Document Type : Research Paper

Authors

1 Department of Biological Sciences in Sports, Faculty of Sport Sciences and Health, Shahid Beheshti University, Tehran, Iran

2 Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Objectives: Chemotherapy induced immune-suppression is a side effect of cancer treatment. Exercise is an effective regulator for the survival and function of immune cells. Therefore, the aim of this study was to investigate the effect of high intensity interval training (HIIT) on neutropenia in cancer patients after hematopoietic stem cell transplantation.
Materials and Methods: 20 patients with lymphoma and multiple myeloma were divided into exercise and control groups. Exercise group performed a graded exercise test and then for five days, performed exercise training on ergo cycle for 24 minutes (three periods of four min work and rest with 80 and 40 % of peak power), while the control group did not have any exercise activities. Blood sampling was done daily during the treatment period. Statistical analysis of the data was done with SPSS software and ANOVA, independent t and Mann-Whitney U tests at a significance level of less than 0.05.
Results: The number of white blood cells on the day of cell collection and leukocyte transplantation was significantly higher in the exercise group than in the control group (P<0.05). The amount and number of days of administration of granulocyte colony stimulating factor before transplantation in the exercise group were significantly lower than the control group (P<0.05). The number of days of neutropenia and the amount of antibiotics used did not show any significant difference between the two groups (P>0.05).
Conclusion: Considering the positive effect of training on leukocyte engraftment, probably patients can benefit from training in addition to routine care.

Keywords

  1. Lyman GH, Michels SL, Reynolds MW, Barron R, Tomic KS, Yu J. Risk of mortality in patients with cancer who experience febrile neutropenia. Cancer. 2010;116(23):5555-63.
  2. van Haren IEPM, Staal JB, Potting CM, Atsma F, Hoogeboom TJ, Blijlevens NMA, et al. Physical exercise prior to hematopoietic stem cell transplantation: A feasibility study. Physiother Theory Pract. 2018;34(10):747–56.
  3. Trivedi M, Martinez S, Corringham S, Medley K, Ball ED. Optimal use of G-CSF administration after hematopoietic SCT. Bone Marrow Transplant. 2009;43(12):895–908.
  4. Greenbaum AM, Link DC. Mechanisms of G-CSF-mediated hematopoietic stem and progenitor mobilization. Leukemia. Nature Publishing Group. 2011;25(2):211–7.
  5. Bendall, L. J. and Bradstock, K. F. G-CSF: from granulopoietic stimulant to bone marrow stem cell mobilizing agent. Cytokine and Growth Factor Reviews. 2014;25(4):355–67.
  6. Schleicher SM, Bach PB, Matsoukas K, Korenstein D. Medication overuse in oncology: current trends and future implications for patients and society. The Lancet Oncology. 2018;19(4):200–8.
  7. Lambertini, M., Del Mastro, L., Bellodi, A. and Pronzato, P. The five “Ws” for bone pain due to the administration of granulocyte-colony stimulating factors (G-CSFs). Critical Reviews in Oncology/Hematology.2014;89(1): 112–8.
  8. McBride A, Campbell K, Bikkina M, MacDonald K, Abraham I, Balu S. Cost-efficiency analyses for the US of biosimilar filgrastim-sndz, reference filgrastim, pegfilgrastim, and pegfilgrastim with on-body injector in the prophylaxis of chemotherapy-induced (febrile) neutropenia. Journal of Medical Economics. 2017;20(10):1083–93.
  9. Schauer T, Hojman P, Gehl J, Christensen JF. Exercise training as prophylactic strategy in the management of neutropenia during chemotherapy. Br J Pharmacol. 2022;179(12):2925–37.
  10. Pyne DB, Smith JA, Baker MS, Telford RD, Weidemann MJ. Neutrophil oxidative activity is differentially affected by exercise intensity and type. Journal of Science and Medicine in Sport. 2000;3(1):44-54.
  11. Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER. Neutrophil kinetics in health and disease. Trends in immunology. 2010;31(8):318-24.
  12. Brown W, Davison GW, McClean CM, Murphy MH. A systematic review of the acute effects of exercise on immune and inflammatory indices in untrained adults. Sports Medicine-Open. 2015;1(1):1-0.
  13. Mooren FC, Völker K, Klocke R, Nikol S, Waltenberger J, Krüger K. Exercise delays neutrophil apoptosis by a G-CSF-dependent mechanism. Journal of Applied Physiology. 2012;113(7):1082-90.
  14. Heijnen S, Hommel B, Kibele A, Colzato LS. Neuromodulation of aerobic exercise—a review. Frontiers in Psychology. 2016; 6:1890.
  15. Agha NH, Baker FL, Kunz HE, Graff R, Azadan R, Dolan C, et al. Vigorous exercise mobilizes CD34+ hematopoietic stem cells to peripheral blood via the β2-adrenergic receptor. Brain, Behavior, and Immunity. 2018; 68:66-75.
  16. Spiegel A, Shivtiel S, Kalinkovich A, Ludin A, Netzer N, Goichberg P, et al. Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling. Nature Immunology. 2007;8(10):1123-31.
  17. Großek A, Elter T, Oberste M, Wolf F, Joisten N, Hartig P, Walzik D, Rosenberger F, Kiesl D, Wahl P, Bloch W. Feasibility and suitability of a graded exercise test in patients with aggressive hemato-oncological disease. Supportive Care in Cancer. 2021;29:4859-66.
  18. Karvinen KH, Esposito D, Raedeke TD, Vick J, Walker PR. Effect of an exercise training intervention with resistance bands on blood cell counts during chemotherapy for lung cancer: a pilot randomized controlled trial. Springerplus. 2014;3(1):1-8.
  19. Büttner P, Mosig S, Lechtermann A, Funke H, Mooren FC. Exercise affects the gene expression profiles of human white blood cells. Journal of Applied Physiology. 2007;102(1):26-36.
  20. Kenyon M, Babic A. The European blood and marrow transplantation textbook for nurses: Under the auspices of EBMT. London: Springer; 2018.
  21. Schwella N, Beyer J, Schwaner I, Heuft HG, Rick O, Huhn D, et al. Impact of preleukapheresis cell counts on collection results and correlation of progenitor-cell dose with engraftment after high-dose chemotherapy in patients with germ cell cancer. J Clin Oncol. 1996;14(4):1114–21.
  22. Bonsignore MR, Morici G, Santoro A, Pagano M, Cascio L, Bonanno A, et al. Circulating hematopoietic progenitor cells in runners. Journal of Applied Physiology. 2002;93(5):1691-7.
  23. Wardyn GG, Rennard SI, Brusnahan SK, McGuire TR, Carlson ML, Smith LM, et al. Effects of exercise on hematological parameters, circulating side population cells, and cytokines. Experimental hematology. 2008;36(2):216-23.
  24. De Lisio, M. and Parise, G. Characterization of the effects of exercise training on hematopoietic stem cell quantity and function. Journal of Applied Physiology. 2012;113(10):1576–84.
  25. Stelzer I, Fuchs R, Schraml E, Quan P, Hansalik M, Pietschmann P, et al. Decline of bone marrow–derived hematopoietic progenitor cell quality during aging in the rat. Experimental Aging Research. 2010;36(3):359-70.
  26. Su SH, Jen CJ, Chen HI. NO signaling in exercise training-induced anti-apoptotic effects in human neutrophils. Biochemical and Biophysical Research Communications. 2011;405(1):58-63.
  27. Van Staveren S, Ten Haaf T, Klöpping M, Hilvering B, Tinnevelt GH, De Ruiter K, et al. Multi-dimensional flow cytometry analysis reveals increasing changes in the systemic neutrophil compartment during seven consecutive days of endurance exercise. PLoS One. 2018;13(10): e0206175.
  28. Dimeo F, Fetscher S, Lange W, Mertelsmann R, Keul J. Effects of aerobic exercise on the physical performance and incidence of treatment-related complications after high-dose chemotherapy. Blood, The Journal of the American Society of Hematology. 1997;90(9):3390-4.
  29. Van Waart H, Stuiver MM, van Harten WH, Geleijn E, Kieffer JM, Buffart LM, et al. Effect of low-intensity physical activity and moderate-to high-intensity physical exercise during adjuvant chemotherapy on physical fitness, fatigue, and chemotherapy completion rates: results of the PACES randomized clinical trial. J Clin Oncol. 2015;33(17):1918-27.
  30. Mijwel S, Bolam KA, Wengström Y, Rundqvist H. Effects of exercise during chemotherapy on hospitalization and chemotherapy completion: the OptiTrain breast cancer trial: 3173 Board# 219 May 31 3: 30 PM-5: 00 PM. Medicine & Science in Sports & Exercise. 2019;51(6S):881.
  31. Xu YJ, Cheng JC, Lee JM, Huang PM, Huang GH, Chen CC. A walk-and-eat intervention improves outcomes for patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy. The Oncologist. 2015;20(10):1216-22.
  32. Jarden M, Baadsgaard MT, Hovgaard DJ, Boesen E, Adamsen L. A randomized trial on the effect of a multimodal intervention on physical capacity, functional performance and quality of life in adult patients undergoing allogeneic SCT. Bone Marrow Transplantation. 2009;43(9):725-37.
  33. Baumann FT, Zimmer P, Finkenberg K, Hallek M, Bloch W, Elter T. Influence of endurance exercise on the risk of pneumonia and fever in leukemia and lymphoma patients undergoing high dose chemotherapy. A pilot study. Journal of Sports Science & Medicine. 2012;11(4):638.
  34. Shim YJ, Kim HJ, Oh SC, Lee SI, Choi SW. Exercise during adjuvant treatment for colorectal cancer: treatment completion, treatment-related toxicities, body composition, and serum level of adipokines. Cancer Management and Research. 2019;11:5403.
  35. Chamorro-Vina C, Ruiz JR, Santana-Sosa E, Madero L, Pérez M, Fleck SJ, et al. Exercise during hematopoietic stem cell transplant hospitalization in children. Medicine and Science in Sports and Exercise. 2010;42(6):1045-53.
  36. Courneya KS, Segal RJ, Mackey JR, Gelmon K, Reid RD, Friedenreich CM, et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol. 2007;25(28):4396-404.
  37. Furze RC, Rankin SM. Neutrophil mobilization and clearance in the bone marrow. Immunology. 2008;125(3):281-8.
  38. Panopoulos AD, Watowich SS. Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and ‘emergency’hematopoiesis. Cytokine. 2008;42(3):277-88.
  39. Souza LR, Silva E, Calloway E, Cabrera C, McLemore ML. G‐CSF activation of AKT is not sufficient to prolong neutrophil survival. Journal of Leukocyte Biology. 2013;93(6):883-93.
  40. Castellani S, D’Oria S, Diana A, Polizzi AM, Di Gioia S, Mariggiò MA, et al. G-CSF and GM-CSF modify neutrophil functions at concentrations found in cystic fibrosis. Scientific Reports. 2019;9(1):1.
  41. Maryanovich M, Zahalka AH, Pierce H, Pinho S, Nakahara F, Asada N, et al. Adrenergic nerve degeneration in bone marrow drives aging of the hematopoietic stem cell niche. Nature Medicine. 2018;24(6):782-91.
  42. Ugrayová S, Švec P, Hric I, Šardzíková S, Kubáňová L, Penesová A, et al. Gut microbiome suffers from hematopoietic stem cell transplantation in childhood and its characteristics are positively associated with intra-hospital physical exercise. Biology. 2022;11(5):785.
  43. Metsios GS, Moe RH, Kitas GD. Exercise and inflammation. Best Practice & Research Clinical Rheumatology. 2020;34(2):101504.