of those undergoing chemotherapy.

Further reading[edit]

https://www.journals.elsevier.com/leukemia-research https://www.leukaemia.org.au/acute-myeloid-leukaemia

References[edit]

  1. Alibhai S, Durbano S, Breunis H, Brandwein J, Timilshina N, Tomlinson G et al. A phase II exercise randomized controlled trial for patients with acute myeloid leukemia undergoing induction chemotherapy. Leukemia Research. 2015;39(11):1178-1186.
  2. Döhner H, Weisdorf D, Bloomfield C. Acute Myeloid Leukemia. New England Journal of Medicine. 2015;373(12):1136-1152.
  3. Acute myeloid leukaemia (AML) [Internet]. Leukaemia Foundation. 2018. https://www.leukaemia.org.au/disease-information/leukaemias/acute-myeloid-leukaemia/
  4. Schumacher A, Kessler T, Büchner T, Wewers D, van de Loo J. Quality of life in adult patients with acute myeloid leukemia receiving intensive and prolonged chemotherapy – a longitudinal study. Leukemia. 1998;12(4):586-592.
  5. Dohner H, Estey E, Amadori S, Appelbaum F, Buchner T, Burnett A et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2009;115(3):453-474.
  6. Schumacher A, Wewers D, Heinecke A, Sauerland C, Koch O, van de Loo J et al. Fatigue as an important aspect of quality of life in patients with acute myeloid leukemia. Leukemia Research. 2002;26(4):355-362.
  7. Canada [Internet]. World Health Organization. 2018. http://www.who.int/countries/can/en/
  8. Australia [Internet]. World Health Organization. 2018. http://www.who.int/countries/aus/en/
  9. Shabbir Alibhai | UHN Research [Internet]. Uhnresearch.ca. 2018. http://www.uhnresearch.ca/researcher/shabbir-alibhai
  10. Mandrekar S, Sargent D. Randomized Phase II Trials: Time for a New Era in Clinical Trial Design. Journal of Thoracic Oncology. 2010;5(7):932-934.
  11. Kabisch M, Ruckes C, Seibert-Grafe M, Blettner M. Randomized Controlled Trials. Deutsches Aerzteblatt Online. 2011;108(39):663-668.
  12. Bhandari A, Wagner T. Self-Reported Utilization of Health Care Services: Improving Measurement and Accuracy. Medical Care Research and Review. 2006;63(2):217-235.