Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Quality of Life

Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD)

Bone Marrow Transplantation volume 45, pages 762–769 (2010)Cite this article

Abstract

This study examined factors accounting for functional performance limitations in 100 long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD). Functional performance, measured by the SF-36 physical component summary score, was substantially lower (mean=36.8±10.7) than the US population norm of 50 (P<0.001). The most severe decrements were in physical function (mean=38.8±10.9) and physical role function (mean=37.88±11.88); 68% of respondents exceeded the five-point threshold of minimum clinically important difference below the norm on these subscales. Controlling for age and gender, six variables explained 56% of the variance in functional performance: time since cGVHD diagnosis, cGVHD severity, intensity of immunosuppression, comorbidity, functional capacity (distance walked in 2 min, grip strength, and range of motion), and cGVHD symptom bother (F=11.26; P<0.001). Significant independent predictors of impaired performance were intensive systemic immunosuppression, reduced capacity for ambulation, and greater cGVHD symptom bother (P<0.05). Symptom bother had a direct effect on functional performance, as well as an indirect effect partially mediated by functional capacity (Sobel test, P=0.004). Results suggest two possible mechanisms underlying impaired functional performance in survivors with cGVHD and underscore the importance of testing interventions to enhance functional capacity and reduce symptom bother.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Baker KS, Gurney JG, Ness KK, Bhatia R, Forman SJ, Francisco L et al. Late effects in survivors of chronic myeloid leukemia treated with hematopoietic cell transplantation: results from the Bone Marrow Transplant Survivor Study. Blood 2004; 104: 1898–1906.

    Article  CAS  PubMed  Google Scholar 

  2. Bhatia S, Francisco L, Carter A, Sun CL, Baker KS, Gurney JG et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study. Blood 2007; 110: 3784–3792.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Flowers ME, Parker PM, Johnston LJ, Matos AV, Storer B, Bensinger WI et al. Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood 2002; 100: 415–419.

    Article  CAS  PubMed  Google Scholar 

  4. Valcarcel D, Martino R, Caballero D, Martin J, Ferra C, Nieto JB et al. Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. J Clin Oncol 2008; 26: 577–584.

    Article  CAS  PubMed  Google Scholar 

  5. Lee SJ, Vogelsang G, Flowers ME . Chronic graft-versus-host disease. Biol Blood Marrow Transplant 2003; 9: 215–233.

    Article  CAS  PubMed  Google Scholar 

  6. Chiodi S, Spinelli S, Ravera G, Petti AR, Van Lint MT, Lamparelli T et al. Quality of life in 244 recipients of allogeneic bone marrow transplantation. Br J Haematol 2000; 110: 614–619.

    Article  CAS  PubMed  Google Scholar 

  7. Heinonen H, Volin L, Zevon MA, Uutela A, Barrick C, Ruutu T . Stress among allogeneic bone marrow transplantation patients. Pat Educ Couns 2005; 56: 62–71.

    Article  Google Scholar 

  8. Kopp M, Holzner B, Meraner V, Sperner-Unterweger B, Kemmler G, Nguyen-Van-Tam DP et al. Quality of life in adult hematopoietic cell transplant patients at least 5 yr after treatment: a comparison with healthy controls. Eur J Haematol 2005; 74: 304–308.

    Article  PubMed  Google Scholar 

  9. Prieto JM, Saez R, Carreras E, Atala J, Sierra J, Rovira M et al. Physical and psychosocial functioning of 117 survivors of bone marrow transplantation. Bone Marrow Transplant 1996; 17: 1133–1142.

    CAS  PubMed  Google Scholar 

  10. Sutherland HJ, Fyles GM, Adams G, Hao Y, Lipton JH, Minden MD et al. Quality of life following bone marrow transplantation: a comparison of patient reports with population norms. Bone Marrow Transplant 1997; 19: 1129–1136.

    Article  CAS  PubMed  Google Scholar 

  11. Baker KS, Fraser CJ . Quality of life and recovery after graft-versus-host disease. Best Pract Res Clin Haematol 2008; 21: 333–341.

    Article  PubMed  Google Scholar 

  12. Syrjala KL, Chapko MK, Vitaliano PP, Cummings C, Sullivan KM . Recovery after allogeneic marrow transplantation: prospective study of predictors of long-term physical and psychosocial functioning. Bone Marrow Transplant 1993; 11: 319–327.

    CAS  PubMed  Google Scholar 

  13. Syrjala KL, Langer SL, Abrams JR, Storer B, Sanders JE, Flowers ME et al. Recovery and long-term function after hematopoietic cell transplantation for leukemia or lymphoma. JAMA 2004; 291: 2335–2343.

    Article  CAS  PubMed  Google Scholar 

  14. Worel N, Biener D, Kalhs P, Mitterbauer M, Keil F, Schulenburg A et al. Long-term outcome and quality of life of patients who are alive and in complete remission more than two years after allogeneic and syngeneic stem cell transplantation. Bone Marrow Transplant 2002; 30: 619–626.

    Article  CAS  PubMed  Google Scholar 

  15. Lee SJ, Kim HT, Ho VT, Cutler C, Alyea EP, Soiffer RJ et al. Quality of life associated with acute and chronic graft-versus-host disease. Bone Marrow Transplant 2006; 38: 305–310.

    Article  CAS  PubMed  Google Scholar 

  16. Fraser CJ, Bhatia S, Ness K, Carter A, Francisco L, Arora M et al. Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study. Blood 2006; 108: 2867–2873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kiss TL, Abdolell M, Jamal N, Minden MD, Lipton JH, Messner HA . Long-term medical outcomes and quality-of-life assessment of patients with chronic myeloid leukemia followed at least 10 years after allogeneic bone marrow transplantation. J Clin Oncol 2002; 20: 2334–2343.

    Article  CAS  PubMed  Google Scholar 

  18. Syrjala KL, Langer SL, Abrams JR, Storer BE, Martin PJ . Late effects of hematopoietic cell transplantation among 10-year adult survivors compared with case-matched controls. J Clin Oncol 2005; 23: 6596–6606.

    Article  PubMed  Google Scholar 

  19. Andrykowski MA, Greiner CB, Altmaier EM, Burish TG, Antin JH, Gingrich R et al. Quality of life following bone marrow transplantation: findings from a multicentre study. Br J Cancer 1995; 71: 1322–1329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Andrykowski MA, Henslee PJ, Barnett RL . Longitudinal assessment of psychosocial functioning of adult survivors of allogeneic bone marrow transplantation. Bone Marrow Transplant 1989; 4: 505–509.

    CAS  PubMed  Google Scholar 

  21. Bieri S, Roosnek E, Helg C, Verholen F, Robert D, Chapuis B et al. Quality of life and social integration after allogeneic hematopoietic SCT. Bone Marrow Transplant 2008; 42: 819–827.

    Article  CAS  PubMed  Google Scholar 

  22. Duell T, van Lint MT, Ljungman P, Tichelli A, Socie G, Apperley JF et al. Health and functional status of long-term survivors of bone marrow transplantation. EBMT Working Party on Late Effects and EULEP Study Group on Late Effects. European Group for Blood and Marrow Transplantation. Ann Intern Med 1997; 126: 184–192.

    Article  CAS  PubMed  Google Scholar 

  23. Yano K, Kanie T, Okamoto S, Kojima H, Yoshida T, Maruta I et al. Quality of life in adult patients after stem cell transplantation. Int J Hematol 2000; 71: 283–289.

    CAS  PubMed  Google Scholar 

  24. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  PubMed  Google Scholar 

  25. Ware Jr JE, Gandek B . Overview of the SF-36 health survey and the International Quality of Life Assessment (IQOLA) project. J Clin Epidemiol 1998; 51: 903–912.

    Article  PubMed  Google Scholar 

  26. Ware Jr JE, Kosinski M, Dewey JE . How to Score Version 2 of the SF-36 Health Survey. Quality Metric Incorporated: Lincoln, 2000.

    Google Scholar 

  27. McHorney CA, Ware Jr JE, Lu JF, Sherbourne CD . The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups. Med Care 1994; 32: 40–66.

    Article  CAS  PubMed  Google Scholar 

  28. McHorney CA, Ware Jr JE, Raczek AE . The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 1993; 31: 247–263.

    Article  CAS  PubMed  Google Scholar 

  29. Ware Jr JE, Sherbourne CD . The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: 473–483.

    Article  PubMed  Google Scholar 

  30. Ware Jr JE, Kosinski M, Bjorner JB, Turner-Bowker DM, Gandek B, Maruish ME . User's Manual for the SF-36v2 Health Survey, 2nd edn. Quality Metric Incorporated: Lincoln, RI, 2007.

    Google Scholar 

  31. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166: 111–117.

    Article  Google Scholar 

  32. Greene WB, Heckman JD . The Clinical Measurement of Joint Motion. American Academy of Orthopaedic Surgeons: Rosemont, IL, 1994.

    Google Scholar 

  33. Brooks D, Parsons J, Hunter JP, Devlin M, Walker J . The 2-min walk test as a measure of functional improvement in persons with lower limb amputation. Arch Phys Med Rehabil 2001; 82: 1478–1483.

    Article  CAS  PubMed  Google Scholar 

  34. Brooks D, Parsons J, Tran D, Jeng B, Gorczyca B, Newton J et al. The two-minute walk test as a measure of functional capacity in cardiac surgery patients. Arch Phys Med Rehabil 2004; 85: 1525–1530.

    Article  PubMed  Google Scholar 

  35. Bernstein ML, Despars JA, Singh NP, Avalos K, Stansbury DW, Light RW . Reanalysis of the 12-min walk in patients with chronic obstructive pulmonary disease. Chest 1994; 105: 163–167.

    Article  CAS  PubMed  Google Scholar 

  36. Beissner KL, Collins JE, Holmes H . Muscle force and range of motion as predictors of function in older adults. Phys Ther 2000; 80: 556–563.

    CAS  PubMed  Google Scholar 

  37. Lee S, Cook EF, Soiffer R, Antin JH . Development and validation of a scale to measure symptoms of chronic graft-versus-host disease. Biol Blood Marrow Transplant 2002; 8: 444–452.

    Article  PubMed  Google Scholar 

  38. Groll DL, To T, Bombardier C, Wright JG . The development of a comorbidity index with physical function as the outcome. J Clin Epidemiol 2005; 58: 595–602.

    Article  PubMed  Google Scholar 

  39. Groll DL, Heyland DK, Caeser M, Wright JG . Assessment of long-term physical function in acute respiratory distress syndrome (ARDS) patients: comparison of the Charlson Comorbidity Index and the Functional Comorbidity Index. Am J Phys Med Rehabil 2006; 85: 574–581.

    Article  PubMed  Google Scholar 

  40. Parimon T, Au DH, Martin PJ, Chien JW . A risk score for mortality after allogeneic hematopoietic cell transplantation. Ann Intern Med 2006; 144: 407–414.

    Article  PubMed  Google Scholar 

  41. Baron RM, Kenny DA . The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 1986; 51: 1173–1182.

    Article  CAS  PubMed  Google Scholar 

  42. Norman GR, Sloan JA, Wyrwich KW . Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care 2003; 41: 582–592.

    PubMed  Google Scholar 

  43. Dudley WN, Benuzillo JG, Carrico MS . SPSS and SAS programming for the testing of mediation models. Nurs Res 2004; 53: 59–62.

    Article  PubMed  Google Scholar 

  44. MacKinnon DP . Analysis of mediating variables in prevention and intervention research. NIDA Res Monogr 1994; 139: 127–153.

    CAS  PubMed  Google Scholar 

  45. Rovo A, Daikeler T, Stern M, Halter J, Studt JD, Buser A et al. Physical and not mental health is impaired in very long-term survivors after HSCT compared with their respective donors: a paired analysis. Blood 2008; 111: 1740–1741.

    Article  CAS  PubMed  Google Scholar 

  46. Extermann M, Overcash J, Lyman GH, Parr J, Balducci L . Comorbidity and functional status are independent in older cancer patients. J Clin Oncol 1998; 16: 1582–1587.

    Article  CAS  PubMed  Google Scholar 

  47. Kugler C, Fischer S, Gottlieb J, Tegtbur U, Welte T, Goerler H et al. Symptom experience after lung transplantation: impact on quality of life and adherence. Clin Transplant 2007; 21: 590–596.

    Article  PubMed  Google Scholar 

  48. Moons P, De Geest S, Abraham I, Cleemput JV, Van Vanhaecke J . Symptom experience associated with maintenance immunosuppression after heart transplantation: patients′ appraisal of side effects. Heart Lung 1998; 27: 315–325.

    Article  CAS  PubMed  Google Scholar 

  49. Kurtz ME, Kurtz JC, Stommel M, Given CW, Given BA . Symptomatology and loss of physical functioning among geriatric patients with lung cancer. J Pain Symptom Manage 2000; 19: 249–256.

    Article  CAS  PubMed  Google Scholar 

  50. Dodd MJ, Miaskowski C, Paul SM . Symptom clusters and their effect on the functional status of patients with cancer. Oncol Nurs Forum 2001; 28: 465–470.

    CAS  PubMed  Google Scholar 

  51. Given B, Given C, Azzouz F, Stommel M . Physical functioning of elderly cancer patients prior to diagnosis and following initial treatment. Nurs Res 2001; 50: 222–232.

    Article  CAS  PubMed  Google Scholar 

  52. Pavletic SZ, Martin P, Lee SJ, Mitchell S, Jacobsohn D, Cowen EW et al. Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. Response criteria working group report. Biol Blood Marrow Transplant 2006; 12: 252–266.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge Marjorie Pett, PhD, MSW, University of Utah College of Nursing, and N Lynn Gerber, MD, George Mason University, for advice and valuable critique of an early version of this manuscript, and Li Li, MD, National Institutes of Health, Clinical Center, Department of Rehabilitation Medicine, for assistance in obtaining the measures of functional capacity. The investigators wish to acknowledge all members of the National Institutes of Health cGVHD Clinic and Study Group, Bethesda, MD, for their expert care of these study participants and for assistance with data collection. We thank the two anonymous journal reviewers for their helpful critique. This work was supported by the National Institutes of Health, Clinical Center, Nursing and Patient Care Services.

Author information

Authors and Affiliations

  1. Nursing Research, Clinical Center, National Institutes of Health, Bethesda, MD, USA

    S A Mitchell, P Palit & M C Krumlauf

  2. Scientific Affairs, United BioSource Centre for Health Outcomes Research Corporation, Bethesda, MD, USA

    N Kline Leidy

  3. University of Utah, College of Nursing, Salt Lake City, UT, USA

    K H Mooney & S L Beck

  4. University of North Carolina-Greensboro, School of Health and Human Performance, Greensboro, NC, USA

    W N Dudley

  5. Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA

    P C LaStayo

  6. Dermatology Branch, National Cancer Institute, Bethesda, MD, USA

    E W Cowen

  7. Rehabilitation Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA

    L E Comis

  8. Experimental Transplant and Immunology Branch, National Cancer Institute, Bethesda, MD, USA

    D N Avila, D H Fowler & S Z Pavletic

  9. Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD, USA

    N Atlam

Authors
  1. S A Mitchell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Kline Leidy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K H Mooney
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W N Dudley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S L Beck
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P C LaStayo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E W Cowen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P Palit
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. L E Comis
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M C Krumlauf
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. D N Avila
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. N Atlam
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. D H Fowler
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. S Z Pavletic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S A Mitchell.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mitchell, S., Leidy, N., Mooney, K. et al. Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD). Bone Marrow Transplant 45, 762–769 (2010). https://doi.org/10.1038/bmt.2009.238

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.238

Keywords

This article is cited by

Search

Advanced search

Quick links