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Transplant Toxicities

Clinical and biological markers of premature aging after autologous SCT in childhood cancer

Bone Marrow Transplantation volume 52, pages 600–605 (2017)Cite this article

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Abstract

The aim of this study was to analyze the prevalence of frailty and physical health limitations among long-term survivors of high-risk neuroblastoma (HR NBL) and to investigate whether frail health is associated with variables of cardiovascular function, markers of inflammation and telomere length. A national study cohort of 19 (median age 22, range 16–30 years) long-term (>10 years) HR NBL survivors was studied and the findings were compared with 20 age- and sex-matched controls. Frailty was defined as ⩾3 of the following conditions: low muscle mass, low energy expenditure, slow running and weakness. The prevalence of frailty was significantly higher among the HR NBL survivors 9/19 (47%) than among the controls (0%). Thirteen (68%) of the survivors reported significant physical health limitations in vigorous activities, as opposed to none of the controls. The HR NBL survivors had significantly shorter telomere length and higher serum levels of high sensitivity C-reactive protein than did the controls. Frail health and poor physical functioning are prevalent among HR NBL survivors and suggest premature aging. Survivors with gonadal damage, very low fat mass percentage, low glycosylated hemoglobin A1c and increased common carotid artery intima-media thickness may be more prone to early aging after high dose therapy.

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References

  1. Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 2006; 355: 1572–1582.

    Article  CAS  Google Scholar 

  2. Mertens AC, Yasui Y, Liu Y, Stovall M, Hutchinson R, Ginsberg J et al. Pulmonary complications in survivors of childhood and adolescent cancer. A report from the childhood cancer survivor study. Cancer 2002; 95: 2431–2441.

    Article  Google Scholar 

  3. Johannsdottir IM, Hjermstad MJ, Moum T, Wesenberg F, Hjorth L, Schroder H et al. Increased prevalence of chronic fatigue among survivors of childhood cancers: a population-based study. Pediatr Blood Cancer 2012; 58: 415–420.

    Article  Google Scholar 

  4. Jarvela LS, Niinikoski H, Lahteenmaki PM, Heinonen OJ, Kapanen J, Arola M et al. Physical activity and fitness in adolescent and young adult long-term survivors of childhood acute lymphoblastic leukaemia. J Cancer Surviv 2010; 4: 339–345.

    Article  Google Scholar 

  5. Ness KK, Krull KR, Jones KE, Mulrooney DA, Armstrong GT, Green DM et al. Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: a report from the St Jude Lifetime cohort study. J Clin Oncol 2013; 31: 4496–4503.

    Article  Google Scholar 

  6. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001; 56: M146–M156.

    Article  CAS  Google Scholar 

  7. Ness KK, Armstrong GT, Kundu M, Wilson CL, Tchkonia T, Kirkland JL . Frailty in childhood cancer survivors. Cancer 2015; 121: 1540–1547.

    Article  Google Scholar 

  8. Vatanen A, Sarkola T, Ojala TH, Turanlahti M, Jahnukainen T, Saarinen-Pihkala UM et al. Radiotherapy-related arterial intima thickening and plaque formation in childhood cancer survivors detected with very-high resolution ultrasound during young adulthood. Pediatr Blood Cancer 2015; 62: 2000–2006.

    Article  CAS  Google Scholar 

  9. Vatanen A, Ojala TH, Sarkola T, Turanlahti M, Jahnukainen T, Saarinen-Pihkala UM et al. Left ventricular mass and ambulatory blood pressure are increased in long-term survivors of childhood cancer after autologous SCT. Bone Marrow Transplant 2016; 51: 853–855.

    Article  CAS  Google Scholar 

  10. Brodeur GM, Pritchard J, Berthold F, Carlsen NL, Castel V, Castelberry RP et al. Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 1993; 11: 1466–1477.

    Article  CAS  Google Scholar 

  11. Saarinen UM, Sariola H, Hovi L . Recurrent disseminated retinoblastoma treated by high-dose chemotherapy, total body irradiation, and autologous bone marrow rescue. Am J Pediatr Hematol Oncol 1991; 13: 315–319.

    Article  CAS  Google Scholar 

  12. Saarinen-Pihkala UM, Hovi L, Koivusalo A, Jahnukainen K, Karikoski R, Sariola H et al. Thiotepa and melphalan based single, tandem, and triple high dose therapy and autologous stem cell transplantation for high risk neuroblastoma. Pediatr Blood Cancer 2012; 59: 1190–1197.

    Article  Google Scholar 

  13. Saarinen UM, Wikstrom S, Makipernaa A, Lanning M, Perkkio M, Hovi L et al. In vivo purging of bone marrow in children with poor-risk neuroblastoma for marrow collection and autologous bone marrow transplantation. J Clin Oncol 1996; 14: 2791–2802.

    Article  CAS  Google Scholar 

  14. Kelly TL, Wilson KE, Heymsfield SB . Dual energy X-Ray absorptiometry body composition reference values from NHANES. PLoS ONE 2009; 4: e7038.

    Article  Google Scholar 

  15. Centers for Disease Control and Prevention/National Center for Health Statistics. National Health and Nutrition Examination Survey: Physical Activity and Physical Fitness. CDC: Atlanta, GA, USA, 2007. https://www.cdc.gov/nchs/data/nhanes/nhanes_07_08/manual_an.pdf.

  16. Hovi L, Kurimo M, Taskinen M, Vettenranta J, Vettenranta K, Saarinen-Pihkala UM . Suboptimal long-term physical performance in children and young adults after pediatric allo-SCT. Bone Marrow Transplant 2010; 45: 738–745.

    Article  CAS  Google Scholar 

  17. Lurbe E, Cifkova R, Cruickshank JK, Dillon MJ, Ferreira I, Invitti C et al. Management of high blood pressure in children and adolescents: recommendations of the European Society of Hypertension. J Hypertens 2009; 27: 1719–1742.

    Article  CAS  Google Scholar 

  18. O'Brien E, Murphy J, Tyndall A, Atkins N, Mee F, McCarthy G et al. Twenty-four-hour ambulatory blood pressure in men and women aged 17 to 80 years: the Allied Irish Bank Study. J Hypertens 1991; 9: 355–360.

    Article  CAS  Google Scholar 

  19. Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2014; 15: 1063–1093.

    Article  Google Scholar 

  20. Shay JW, Wright WE . Hallmarks of telomeres in ageing research. J Pathol 2007; 211: 114–123.

    Article  CAS  Google Scholar 

  21. Gramatges MM, Liu Q, Yasui Y, Okcu MF, Neglia JP, Strong LC et al. Telomere content and risk of second malignant neoplasm in survivors of childhood cancer: a report from the childhood cancer survivor study. Clin Cancer Res 2014; 20: 904–911.

    Article  CAS  Google Scholar 

  22. Fernandez-Alvira JM, Fuster V, Dorado B, Soberon N, Flores I, Gallardo M et al. Short telomere load, telomere length, and subclinical atherosclerosis: the PESA study. J Am Coll Cardiol 2016; 67: 2467–2476.

    Article  CAS  Google Scholar 

  23. Abdelhafiz AH, Sinclair AJ . Low HbA1c and increased mortality risk-is frailty a confounding factor? Aging Dis 2015; 6: 262–270.

    Article  Google Scholar 

  24. Jarvisalo MJ, Harmoinen A, Hakanen M, Paakkunainen U, Viikari J, Hartiala J et al. Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol 2002; 22: 1323–1328.

    Article  CAS  Google Scholar 

  25. Adriaensen W, Mathei C, van Pottelbergh G, Vaes B, Legrand D, Wallemacq P et al. Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study. Age (Dordr) 2014; 36: 457–467.

    Article  CAS  Google Scholar 

  26. Wang G, Christoffel KK, Brickman WJ, Hong X, Arguelles L, Zhang S et al. C-reactive protein in adolescent twins: patterns and relationship to adiposity. J Clin Endocrinol Metab 2011; 96: 3226–3233.

    Article  CAS  Google Scholar 

  27. Cesari M, Kritchevsky SB, Baumgartner RN, Atkinson HH, Penninx BW, Lenchik L et al. Sarcopenia, obesity, and inflammation—results from the trial of angiotensin converting enzyme inhibition and novel cardiovascular risk factors study. Am J Clin Nutr 2005; 82: 428–434.

    Article  CAS  Google Scholar 

  28. Leung KM, Alrabeeah K, Carrier S . Update on testosterone replacement therapy in hypogonadal men. Curr Urol Rep 2015; 16: 57.

    Article  Google Scholar 

  29. Huhtaniemi I, Forti G . Male late-onset hypogonadism: pathogenesis, diagnosis and treatment. Nat Rev Urol 2011; 8: 335–344.

    Article  CAS  Google Scholar 

  30. Rochira V, Diazzi C, Santi D, Brigante G, Ansaloni A, Decaroli MC et al. Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study. Andrology 2015; 3: 298–308.

    Article  CAS  Google Scholar 

  31. Sheppard VB, Faul LA, Luta G, Clapp JD, Yung RL, Wang JH et al. Frailty and adherence to adjuvant hormonal therapy in older women with breast cancer: CALGB protocol 369901. J Clin Oncol 2014; 32: 2318–2327.

    Article  Google Scholar 

  32. Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010; 363: 1324–1334.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Drs Päivi Lähteenmäki, Merja Möttönen, Pekka Riikonen and Katriina Parto for identifying the NBL long-term survivors in local hospital records.

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Authors and Affiliations

  1. Division of Hematology-Oncology and Stem Cell Transplantation, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    A Vatanen, M Kurimo, U M Saarinen-Pihkala & K Jahnukainen

  2. Department of Women’s and Children’s Health, Karolinska Institute and University Hospital, Stockholm, Sweden

    M Hou, T Huang, O Söder & K Jahnukainen

  3. Division of Pediatric Nephrology and Transplantation, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    T Jahnukainen

  4. Division of Cardiology, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    T H Ojala, T Sarkola & M Turanlahti

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  1. A Vatanen
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  2. M Hou
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  3. T Huang
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  5. T Jahnukainen
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  7. T H Ojala
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Correspondence to A Vatanen.

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Supplementary Information accompanies this paper on Bone Marrow Transplantation website

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Vatanen, A., Hou, M., Huang, T. et al. Clinical and biological markers of premature aging after autologous SCT in childhood cancer. Bone Marrow Transplant 52, 600–605 (2017). https://doi.org/10.1038/bmt.2016.334

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