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The Effectiveness of Exercise in Treating Childhood Leukemia

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Introduction

Leukemia is a cancer that affects bone marrow and damages the formation of blood cells, and it is the most common childhood cancer and accounts for 30% of all childhood malignancies (Amitay & Keinan-Boker, 2015). While there are several forms of childhood leukemia, acute lymphoblastic leukemia (ALL) is the most common and accounts for 26% of all childhood cancers (San Juan et al., 2007). There are approximately 3,000 children and young adults diagnosed with ALL yearly in the United States (Children’s Hospital of Philadelphia 2019). Due to treatment improvements over the past decades, the cure rate is now at 70%, which has lead to a new awareness of the adverse effects associated with treatment (i.e., quality of life (QOL) and functional capacity) (Lucia, Ramirez, San Juan, Fleck, Garcia-Castro & Madero, 2005). Exercise has been shown to be a valuable tool for adults with and survivors of cancer, with additional research starting to look into the effect of exercise and children with cancer (Gocha Marchese, Chiarello & Lange, 2003; Lucía, Earnest & Pérez, 2003; Marchese, Chiarello & Lange, 2004). Therefore, the purpose of this brief review is to describe the role of aerobic and anaerobic exercise on improving the mortality, recurrence, and treatment-related adverse effects of childhood leukemia.

Mortality

Chemotherapy, radiation, and other methods of treatment have increased the survival rate of ALL to ~70% (Lucia, Ramirez, San Juan, Fleck, Garcia-Castro & Madero, 2005). Due to the aggressive protocol, 98% of patients diagnosed with ALL go into remission within weeks of the beginning of treatment. There is little research into how exercise impacts mortality and recurrence rates in ALL, however exercise has been shown to prevent or decrease the severity of the adverse effects of treatment (e.g., deconditioning, muscle weakness, reduced QOL). Although the survival rate of ALL is relatively high, the long-term effects of treatment may be detrimental. A 25 year follow up found that survivors were more likely to report poor general health and cardiovascular related ailments (e.g., congestive heart failure, coronary artery disease, myocardial infarction, cardiac arrest) (Mody et al, 2008). A well-regulated exercise program may prevent the onset of cardiovascular related illnesses.

Recurrence

The initial remission rate for ALL is promising, however approximately ⅓ of standard-risk and ⅔ of high-risk patients will have disease recurrence (Oriol et al., 2010). Approximately 90% of individuals afflicted will be “cured” of the disease, however cured is defined as spending 10 years in remission (St. Jude Children’s Research Hospital 2019). Previous research has indicated that a relapse can occur later in life (~30 years old), so even if a patient is deemed cured there is still a possibility of recurrence (Oriol et al., 2010). There are conflicting data in regard to recurrence, however the minimum reported is that approximately 15-20% of individuals who go into complete remission will have the disease resurface later in life (Dana Farber Cancer Institute 2019). To the researchers’ knowledge, there have been no studies documenting the effects of exercise on recurrence rates of ALL. However, as with mortality rates, exercise may lessen the adverse effects of treatments (e.g., fatigue, muscle weakness, deconditioning, QOL).

Treatment-Related Adverse Effects

Some of the factors leading to the decrease in QOL and functional capacity following treatment include muscle weakness, lowered aerobic capacity, fatigue, reduced ankle range of motion, osteopenia and osteoporosis, weight changes, depression, and pain (Burnham & Wilcox, 2002; Lucia, Ramirez, San Juan, Fleck, Garcia-Castro & Madero, 2005). Additionally, children that receive a bone marrow transplant typically experience severe physical deconditioning and muscle weakness, due to the intensive corticosteroid treatment following surgery (van Brussel, Takken, Lucia, van der Net & Helders, 2005). However, exercise has been shown to increase functional capacity and aerobic capacity in both children and adult cancer patients and survivors, which in turn leads to improvements in QOL (Lucía, Earnest & Pérez, 2003; Lucia, Ramirez, San Juan, Fleck, Garcia-Castro & Madero, 2005; Marchese, Chiarello & Lange, 2004; San Juan et al, 2007). A study examining the effect of 4-months of physical therapy and home based aerobic, resistance, and flexibility training on children (age 4-18 years) receiving treatment for ALL found improvements in both ankle range of motion and knee extension strength, ultimately leading to improvements in gait (Marchese, Chiarello & Lange, 2004). Additionally, another study found that 16 weeks of resistance (one set of 8-15 repetitions of 11 exercises) and aerobic training (30 minutes at >70% HRmax) was able to improve upper and lower body muscular strength, VO2peak, ventilatory threshold, and functional mobility test times (timed stair climbing, and timed 3-m and 10-m up and go) in a group of 4-7 year olds with ALL (San Juan et al, 2007). Additionally, the majority of improvements in muscular strength and functional mobility were maintained following 20-weeks of detraining, while the improvements in VO2peak and ventilatory threshold were partially maintained (San Juan et al, 2007). Furthermore, while studies have not examined the effect of exercise and the psychological health of patients and survivors of ALL, previous literature has shown that exercise can improve psychological health in survivors of other cancers (Burnham & Wilcox, 2002; Galvão & Newton, 2005; Saxton et al, 2014).

Conclusion

ALL is the most common form of childhood leukemia, with roughly 3000 children and adults being diagnosed with ALL every year in the US. Due to improvements in the treatment, the survival rate is now at ~70%, which has led to a new awareness in approving the adverse effects of treatment. Exercise has been shown to improve both the quality of life and functional capacity of patients and survivors of ALL and other forms of cancer. While research has not looked at the effect of exercise on the mortality and recurrence of ALL, exercise should be considered as an important modality treatment to improve the treatment-related adverse effects of ALL.

References

  • Amitay, E. L., & Keinan-Boker, L. (2015). Breastfeeding and childhood leukemia incidence: a meta-analysis and systematic review. JAMA Pediatrics, 169(6), e151025-e151025.
  • Burnham, T. R., & Wilcox, A. (2002). Effects of exercise on physiological and psychological variables in cancer survivors. Medicine and Science in Sports and Exercise, 34(12), 1863-1867.
  • Children’s Hospital of Philadelphia (2019). Acute Lymphoblastic Leukemia (ALL). (n.d.). Retrieved from https://www.chop.edu/conditions-diseases/acute-lymphoblastic-leukemia-all
  • Dana Farber Cancer Institute (2019). Relapsed Acute Lymphoblastic Leukemia. (n.d.). Retrieved from http://www.danafarberbostonchildrens.org/conditions/leukemia-and-lymphoma/relapsed-acute-lymphoblastic-leukemia.aspx
  • Galvão, D. A., & Newton, R. U. (2005). Review of exercise intervention studies in cancer patients. Journal of clinical oncology, 23(4), 899-909.
  • Gocha Marchese, V., Chiarello, L. A., & Lange, B. J. (2003). Strength and functional mobility in children with acute lymphoblastic leukemia. Medical and Pediatric Oncology: The Official Journal of SIOP—International Society of Pediatric Oncology (Societé Internationale d’Oncologie Pédiatrique, 40(4), 230-232.
  • Järvelä, L. S., Kemppainen, J., Niinikoski, H., Hannukainen, J. C., Lähteenmäki, P. M., Kapanen, J., … & Heinonen, O. J. (2012). Effects of a home‐based exercise program on metabolic risk factors and fitness in long‐term survivors of childhood acute lymphoblastic leukemia. Pediatric Blood & Cancer, 59(1), 155-160.
  • Lucía, A., Earnest, C., & Pérez, M. (2003). Cancer–related fatigue: can exercise physiology assist oncologists?. The Lancet Oncology, 4(10), 616-625.
  • Lucia, A., Ramirez, M., San Juan, A. F., Fleck, S. J., Garcia-Castro, J., & Madero, L. (2005). Intrahospital supervised exercise training: a complementary tool in the therapeutic armamentarium against childhood leukemia. Leukemia, 19(8), 1334.
  • Marchese, V. G., Chiarello, L. A., & Lange, B. J. (2004). Effects of physical therapy intervention for children with acute lymphoblastic leukemia. Pediatric Blood & Cancer, 42(2), 127-133.
  • Mody, R., Li, S., Dover, D. C., Sallan, S., Leisenring, W., Oeffinger, K. C., … & Neglia, J. P. (2008). Twenty-five–year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Blood, 111(12), 5515-5523.
  • Oriol, A., Vives, S., Hernández-Rivas, J. M., Tormo, M., Heras, I., Rivas, C., … & del Potro, E. (2010). Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. Haematologica, 95(4), 589-596.
  • San Juan, A. F., Fleck, S. J., Chamorro-Viña, C., & Maté-Muñoz, J. L. (2007). Early-phase adaptations to intrahospital training in strength and functional mobility of children with leukemia. Journal of Strength and Conditioning Research, 21(1), 173.
  • San Juan, A. F., Fleck, S. J., Chamorro-Viña, C., Maté-Muñoz, J. L., Moral, S., PERez, M., … & Madero, L. (2007). Effects of an intrahospital exercise program intervention for children with leukemia. Medicine & Science in Sports & Exercise, 39(1), 13-21.
  • Saxton, J. M., Scott, E. J., Daley, A. J., Woodroofe, M. N., Mutrie, N., Crank, H., … & Coleman, R. E. (2014). Effects of an exercise and hypocaloric healthy eating intervention on indices of psychological health status, hypothalamic-pituitary-adrenal axis regulation and immune function after early-stage breast cancer: a randomised controlled trial. Breast Cancer Research, 16(2), R39.
  • St. Jude Children’s Research Hospital (2019). Acute Lymphoblastic Leukemia (ALL). (n.d.). Retrieved from https://www.stjude.org/disease/acute-lymphoblastic-leukemia-all.html.
  • van Brussel, M., Takken, T., Lucia, A., van der Net, J., & Helders, P. J. (2005). Is physical fitness decreased in survivors of childhood leukemia? A systematic review. Leukemia, 19(1), 13.
  • Warner, J. T., Bell, W., Webb, D. K., & Gregory, J. W. (1998). Daily energy expenditure and physical activity in survivors of childhood malignancy. Pediatric Research, 43(5), 607.

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