Skip to main content

Advertisement

SpringerLink
Log in

Trends in physical functioning in acute lymphoblastic leukemia and non-Hodgkin lymphoma survivors across three decades

  • Published:
Journal of Cancer Survivorship Aims and scope Submit manuscript

Abstract

Purpose

The impact of changes in therapy for childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) on the prevalence of physical performance limitations and participation restrictions among survivors is unknown. We aimed to describe the prevalence of reduced function among ALL and NHL survivors by treatment era.

Methods

Participants included survivors of childhood ALL and NHL, and a cohort of their siblings, participating in the Childhood Cancer Survivor Study (CCSS). Physical function was measured using questionnaire. The prevalence of reduced function was compared to siblings using generalized estimating equations, overall and stratified by treatment decade. Associations between organ system–specific chronic conditions (CTCAE v4.03) and function were also evaluated.

Results

Among 6511 survivors (mean age 25.9 years (standard deviation 6.5)) and 4127 siblings, risk of performance limitations (15.2% vs. 12.5%, prevalence ratio [PR] = 1.5, 95%CI = 1.3–1.6), restrictions in personal care (2.0% vs. 0.6%, PR = 3.1, 95% CI = 2.0–4.8), routine activities (5.5% vs. 1.6%, PR = 3.6, 95% CI = 2.7–4.8), and work/school attendance (8.8% vs. 2.1%, PR = 4.5, 95% CI = 3.6–5.7) was increased in survivors vs. siblings. The prevalence of survivors reporting reduced function did not decrease between the 1970s and 1990s. The presence of neurological and cardiovascular conditions was associated with reduced function regardless of treatment decade.

Conclusions

Despite changes in therapy, the prevalence of poor physical function remained constant between the 1970s and 1990s. The CCSS clinical trial registration number is NCT01120353 (registered May 6, 2010).

Implications for Cancer Survivors

Our findings support screening for reduced physical function so that early interventions to improve physical performance and mitigate chronic disease can be initiated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Study data will be made publicly available when the study is complete at www.zenodo.com [11] and https://www.stjude.cloud/ [12].

References

  1. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, et al (eds). SEER cancer statistics review, 1975–2014, National Cancer Institute. Bethesda, MD, based on November 2016 SEER data submission, posted to the SEER web site, April 2017.

  2. Gibson TM, Mostoufi-Moab S, Stratton KL, Leisenring WM, Barnea D, Chow EJ, et al. Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970–99: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol. 2018;19:1590–601.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ness KK, Hudson MM, Jones KE, Leisenring W, Yasui Y, Chen Y, et al. Effect of temporal changes in therapeutic exposure on self-reported health status in childhood cancer survivors. Ann Intern Med. 2017;166:89–98.

    Article  PubMed  Google Scholar 

  4. Ness KK, Gurney JG, Zeltzer LK, Leisenring W, Mulrooney DA, Nathan PC, et al. The impact of limitations in physical, executive, and emotional function on health-related quality of life among adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Arch Phys Med Rehabil. 2008;89:128–36.

    Article  PubMed  Google Scholar 

  5. Salvatore AL, Ahn S, Jiang L, Lorig K, Ory MG. National study of chronic disease self-management: 6-month and 12-month findings among cancer survivors and non-cancer survivors. Psychooncology. 2015;24:1714–22.

    Article  PubMed  Google Scholar 

  6. Dixon SB, Chen Y, Yasui Y, Pui CH, Hunger SP, Silverman LB, et al. Impact of risk-stratified therapy on health status in survivors of childhood acute lymphoblastic leukemia: a report from the childhood cancer survivor study. Cancer Epidemiol Biomarkers Prev. 2021;31:150–60.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, et al. Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children’s Cancer Group. Blood. 2003;101:3809–17.

    Article  CAS  PubMed  Google Scholar 

  8. Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO, et al. Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: results of the UK Medical Research Council ALL97 randomized trial. Br J Haematol. 2005;129:734–45.

    Article  CAS  PubMed  Google Scholar 

  9. Hudson MM, Neglia JP, Woods WG, Sandlund JT, Pui CH, Kun LE, et al. Lessons from the past: opportunities to improve childhood cancer survivor care through outcomes investigations of historical therapeutic approaches for pediatric hematological malignancies. Pediatr Blood Cancer. 2012;58:334–43.

    Article  PubMed  Google Scholar 

  10. Wingard JR, Piantadosi S, Santos GW, Saral R, Vriesendorp HM, Yeager AM, et al. Allogeneic bone marrow transplantation for patients with high-risk acute lymphoblastic leukemia. J Clin Oncol. 1990;8:820–30.

    Article  CAS  PubMed  Google Scholar 

  11. CERN European Organization for Nuclear Research. Zenodo. Geneve, Switzerland. 2023. https://zenodo.org/. Accessed May 2022.

  12. St. Jude Children's Research Hospital. St. Jude Cloud. Memphis, Tennessee, United States. 2023. https://www.stjude.cloud/. Accessed May 2022

  13. Leisenring WM, Mertens AC, Armstrong GT, Stovall MA, Neglia JP, Lanctot JQ, et al. Pediatric cancer survivorship research: experience of the Childhood Cancer Survivor Study. J Clin Oncol. 2009;27:2319–27.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Robison LL, Armstrong GT, Boice JD, Chow EJ, Davies SM, Donaldson SS, et al. The Childhood Cancer Survivor Study: a National Cancer Institute-supported resource for outcome and intervention research. J Clin Oncol. 2009;27:2308–18.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Robison LL, Mertens AC, Boice JD, Breslow NE, Donaldson SS, Green DM, et al. Study design and cohort characteristics of the Childhood Cancer Survivor Study: a multi-institutional collaborative project. Med Pediatr Oncol. 2002;38:229–39.

    Article  PubMed  Google Scholar 

  16. Howell RM, Smith SA, Weathers RE, Kry SF, Stovall M. Adaptations to a generalized radiation dose reconstruction methodology for use in epidemiologic studies: an update from the MD Anderson late effect group. Radiat Res. 2019;192:169–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ness KK, Mertens AC, Hudson MM, Wall MM, Leisenring WM, Oeffinger KC, et al. Limitations on physical performance and daily activities among long-term survivors of childhood cancer. Ann Intern Med. 2005;143:639–47.

    Article  PubMed  Google Scholar 

  18. Feijen EA, Leisenring WM, Stratton KL, Ness KK, van der Pal HJ, Caron HN, et al. Equivalence ratio for daunorubicin to doxorubicin in relation to late heart failure in survivors of childhood cancer. J Clin Oncol. 2015;33:3774–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Feijen EAM, Leisenring WM, Stratton KL, Ness KK, van der Pal HJH, van Dalen EC, et al. Derivation of anthracycline and anthraquinone equivalence ratios to doxorubicin for late-onset cardiotoxicity. JAMA Oncol. 2019;5:864–71.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Green DM, Nolan VG, Goodman PJ, Whitton JA, Srivastava D, Leisenring WM, et al. The cyclophosphamide equivalent dose as an approach for quantifying alkylating agent exposure: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer. 2014;61:53–67.

    Article  CAS  PubMed  Google Scholar 

  21. CCSS The Childhood Cancer Survivor Study. Questionnaires. St. Jude Children's Research Hospital, Memphis, TN. 2023. https://ccss.stjude.org/tools-documents/questionnaires. Accessed 01 Jan 2022.

  22. Armstrong GT, Kawashima T, Leisenring W, Stratton K, Stovall M, Hudson MM, et al. Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study. J Clin Oncol. 2014;32:1218–27.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Mulrooney DA, Hyun G, Ness KK, Bhakta N, Pui CH, Ehrhardt MJ, et al. The changing burden of long-term health outcomes in survivors of childhood Acute Lymphoblastic leukaemia: a retrospective analysis of the St. Jude Lifetime Cohort Study. Lancet Haematol. 2019;6:e306–16.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Eshelman-Kent D, Kinahan KE, Hobbie W, Landier W, Teal S, Friedman D, et al. Cancer survivorship practices, services, and delivery: a report from the Children’s Oncology Group (COG) nursing discipline, adolescent/young adult, and late effects committees. J Cancer Surviv. 2011;5:345–57.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Landier W, Bhatia S, Eshelman DA, Forte KJ, Sweeney T, Hester AL, et al. Development of risk-based guidelines for pediatric cancer survivors: the Children’s Oncology Group Long-Term Follow-Up Guidelines from the Children’s Oncology Group Late Effects Committee and Nursing Discipline. J Clin Oncol. 2004;22:4979–90.

    Article  PubMed  Google Scholar 

  26. Rueegg CS, Michel G, Wengenroth L, von der Weid NX, Bergstraesser E, Kuehni CE, et al. Physical performance limitations in adolescent and adult survivors of childhood cancer and their siblings. PLoS ONE. 2012;7:e47944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Minard-Colin V, Auperin A, Pillon M, Burke GAA, Barkauskas DA, Wheatley K, et al. Rituximab for high-risk, mature B-cell non-Hodgkin’s lymphoma in children. N Engl J Med. 2020;382:2207–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dixon SB, Chen Y, Yasui Y, Pui CH, Hunger SP, Silverman LB, et al. Reduced morbidity and mortality in survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2020;38:3418–29.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Albertsen BK, Grell K, Abrahamsson J, Lund B, Vettenranta K, Jonsson OG, et al. Intermittent versus continuous PEG-Asparaginase to reduce asparaginase-associated toxicities: a NOPHO ALL2008 Randomized Study. J Clin Oncol. 2019;37:1638–46.

    Article  CAS  PubMed  Google Scholar 

  30. Mattano LA Jr, Devidas M, Nachman JB, Sather HN, Hunger SP, Steinherz PG, et al. Effect of alternate-week versus continuous dexamethasone scheduling on the risk of osteonecrosis in paediatric patients with acute lymphoblastic leukaemia: results from the CCG-1961 randomised cohort trial. Lancet Oncol. 2012;13:906–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Frisell T. Invited commentary: sibling-comparison designs, are they worth the effort? Am J Epidemiol. 2021;190:738–41.

    Article  PubMed  Google Scholar 

  32. San Juan AF, Fleck SJ, Chamorro-Vina C, Mate-Munoz JL, Moral S, Perez M, et al. Effects of an intrahospital exercise program intervention for children with leukemia. Med Sci Sports Exerc. 2007;39:13–21.

    Article  PubMed  Google Scholar 

  33. Tanir MK, Kuguoglu S. Impact of exercise on lower activity levels in children with acute lymphoblastic leukemia: a randomized controlled trial from Turkey. Rehabil Nurs. 2013;38:48–59.

    Article  PubMed  Google Scholar 

  34. Manchola-Gonzalez JD, Bagur-Calafat C, Girabent-Farres M, Serra-Grima JR, Perez RA, Garnacho-Castano MV, et al. 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. 2020;28:3171–8.

    Article  PubMed  Google Scholar 

  35. Gohar SF, Comito M, Price J, Marchese V. Feasibility and parent satisfaction of a physical therapy intervention program for children with acute lymphoblastic leukemia in the first 6 months of medical treatment. Pediatr Blood Cancer. 2011;56:799–804.

    Article  PubMed  Google Scholar 

  36. Smith WA, Ness KK, Joshi V, Hudson MM, Robison LL, Green DM. Exercise training in childhood cancer survivors with subclinical cardiomyopathy who were treated with anthracyclines. Pediatr Blood Cancer. 2013;61:942–5.

    Article  Google Scholar 

  37. Schranz C, Kruse A, Belohlavek T, Steinwender G, Tilp M, Pieber T, et al. Does home-based progressive resistance or high-intensity circuit training improve strength, function, activity or participation in children with cerebral palsy? Arch Phys Med Rehabil. 2018;99:2457-64 e4.

    Article  PubMed  Google Scholar 

  38. Oldridge N, Pakosh M, Grace SL. A systematic review of recent cardiac rehabilitation meta-analyses in patients with coronary heart disease or heart failure. Future Cardiol. 2019;15:227–49.

    Article  CAS  PubMed  Google Scholar 

  39. Imran HM, Baig M, Erqou S, Taveira TH, Shah NR, Morrison A, et al. Home-based cardiac rehabilitation alone and hybrid with center-based cardiac rehabilitation in heart failure: a systematic review and meta-analysis. J Am Heart Assoc. 2019;8:e012779.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Courneya KS, Mackey JR, Bell GJ, Jones LW, Field CJ, Fairey AS. Randomized controlled trial of exercise training in postmenopausal breast cancer survivors: cardiopulmonary and quality of life outcomes. J Clin Oncol. 2003;21:1660–8.

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Cancer Institute (U01CA055727, G. T. Armstrong, Principal Investigator). Support to St. Jude Children’s Research Hospital was also provided by the Cancer Center Support (CORE) grant (P30CA021765, C. Roberts, Principal Investigator) and the American Lebanese Syrian Associated Charities (ALSAC).

Author information

Authors and Affiliations

  1. Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Carmen L. Wilson, Robyn E. Partin, Geehong Hyun, Gregory T. Armstrong, Yutaka Yasui, Stephanie B. Dixon, Matthew J. Ehrhardt, Leslie L. Robison & Kirsten K. Ness

  2. Department of Hematology/Oncology, Riley Children’s Hospital, Indianopolis, IN, USA

    Kari L. Bjornard

  3. Cancer Prevention and Control Program, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA

    Nina S. Kadan-Lottick

  4. Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    Paul C. Nathan

  5. Department of Medicine, Duke University, Durham, NC, USA

    Kevin C. Oeffinger

  6. Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA

    Robert J. Hayashi

  7. Cancer Prevention and Clinical Statistics Program, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Wendy M. Leisenring

  8. Radiation Physics Department, The University of Texas at MD Anderson Cancer Center, Houston, TX, USA

    Rebecca M. Howell

  9. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Stephanie B. Dixon & Matthew J. Ehrhardt

Authors
  1. Carmen L. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kari L. Bjornard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robyn E. Partin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nina S. Kadan-Lottick
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul C. Nathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kevin C. Oeffinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robert J. Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Geehong Hyun
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gregory T. Armstrong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wendy M. Leisenring
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Rebecca M. Howell
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yutaka Yasui
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Stephanie B. Dixon
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Matthew J. Ehrhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Leslie L. Robison
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Kirsten K. Ness
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Carmen L. Wilson, Kari L. Bjornard and Robyn E. Partin interpreted and analyzed data and jointly wrote the manuscript. Nina S. Kadan-Lottick, Paul C. Nathan, Kevin C. Oeffinger and Leslie L. Robison participated in study design and revised the manuscript. Geehong Hyun performed statistical analyzes, interpreted data and revised the manuscript. Robert J. Hayashi, Gregory T. Armstrong, Wendy M. Leisenring, Yutaka Yasui and Stephanie Dixon participated in study design and revised the manuscript. Matthew J. Ehrhardt participated in study design, interpreted and analyzed data and revised the manuscript. Kirsten K. Ness designed the study, supervised data collection, interpreted and analyzed data and jointly wrote the manuscript. The corresponding author had full access to the data in the study and final responsibility for the decision to submit for publication.

Corresponding author

Correspondence to Carmen L. Wilson.

Ethics declarations

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Review Board of St. Jude Children’s Research Hospital. Informed consent was obtained from all individual participants included in the study.

Consent to publish

Not applicable.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Conflict of interest

The authors have no competing interests to disclose.

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wilson, C.L., Bjornard, K.L., Partin, R.E. et al. Trends in physical functioning in acute lymphoblastic leukemia and non-Hodgkin lymphoma survivors across three decades. J Cancer Surviv (2023). https://doi.org/10.1007/s11764-023-01483-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11764-023-01483-1

Keywords

Search

Navigation