Effect of a Cross-Training and Resistance Exercise Routine on IL-15 in Adults with Type B Acute Lymphoblastic Leukemia During the Induction Phase: Randomized Pilot Study

Overview

Journal J Funct Morphol Kinesiol

Date 2024 Mar 27

PMID 38535413

Authors

Adan German Gallardo Rodriguez

Irma Olarte Carrillo

Adolfo Martinez Tovar

Rafael Ceron Maldonado

Emmanuel Martinez Moreno

Christian Omar Ramos Penafiel

Affiliations

Soon will be listed here.

Abstract

IL-15 is a proinflammatory myokine essential for activating NK cells and CD8+ T lymphocytes, and its overexpression has been related to reducing overall survivorship in patients with acute lymphoblastic leukemia (ALL). Physical exercise has been shown to be safe, feasible, and beneficial in hematological cancers. Exercise requires the activation of muscles that secrete cytokines, such as IL-15, causing immune mobilization. The objective was to compare the outcomes of two training routines on IL-15 and survival prognosis in adult patients diagnosed with ALL. A blind randomized clinical study was carried out where twenty-three peripheral blood samples were obtained pre and postexercise intervention from patients categorized into three types of intervention: the resistance exercise group (REG), the cross-training exercise group (CEG), and the control group (CG). Changes in IL-15 levels during the intervention were not significant in any of the groups (CG = 0.237, REG = 0.866, and CEG = 0.678). However, 87.5% of patients who received an exercise intervention achieved remission, while only 21.73% experienced a relapse. There were no deaths during the study. Although IL-15 level adaptation in the REG and the CG performed similarly, the REG induced a better clinical outcome. Resistance exercises may help improve survival prognosis and reduce relapses in patients with ALL.

References

Simioni C, Zauli G, Martelli A, Vitale M, Ultimo S, Milani D . Physical training interventions for children and teenagers affected by acute lymphoblastic leukemia and related treatment impairments. Oncotarget. 2018; 9(24):17199-17209. PMC: 5908317. DOI: 10.18632/oncotarget.24762. View

Wadai G . Evaluation of Serum Interleukin-15 in Acute Lymphoid and Myeloid Leukemia Patients. Arch Razi Inst. 2023; 77(5):1895-1899. PMC: 10133639. DOI: 10.22092/ARI.2022.359504.2435. View

Becker-Hapak M, Shrestha N, McClain E, Dee M, Chaturvedi P, Leclerc G . A Fusion Protein Complex that Combines IL-12, IL-15, and IL-18 Signaling to Induce Memory-Like NK Cells for Cancer Immunotherapy. Cancer Immunol Res. 2021; 9(9):1071-1087. PMC: 8416787. DOI: 10.1158/2326-6066.CIR-20-1002. View

Orgel E, Tucci J, Alhushki W, Malvar J, Sposto R, Fu C . Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia. Blood. 2014; 124(26):3932-8. DOI: 10.1182/blood-2014-08-595389. View

Micielska K, Gmiat A, Zychowska M, Kozlowska M, Walentukiewicz A, Lysak-Radomska A . The beneficial effects of 15 units of high-intensity circuit training in women is modified by age, baseline insulin resistance and physical capacity. Diabetes Res Clin Pract. 2019; 152:156-165. DOI: 10.1016/j.diabres.2019.05.009. View

Yalcin A, Silay K, Balik A, Avcioglu G, Aydin A . The relationship between plasma interleukin-15 levels and sarcopenia in outpatient older people. Aging Clin Exp Res. 2017; 30(7):783-790. DOI: 10.1007/s40520-017-0848-y. View

Kurz E, Hirsch C, Dalton T, Shadaloey S, Khodadadi-Jamayran A, Miller G . Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer. Cancer Cell. 2022; 40(7):720-737.e5. PMC: 9280705. DOI: 10.1016/j.ccell.2022.05.006. View

Fiore P, Di Matteo S, Tumino N, Mariotti F, Pietra G, Ottonello S . Interleukin-15 and cancer: some solved and many unsolved questions. J Immunother Cancer. 2020; 8(2). PMC: 7674108. DOI: 10.1136/jitc-2020-001428. View

Saenz A, Stapleton S, Hernandez R, Hale G, Goldenberg N, Schwartz S . Body Mass Index at Pediatric Leukemia Diagnosis and the Risks of Relapse and Mortality: Findings from a Single Institution and Meta-analysis. J Obes. 2018; 2018:7048078. PMC: 6236800. DOI: 10.1155/2018/7048078. View

10.

Alibhai S, Durbano S, Breunis H, Brandwein J, Timilshina N, Tomlinson G . A phase II exercise randomized controlled trial for patients with acute myeloid leukemia undergoing induction chemotherapy. Leuk Res. 2015; . DOI: 10.1016/j.leukres.2015.08.012. View

11.

Park K, Park S, Kang S . Effects of resistance exercise on adipokine factors and body composition in pre- and postmenopausal women. J Exerc Rehabil. 2019; 15(5):676-682. PMC: 6834705. DOI: 10.12965/jer.1938368.184. View

12.

Williams A, Bate J, Brooks R, Chisholm J, Clarke S, Dixon E . Immune reconstitution in children following chemotherapy for acute leukemia. EJHaem. 2022; 1(1):142-151. PMC: 9176016. DOI: 10.1002/jha2.27. View

13.

Yang Y, Lundqvist A . Immunomodulatory Effects of IL-2 and IL-15; Implications for Cancer Immunotherapy. Cancers (Basel). 2020; 12(12). PMC: 7761238. DOI: 10.3390/cancers12123586. View

14.

Sindaco P, Pandey H, Isabelle C, Chakravarti N, Brammer J, Porcu P . The role of interleukin-15 in the development and treatment of hematological malignancies. Front Immunol. 2023; 14:1141208. PMC: 10157481. DOI: 10.3389/fimmu.2023.1141208. View

15.

Figueras M, Busquets S, Carbo N, Barreiro E, Almendro V, Argiles J . Interleukin-15 is able to suppress the increased DNA fragmentation associated with muscle wasting in tumour-bearing rats. FEBS Lett. 2004; 569(1-3):201-6. DOI: 10.1016/j.febslet.2004.05.066. View

16.

Quinn L, Anderson B, Strait-Bodey L, Stroud A, Argiles J . Oversecretion of interleukin-15 from skeletal muscle reduces adiposity. Am J Physiol Endocrinol Metab. 2008; 296(1):E191-202. PMC: 2636988. DOI: 10.1152/ajpendo.90506.2008. View

17.

Orgel E, Genkinger J, Aggarwal D, Sung L, Nieder M, Ladas E . Association of body mass index and survival in pediatric leukemia: a meta-analysis. Am J Clin Nutr. 2016; 103(3):808-17. PMC: 6546230. DOI: 10.3945/ajcn.115.124586. View

18.

Perez-Lopez A, Valades D, Vazquez Martinez C, de Cos Blanco A, Bujan J, Garcia-Honduvilla N . Serum IL-15 and IL-15Rα levels are decreased in lean and obese physically active humans. Scand J Med Sci Sports. 2017; 28(3):1113-1120. DOI: 10.1111/sms.12983. View

19.

Waldmann T . The biology of IL-15: implications for cancer therapy and the treatment of autoimmune disorders. J Investig Dermatol Symp Proc. 2013; 16(1):S28-30. DOI: 10.1038/jidsymp.2013.8. View

20.

Wu S, Fischer L, Gokbuget N, Schwartz S, Burmeister T, Notter M . Expression of interleukin 15 in primary adult acute lymphoblastic leukemia. Cancer. 2009; 116(2):387-92. DOI: 10.1002/cncr.24729. View