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Graft-Versus-Host Disease

Prevalence and determinants of fatigue in patients with moderate to severe chronic GvHD

Bone Marrow Transplantation volume 51, pages 705–712 (2016)Cite this article

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Abstract

Although fatigue is common after allogeneic hematopoietic cell transplantation, little is known about fatigue in patients with chronic GvHD (cGvHD). The aim of this study was to explore factors associated with fatigue in cGvHD. Data were drawn from a sequentially recruited, cross-sectional study of adults with moderate or severe cGvHD (n=263). Respondents were classified as fatigued or not fatigued based on their response to a single item regarding loss of energy from the Lee cGvHD Symptom Scale. In univariate analysis, factors significantly associated with fatigue included performance status, number of prior cGvHD therapies, cGvHD symptom bother, self-assessed physical and mental health, nutritional status, walk velocity and self-reported physical activity. There were no significant associations between fatigue and disease-related cGvHD variables. Multivariable logistic regression demonstrated that being less active and having pulmonary and/or muscle/joint symptoms were independently associated with fatigue. In conclusion, clinically significant fatigue was prevalent in more than one-third of subjects with cGvHD, and was disabling. Absence of association with measures of cGvHD severity underscores the need to elucidate the pathogenesis of fatigue and its relationship with inflammatory activity. Pulmonary and muscle/joint symptoms and physical inactivity represent potential targets for intervention in clinical studies.

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References

  1. Baird K, Pavletic SZ . Chronic graft versus host disease. Curr Opin Hematol 2006; 13: 426–435.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Pavletic SZ, Fowler DH . Are we making progress in GVHD prophylaxis and treatment? Hematology Am Soc Hematol Educ Program 2012; 2012: 251–264.

    PubMed  Google Scholar 

  4. Arai S, Arora M, Wang T, Spellman SR, He W, Courier DR et alGraft-vs-Host Disease Working Committee of the CIBMTR. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant 2015; 21: 266–274.

    Article  PubMed  Google Scholar 

  5. Dignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P et alHaemato-oncology Task Force of British Committee for Standards in Haematology British Society for Blood and Marrow Transplantation. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol 2012; 158: 46–61.

    Article  CAS  PubMed  Google Scholar 

  6. Dignan FL, Scarisbrick JJ, Cornish J, Clark A, Amrolia P, Jackson G et alHaemato-oncology Task Force of British Committee for Standards in Haematology British Society for Blood and Marrow Transplantation. Organ-specific management and supportive care in chronic graft-versus-host disease. Br J Haematol 2012; 158: 62–78.

    Article  CAS  PubMed  Google Scholar 

  7. Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn JY et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood 2002; 100: 406–414.

    Article  CAS  PubMed  Google Scholar 

  8. Boyiadzis M, Arora M, Klein J, Hassebroek A, Hemmer M, Urbano-Ispizua A et al. Impact of chronic graft-versus-host disease on late relapse and survival on 7489 patients after myeloablative allogeneic hematopoietic cell transplantation for leukemia. Clin Cancer Res 2014; 21: 2020–2028.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 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 

  10. 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 

  11. Hjermstad MJ, Knobel H, Brinch L, Fayers PM, Loge JH, Holte H et al. A prospective study of health-related quality of life, fatigue, anxiety and depression 3-5 years after stem cell transplantation. Bone Marrow Transplant 2004; 34: 257–266.

    Article  CAS  PubMed  Google Scholar 

  12. Andrykowski MA, Bishop MM, Hahn EA, Cella DF, Beaumont JL, Brady MJ et al. Long-term health-related quality of life, growth, and spiritual well-being after hematopoietic stem-cell transplantation. J Clin Oncol 2005; 23: 599–608.

    Article  PubMed  Google Scholar 

  13. Zordan R, Manitta V, Nandurkar H, Cole-Sinclair M, Philip J . Prevalence and predictors of fatigue in haemo-oncological patients. Intern Med J 2014; 44: 1013–1017.

    Article  CAS  PubMed  Google Scholar 

  14. Andrykowski MA, Carpenter JS, Greiner CB, Altmaier EM, Burish TG, Antin JH et al. Energy level and sleep quality following bone marrow transplantation. Bone Marrow Transplant 1997; 20: 669–679.

    Article  CAS  PubMed  Google Scholar 

  15. Gielissen MF, Schattenberg AV, Verhagen CA, Rinkes MJ, Bremmers ME, Bleijenberg G . Experience of severe fatigue in long-term survivors of stem cell transplantation. Bone Marrow Transplant 2007; 39: 595–603.

    Article  CAS  PubMed  Google Scholar 

  16. Mosher CE, DuHamel KN, Rini C, Corner G, Lam J, Redd WH . Quality of life concerns and depression among hematopoietic stem cell transplant survivors. Support Care Cancer 2011; 19: 1357–1365.

    Article  PubMed  Google Scholar 

  17. Lee SJ, Fairclough D, Parsons SK, Soiffer RJ, Fisher DC, Schlossman RL et al. Recovery after stem-cell transplantation for hematologic diseases. J Clin Oncol 2001; 19: 242–252.

    Article  CAS  PubMed  Google Scholar 

  18. Neitzert CS, Ritvo P, Dancey J, Weiser K, Murray C, Avery J . The psychosocial impact of bone marrow transplantation: a review of the literature. Bone Marrow Transplant 1998; 22: 409–422.

    Article  CAS  PubMed  Google Scholar 

  19. Leunis A, Redekop WK, Uyl-de Groot CA, Lowenberg B . Impaired health-related quality of life in acute myeloid leukemia survivors: a single-center study. Eur J Haematol 2014; 93: 198–206.

    Article  PubMed  Google Scholar 

  20. Mitchell SA, Leidy NK, Mooney KH, Dudley WN, Beck SL, LaStayo PC 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 2010; 45: 762–769.

    Article  CAS  PubMed  Google Scholar 

  21. 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 

  22. Pidala J, Anasetti C, Jim H . Quality of life after allogeneic hematopoietic cell transplantation. Blood 2009; 114: 7–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pallua S, Giesinger J, Oberguggenberger A, Kemmler G, Nachbaur D, Clausen J et al. Impact of GvHD on quality of life in long-term survivors of haematopoietic transplantation. Bone Marrow Transplant 2010; 45: 1534–1539.

    Article  CAS  PubMed  Google Scholar 

  24. Syrjala KL, Stover AC, Yi JC, Artherholt SB, Abrams JR . Measuring social activities and social function in long-term cancer survivors who received hematopoietic stem cell transplantation. Psychooncology 2010; 19: 462–471.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Bevans MF, Mitchell SA, Barrett JA, Bishop MR, Childs R, Fowler D et al. Symptom distress predicts long-term health and well-being in allogeneic stem cell transplantation survivors. Biol Blood Marrow Transplant 2014; 20: 387–395.

    Article  PubMed  Google Scholar 

  26. 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 

  27. Deschler B, Binek K, Ihorst G, Marks R, Wasch R, Bertz H et al. Prognostic factor and quality of life analysis in 160 patients aged>or =60 years with hematologic neoplasias treated with allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2010; 16: 967–975.

    Article  PubMed  Google Scholar 

  28. Berger AM, Mitchell SA . Cancer-related fatigue and sleep-wake disturbances. In Lester J, Schmitt P (eds). Cancer Rehabilitation and Survivorship: Transdisciplinary Approaches to Personalized Care. Oncology Nursing Society: Pittsburgh, PA, 2011 pp 101–112.

    Google Scholar 

  29. Berger AM, Mitchell SA, Jacobsen PB, Pirl WF . Screening, evaluation, and management of cancer-related fatigue: ready for implementation to practice? CA Cancer J Clin 2015; 65: 190–211.

    Article  PubMed  Google Scholar 

  30. Miller AH . Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behav Immun 2009; 23: 149–158.

    Article  CAS  PubMed  Google Scholar 

  31. Bower JE, Lamkin DM . Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications. Brain Behav Immun 2013; 30: S48–S57.

    Article  CAS  PubMed  Google Scholar 

  32. Winningham ML . Strategies for managing cancer-related fatigue syndrome: a rehabilitation approach. Cancer 2001; 92: 988–997.

    Article  CAS  PubMed  Google Scholar 

  33. Roscoe JA, Morrow GR, Hickok JT, Mustian KM, Shelke AR . Biobehavioral factors in chemotherapy-induced nausea and vomiting. J Natl Compr Canc Netw 2004; 2: 501–508.

    Article  PubMed  Google Scholar 

  34. Lee BN, Dantzer R, Langley KE, Bennett GJ, Dougherty PM, Dunn AJ et al. A cytokine-based neuroimmunologic mechanism of cancer-related symptoms. Neuroimmunomodulation 2004; 11: 279–292.

    Article  CAS  PubMed  Google Scholar 

  35. Ryan JL, Carroll JK, Ryan EP, Mustian KM, Fiscella K, Morrow GR . Mechanisms of cancer-related fatigue. Oncologist 2007; 12: 22–34.

    Article  CAS  PubMed  Google Scholar 

  36. Schubert C, Hong S, Natarajan L, Mills PJ, Dimsdale JE . The association between fatigue and inflammatory marker levels in cancer patients: a quantitative review. Brain Behav Immun 2007; 21: 413–427.

    Article  CAS  PubMed  Google Scholar 

  37. 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 

  38. Grkovic L, Baird K, Steinberg SM, Williams KM, Pulanic D, Cowen EW et al. Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity. Leukemia 2012; 26: 633–643.

    Article  CAS  PubMed  Google Scholar 

  39. Bauer J, Capra S, Ferguson M . Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. Eur J Clin Nutr 2002; 56: 779–785.

    Article  CAS  PubMed  Google Scholar 

  40. Jacobsohn DA, Margolis J, Doherty J, Anders V, Vogelsang GB . Weight loss and malnutrition in patients with chronic graft-versus-host disease. Bone Marrow Transplant 2002; 29: 231–236.

    Article  CAS  PubMed  Google Scholar 

  41. 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 

  42. McHorney CA, Ware JE Jr, 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 

  43. McHorney CA, Ware JE Jr, 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 

  44. Ware JE Jr, Kosinski M, Bjorner JB, Turner-Bowker DM, Gandek B, Maruish ME . Criterion-based Interpretation. In: User's Manual for the SF-36v2 Health Survey, 2nd edn. QualityMetric Incorporated: Lincoln, RI, 2007, pp 109–124.

    Google Scholar 

  45. Davidson M, de Morton N . A systematic review of the human activity profile. Clin Rehabil 2007; 21: 151–162.

    Article  PubMed  Google Scholar 

  46. Brown LF, Kroenke K, Theobald DE, Wu J . Comparison of SF-36 vitality scale and Fatigue Symptom Inventory in assessing cancer-related fatigue. Support Care Cancer 2011; 19: 1255–1259.

    Article  PubMed  Google Scholar 

  47. Donovan KA, Jacobsen PB, Small BJ, Munster PN, Andrykowski MA . Identifying clinically meaningful fatigue with the fatigue symptom inventory. J Pain Symptom Manage 2008; 36: 480–487.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Goedendorp MM, Jacobsen PB, Andrykowski MA . Fatigue screening in breast cancer patients: identifying likely cases of cancer-related fatigue. Psychooncology; e-pub ahead of print 22 July 2015; doi:10.1002/pon.3907.

  49. Bjorner JB, Wallenstein GV, Martin MC, Lin P, Blaisdell-Gross B, Tak Piech C et al. Interpreting score differences in the SF-36 Vitality scale: using clinical conditions and functional outcomes to define the minimally important difference. Curr Med Res Opin 2007; 23: 731–739.

    Article  PubMed  Google Scholar 

  50. Doro MP, Funke VA Sr, Neto JZ, Pelaez JM, Carvalho D, Maluf EC Sr et al. GVHD Impact on quality of life, health, sexuality, and fatigue of long term survivors after hematopoietic stem cell transplant. Biol Blood Marrow Transplant 2013; 19: S213.

    Article  Google Scholar 

  51. Jenkinson C, Coulter A, Wright L . Short form 36 (SF36) health survey questionnaire: normative data for adults of working age. BMJ 1993; 306: 1437–1440.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Mitchell SA, Hoffman AJ, Clark JC, DeGennaro RM, Poirier P, Robinson CB et al. Putting evidence into practice: an update of evidence-based interventions for cancer-related fatigue during and following treatment. Clin J Oncol Nurs 2014; 18: 38–58.

    Article  PubMed  Google Scholar 

  53. Brown LF, Kroenke K . Cancer-related fatigue and its associations with depression and anxiety: a systematic review. Psychosomatics 2009; 50: 440–447.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Nelson AM, Coe CL, Juckett MB, Rumble ME, Rathouz PJ, Hematti P et al. Sleep quality following hematopoietic stem cell transplantation: longitudinal trajectories and biobehavioral correlates. Bone Marrow Transplant 2014; 49: 1405–1411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Prieto JM, Blanch J, Atala J, Carreras E, Rovira M, Cirera E et al. Clinical factors associated with fatigue in haematologic cancer patients receiving stem-cell transplantation. Eur J Cancer 2006; 42: 1749–1755.

    Article  PubMed  Google Scholar 

  56. Jacobsen PB, Donovan KA, Weitzner MA . Distinguishing fatigue and depression in patients with cancer. Semin Clin Neuropsychiatry 2003; 8: 229–240.

    PubMed  Google Scholar 

  57. Saligan LN, Olson K, Filler K, Larkin D, Cramp F, Yennurajalingam S et alMultinational Association of Supportive Care in Cancer Fatigue Study Group-Biomarker Working Group. The biology of cancer-related fatigue: a review of the literature. Support Care Cancer 2015; 23: 2461–2478.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Pidala J, Sarwal M, Roedder S, Lee SJ . Biologic markers of chronic GVHD. Bone Marrow Transplant 2014; 49: 324–331.

    Article  CAS  PubMed  Google Scholar 

  59. Grulke N, Albani C, Bailer H . Quality of life in patients before and after haematopoietic stem cell transplantation measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire QLQ-C30. Bone Marrow Transplant 2012; 47: 473–482.

    Article  CAS  PubMed  Google Scholar 

  60. Butt Z, Wagner LI, Beaumont JL, Paice JA, Peterman AH, Shevrin D et al. Use of a single-item screening tool to detect clinically significant fatigue, pain, distress, and anorexia in ambulatory cancer practice. J Pain Symptom Manage 2008; 35: 20–30.

    Article  PubMed  Google Scholar 

  61. Kirsh KL, Passik S, Holtsclaw E, Donaghy K, Theobald D . I get tired for no reason: a single item screening for cancer-related fatigue. J Pain Symptom Manage 2001; 22: 931–937.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Funding was provided by the Intramural Research Program, National Cancer Institute and Center for Cancer Research.

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Authors and Affiliations

  1. Division of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    A Im

  2. Division of Cancer Control and Population Sciences, Outcomes Research Branch, National Cancer Institute, NIH, Rockville, MD, USA

    S A Mitchell

  3. Biostatistics and Data Management Section, Office of the Clinical Director, National Cancer Institute, NIH, Bethesda, MD, USA

    S M Steinberg

  4. Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA

    L Curtis, D Avila, L Masuch, F Pirsl & S Z Pavletic

  5. Pain and Palliative Care, Clinical Center, NIH, Bethesda, MD, USA

    A Berger

  6. Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, MD, USA

    K Baird

  7. Oncology/Hematology, Hospital Hietzing, Vienna, Austria

    Z Kuzmina

  8. Rehabilitation Medicine Department, NIH, Bethesda, MD, USA

    G Joe & L E Comis

  9. Division of Hematology and Medical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    M Juckett

  10. Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA

    J Baruffaldi

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Im, A., Mitchell, S., Steinberg, S. et al. Prevalence and determinants of fatigue in patients with moderate to severe chronic GvHD. Bone Marrow Transplant 51, 705–712 (2016). https://doi.org/10.1038/bmt.2015.320

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