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Physical fitness throughout chemotherapy in children with acute lymphoblastic leukaemia and lymphoma

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Abstract

Acute lymphoblastic leukaemia/lymphoma (ALL/LBL) and its treatment interfere with normal physical functioning. However, it remains unclear how physical fitness (PF) is affected throughout treatment for ALL/LBL. Sixty-two patients (2.1 to 18.3 years) treated for ALL/LBL underwent four physical tests at nine timepoints from baseline up to 6 months post-treatment. We assessed muscle strength of the quadriceps and tibialis anterior, standing broad jump test (SBJ) for functional mobility and six-minute walk test (6MWT) for endurance. One-sample t-tests were used to compare our results to the norm at each timepoint. Norm-referenced Z-scores were predicted based on time, risk group and age at diagnosis, using linear mixed models. Quadriceps strength, SBJ and 6MWT scores were significantly lower than norm values at all timepoints from diagnosis up to 6 months after maintenance therapy. Significant decreases over time were encountered for quadriceps strength and SBJ, mainly occurring after induction therapy (F = 3.568, p < 0.001 and F = 2.699, p = 0.008, respectively). Age at diagnosis was a significant predictor for tibialis anterior strength (F = 5.266, p = 0.025), SBJ (F = 70.422, p < 0.001) and 6MWT (F = 15.890, p < 0.001) performances, with lower results in adolescents at all timepoints. Six months after treatment, quadriceps strength, 6MWT and SBJ scores remained below expected levels.

Conclusion: The decreased quadriceps strength, functional mobility and endurance at all timepoints, with a large deterioration following induction therapy, suggest the need for early interventions, specifically in the adolescent population. The continued low results 6 months after therapy emphasise the importance of long-term rehabilitation.

What is Known:

•Acute lymphoblastic leukaemia is the most common type of cancer among children, with increasing survival rates due to therapeutic improvements.

•Acute lymphoblastic leukaemia/lymphoma and its treatment can cause muscle weakness, neuromuscular toxicity and a decreased cardiopulmonary fitness. Together with physical inactivity, this can result in a decreased physical fitness.

What is New:

•Quadriceps strength, functional mobility and endurance are decreased during treatment for acute lymphoblastic leukaemia/lymphoma. The lowest measurements are observed after induction therapy, suggesting the need for early interventions.

•We observed continued lower results for quadriceps strength, functional mobility and endurance at the end of treatment, up to 6 months after therapy, supporting the need for long-term rehabilitation.

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Abbreviations

6MWT:

Six-minute walk test

6MP:

6-Mercaptopurine

AIC:

Akaike’s Information Criteria

ALL:

Acute lymphoblastic leukaemia

AR:

Average risk

ARA-C:

Cytarabine

CR:

Complete remission

D:

Day

Df:

Degrees of freedom

EORTC-CLG:

European Organisation for Research and Treatment of Cancer, Children’s Leukaemia Group

H:

Hour

IT:

Intrathecally

IV:

Intravenously

LBL:

Lymphoblastic lymphoma

MTX:

Methotrexate

N:

Number of observations

PF:

Physical fitness

PO:

Orally

POEM:

Paediatric Oncology Exercise Manual

SBJ:

Standing broad jump

SD:

Standard deviation

Sig:

Significance

T:

Timepoint

VHR:

Very high risk

VLR:

Very low risk

References

  1. Hunger SP, Mullighan CG (2015) Acute lymphoblastic leukemia in children. N Engl J Med 373:1541–1552. https://doi.org/10.1056/nejmra1400972

    Article  CAS  Google Scholar 

  2. Intermesoli T, Weber A, Leoncin M et al (2022) Lymphoblastic lymphoma: a concise review. Curr Oncol Rep 24:1–12. https://doi.org/10.1007/s11912-021-01168-x

    Article  CAS  Google Scholar 

  3. Cooper SL, Brown PA (2015) Treatment of pediatric acute lymphoblastic leukemia. Pediatr Clin North Am 62:61–73

    Article  Google Scholar 

  4. Domenech C, Suciu S, De Moerloose B et al (2014) Dexamethasone (6 mg/m2/day) and prednisolone (60 mg/m2/day) were equally effective as induction therapy for childhood acute lymphoblastic leukemia in the EORTC CLG 58951 randomized trial. Haematologica 99:1220–1227. https://doi.org/10.3324/haematol.2014.103507

    Article  CAS  Google Scholar 

  5. Simioni C, Zauli G, Martelli AM et al (2018) Physical training interventions for children and teenagers affected by acute lymphoblastic leukemia and related treatment impairments. Oncotarget 9:17199–17209

    Article  Google Scholar 

  6. Hartman A, van den Bos C, Stijnen T, Pieters R (2008) Decrease in peripheral muscle strength and ankle dorsiflexion as long-term side effects of treatment for childhood cancer. Pediatr Blood Cancer 50:833–837. https://doi.org/10.1002/pbc.21325

    Article  Google Scholar 

  7. Suzuki D, Kobayashi R, Sano H et al (2018) Sarcopenia after induction therapy in childhood acute lymphoblastic leukemia: its clinical significance. Int J Hematol 107:486–489. https://doi.org/10.1007/s12185-017-2388-9

    Article  Google Scholar 

  8. San Juan AF, Chamorro-Viña C, Maté-Muñoz JL et al (2008) Functional capacity of children with leukemia. Int J Sports Med 29:163–167. https://doi.org/10.1055/s-2007-964908

    Article  CAS  Google Scholar 

  9. van Brussel M, Takken T, Lucia A et al (2005) Is physical fitness decreased in survivors of childhood leukemia? A systematic review. Leukemia 19:13–17

    Article  Google Scholar 

  10. Ness KK, Kaste SC, Zhu L et al (2015) Skeletal, neuromuscular and fitness impairments among children with newly diagnosed acute lymphoblastic leukemia. Leuk Lymphoma 56:1004–1011. https://doi.org/10.3109/10428194.2014.944519

    Article  CAS  Google Scholar 

  11. Rayar M, Webber CE, Nayiager T et al (2013) Sarcopenia in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol 35:98–102. https://doi.org/10.1097/MPH.0b013e318279eea2

    Article  Google Scholar 

  12. Söntgerath R, Eckert K (2015) Impairments of lower extremity muscle strength and balance in childhood cancer patients and survivors: a systematic review. Pediatr Hematol Oncol 32:585–612. https://doi.org/10.3109/08880018.2015.1079756

    Article  CAS  Google Scholar 

  13. Manchola-González JD, Bagur-Calafat C, Girabent-Farrés M et al (2020) Effects of a home-exercise programme in childhood survivors of acute lymphoblastic leukaemia on physical fitness and physical functioning: results of a randomised clinical trial. Support Care Cancer 28:3171–3178. https://doi.org/10.1007/s00520-019-05131-2

    Article  Google Scholar 

  14. Mody R, Li S, Dover DC et al (2008) Twenty-five-year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Blood 111:5515–5523. https://doi.org/10.1182/blood-2007-10-117150

    Article  CAS  Google Scholar 

  15. Antwi GO, Jayawardene W, Lohrmann DK, Mueller EL (2019) Physical activity and fitness among pediatric cancer survivors: a meta-analysis of observational studies. Support Care Cancer 27

  16. Morales JS, Valenzuela PL, Rincón-Castanedo C et al (2018) Exercise training in childhood cancer: a systematic review and meta-analysis of randomized controlled trials. Cancer Treat Rev 70:154–167

    Article  Google Scholar 

  17. Lemay V, Caru M, Samoilenko M et al (2020) Physical activity and sedentary behaviors in childhood acute lymphoblastic leukemia survivors. J Pediatr Hematol Oncol 42:53–60. https://doi.org/10.1097/MPH.0000000000001594

    Article  Google Scholar 

  18. Marchese VG, Chiarello LA, Lange BJ (2003) Strength and functional mobility in children with acute lymphoblastic leukemia. Med Pediatr Oncol 40:230–232. https://doi.org/10.1002/mpo.10266

    Article  Google Scholar 

  19. Muratt MD, Perondi MB, Greve JMDA et al (2011) Strength capacity in young patients who are receiving maintenance therapy for acute lymphoblastic leukemia: a case-control study. Clinics 66:1277–1281

    Article  Google Scholar 

  20. Bianco A, Patti A, Thomas E et al (2014) Evaluation of fitness levels of children with a diagnosis of acute leukemia and lymphoma after completion of chemotherapy and autologous hematopoietic stem cell transplantation. Cancer Med 3:385–389. https://doi.org/10.1002/cam4.193

    Article  Google Scholar 

  21. Mizrahi D, Fardell JE, Cohn RJ et al (2020) The 6-minute walk test is a good predictor of cardiorespiratory fitness in childhood cancer survivors when access to comprehensive testing is limited. Int J Cancer 147:847–855. https://doi.org/10.1002/ijc.32819

    Article  CAS  Google Scholar 

  22. Hung SH, Rankin A, Virji-Babul N et al (2017) Associating physical activity levels with motor performance and physical function in childhood survivors of acute lymphoblastic leukemia. Physiother Canada 69:57–64. https://doi.org/10.3138/ptc.2015-67LHC

    Article  Google Scholar 

  23. Hartman A, Hop W, Takken T et al (2013) Motor performance and functional exercise capacity in survivors of pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer. https://doi.org/10.1002/pbc.24243

    Article  Google Scholar 

  24. Mondelaers V, Suciu S, De Moerloose B et al (2017) Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951. Haematologica 102:1727–1738. https://doi.org/10.3324/haematol.2017.165845

    Article  CAS  Google Scholar 

  25. De Moerloose B, Suciu S, Bertrand Y et al (2010) Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951. Blood 116:36–44. https://doi.org/10.1182/blood-2009-10-247965

    Article  CAS  Google Scholar 

  26. Hébert LJ, Maltais DB, Lepage C et al (2011) Isometric muscle strength in youth assessed by hand-held dynamometry. Pediatr Phys Ther 23:289–299. https://doi.org/10.1097/PEP.0b013e318227ccff

    Article  Google Scholar 

  27. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories (2002) ATS Statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 166:111–117. https://doi.org/10.1164/ajrccm.166.1.at1102

    Article  Google Scholar 

  28. Bianco A, Jemni M, Thomas E et al (2015) A systematic review to determine reliability and usefulness of the field-based test batteries for the assessment of physical fitness in adolescents – The ASSO Project. Int J Occup Med Environ Health 28(3):445

    Article  Google Scholar 

  29. Beenakker EA, van der Hoeven J, Fock J, Maurits N (2001) Reference values of maximum isometric muscle force obtained in 270 children aged 4–16 years by hand-held dynamometry. Neuromuscul Disord 11:441–446. https://doi.org/10.1016/S0960-8966(01)00193-6

    Article  CAS  Google Scholar 

  30. Tomkinson GR, Carver KD, Atkinson F et al (2018) European normative values for physical fitness in children and adolescents aged 9–17 years: results from 2 779 165 Eurofit performances representing 30 countries. Br J Sports Med 52:1445–1456. https://doi.org/10.1136/bjsports-2017-098253

    Article  Google Scholar 

  31. De Miguel-Etayo P, Gracia-Marco L, Ortega FB et al (2014) Physical fitness reference standards in European children: the IDEFICS study. Int J Obes 38:S57–S66. https://doi.org/10.1038/ijo.2014.136

    Article  Google Scholar 

  32. Latorre-Román PÁ, García-Pinillos F, Mora-López D (2017) Reference values of standing long jump in preschool children: a population-based study. Pediatr Exerc Sci 29:116–120. https://doi.org/10.1123/pes.2016-0076

    Article  Google Scholar 

  33. Geiger R, Strasak A, Treml B et al (2007) Six-minute walk test in children and adolescents. J Pediatr 150:395-399.e2. https://doi.org/10.1016/j.jpeds.2006.12.052

    Article  Google Scholar 

  34. Hayati Rezvan P, Lee KJ, Simpson JA (2015) The rise of multiple imputation: a review of the reporting and implementation of the method in medical research. BMC Med Res Methodol 15:30. https://doi.org/10.1186/s12874-015-0022-1

    Article  Google Scholar 

  35. Reinders-Messelink H, Schoemaker M, Snijders T et al (1999) Motor performance of children during treatment for acute lymphoblastic leukemia. Med Pediatr Oncol 33:545–550. https://doi.org/10.1002/(SICI)1096-911X(199912)33:6%3c545::AID-MPO4%3e3.0.CO;2-Y

    Article  CAS  Google Scholar 

  36. Teuffel O, Kuster SP, Hunger SP et al (2011) Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis. Leukemia 25:1232–1238. https://doi.org/10.1038/leu.2011.84

    Article  CAS  Google Scholar 

  37. McNeer JL, Nachman JB (2010) The optimal use of steroids in paediatric acute lymphoblastic leukaemia: no easy answers. Br J Haematol 149:638–652. https://doi.org/10.1111/j.1365-2141.2010.08192.x

    Article  CAS  Google Scholar 

  38. Inaba H, Pui C-H (2010) Glucocorticoid use in acute lymphoblastic leukaemia. Lancet Oncol 11:1096–1106. https://doi.org/10.1016/S1470-2045(10)70114-5

    Article  CAS  Google Scholar 

  39. Tan SY, Poh BK, Chong HX et al (2013) Physical activity of pediatric patients with acute leukemia undergoing induction or consolidation chemotherapy. Leuk Res 37:14–20. https://doi.org/10.1016/j.leukres.2012.09.005

    Article  Google Scholar 

  40. Coombs A, Schilperoort H, Sargent B (2020) The effect of exercise and motor interventions on physical activity and motor outcomes during and after medical intervention for children and adolescents with acute lymphoblastic leukemia: a systematic review. Crit Rev Oncol Hematol 152:103004. https://doi.org/10.1016/j.critrevonc.2020.103004

    Article  Google Scholar 

  41. Roussenq SC, Hintz LG, Rafael AD et al (2022) Level of physical activity and sedentary behavior in children and adolescents diagnosed with cancer: a systematic review. Int J Health Sci (Qassim) 16:54–63

    Google Scholar 

  42. Yildiz Kabak V, Ipek F, Unal S et al (2021) An evaluation of participation restrictions and associated factors via the ICF-CY framework in children with acute lymphoblastic leukemia receiving maintenance chemotherapy. Eur J Pediatr 180:1081–1088. https://doi.org/10.1007/s00431-020-03833-y

    Article  Google Scholar 

  43. Brito-Suárez JM, Camacho-Juárez F, Sánchez-Medina CM et al (2022) Gross motor disorders in pediatric patients with acute lymphoblastic leukemia and survivors: a systematic review. Pediatr Hematol Oncol. https://doi.org/10.1080/08880018.2022.2045409

    Article  Google Scholar 

  44. Mora E, Smith EML, Donohoe C, Hertz DL (2016) Vincristine-induced peripheral neuropathy in pediatric cancer patients. Am J Cancer Res 6:2416–2430

    CAS  Google Scholar 

  45. Chamorro-Viña C, Keats M, Culos-Reed SN (2014) Pediatric oncology exercise manual, 1st edition. The University of Calgary

  46. Braam KI, van der Torre P, Takken T et al (2016) Physical exercise training interventions for children and young adults during and after treatment for childhood cancer. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD008796.pub3

    Article  Google Scholar 

  47. Zucchetti G, Rossi F, Chamorro Vina C et al (2018) Exercise program for children and adolescents with leukemia and lymphoma during treatment: a comprehensive review. Pediatr Blood Cancer 65:1–6

    Article  Google Scholar 

  48. Lix LM, Sajobi T (2010) Testing multiple outcomes in repeated measures designs. Psychol Methods 15:268–280. https://doi.org/10.1037/a0017737

    Article  Google Scholar 

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Acknowledgements

The authors acknowledge Julie Uytterhoeven and Marine Van Hollebeke for their help in collecting data and for taking the first steps in this project.

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Authors and Affiliations

  1. Department of Oncology, Paediatric Oncology, KU Leuven, Herestraat 49, 3000, Leuven, Belgium

    Annelies Vriens, Deveny Vanrusselt, Charlotte Sleurs & Anne Uyttebroeck

  2. Department of Paediatric Haematology and Oncology, University Hospitals Leuven, Leuven, Belgium

    Annelies Vriens, Deveny Vanrusselt, Marjoke Gielis, Veerle Dirix, Ellen Vanderhenst & Anne Uyttebroeck

  3. Department of Rehabilitation Sciences, Research Group for Musculoskeletal Rehabilitation, KU Leuven, Leuven, Belgium

    Sabine Verschueren

  4. Department of Rehabilitation Sciences, Research Group for Rehabilitation in Internal Disorders, KU Leuven, Leuven, Belgium

    Thierry Troosters

  5. Department of Cognitive Neuropsychology, Tilburg University, Tilburg, The Netherlands

    Charlotte Sleurs

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  1. Annelies Vriens
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by MG, VD and EV. Data analysis was performed by CS and AV. The first draft of the manuscript was written by AV and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Anne Uyttebroeck.

Ethics declarations

Ethics approval

The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the University Hospitals of KU Leuven (Date: February 22, 2013, No: B322201317067).

Consent to participate

Written informed consent was obtained from the parents. No additional consent was requested for data sharing, so data are only available in case of additional requests and approval by the ethical committee.

Conflict of interest

The authors declare no competing interests.

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Communicated by Gregorio Milani

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Vriens, A., Verschueren, S., Vanrusselt, D. et al. Physical fitness throughout chemotherapy in children with acute lymphoblastic leukaemia and lymphoma. Eur J Pediatr 182, 813–824 (2023). https://doi.org/10.1007/s00431-022-04741-z

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