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Correlates of fatigue severity in patients with chronic myeloid leukemia treated with targeted therapy

Supportive Care in Cancer volume 30, pages 87–94 (2022)Cite this article

Abstract

Purpose

Tyrosine kinase inhibitors (TKIs) substantially improve survival for patients with chronic myeloid leukemia (CML), but fatigue associated with TKIs can negatively impact patients’ quality of life and adherence. This study sought to identify correlates of fatigue (e.g., sociodemographic characteristics, clinical characteristics, health behaviors) among patients with CML taking TKIs who reported moderate to severe fatigue.

Methods

Adults with CML experiencing at least moderate fatigue were recruited for a pilot trial of a cognitive behavioral intervention to improve fatigue. Data collected pre-intervention were used to explore concurrent correlates of fatigue in univariate and multivariable models.

Results

Participants (N = 44, 48% female) were M = 55.6 years old (SD = 12.6) and had been diagnosed with CML M = 5.2 years prior (SD = 5.3). Participants had been taking their current TKI for M = 2.5 years (SD = 2.7). Most participants (64%) had previously been treated with ≥ 1 other TKI. More than three-quarters of participants (77%) reported severe fatigue. In univariate models, worse fatigue was associated with higher BMI (r = -0.36, p = 0.018), prior treatment with other TKI(s) (r =  − 0.34, p = 0.024), worse sleep disturbance (r =  − 0.51, p < 0.001), and less physical activity (r = 0.31, p = 0.043). In a multivariable model, significant univariate correlates accounted for 39% of the variance in fatigue. Worse fatigue remained significantly correlated with higher BMI (β =  − 0.33, p = 0.009) and more disturbed sleep (β =  − 0.45, p < 0.001).

Conclusion

Results may inform future research aiming to identify fatigued patients with CML at risk for experiencing more severe fatigue during TKI therapy. Identifying predictors of fatigue severity could aid clinicians in identifying which patients will benefit from referrals to supportive therapy.

Trial registration: NCT02592447, October 30, 2015

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

References

  1. Kantarjian H, O’Brien S, Jabbour E, Garcia-Manero G, Quintas-Cardama A, Shan J et al (2012) Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood 119(9):1981–1987

    CAS  Article  Google Scholar 

  2. Flynn KE, Atallah E (2016) Quality of life and long-term therapy in patients with chronic myeloid leukemia. Curr Hematol Malig Rep 11(2):80–85

    Article  Google Scholar 

  3. Jacobs JM, Ream ME, Pensak N, Nisotel LE, Fishbein JN, MacDonald JJ et al (2019) Patient experiences with oral chemotherapy: adherence, symptoms, and quality of life. J Natl Compr Canc Netw 17(3):221–228

    Article  Google Scholar 

  4. Efficace F, Baccarani M, Breccia M, Alimena G, Rosti G, Cottone F et al (2011) Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood 118(17):4554–4560

    CAS  Article  Google Scholar 

  5. Efficace F, Baccarani M, Rosti G, Cottone F, Castagnetti F, Breccia M et al (2012) Investigating factors associated with adherence behaviour in patients with chronic myeloid leukemia: an observational patient-centered outcome study. Br J Cancer 107(6):904–909

    CAS  Article  Google Scholar 

  6. Williams LA, Garcia Gonzalez AG, Ault P, Mendoza TR, Sailors ML, Williams JL et al (2013) Measuring the symptom burden associated with the treatment of chronic myeloid leukemia. Blood 122(5):641–647

    CAS  Article  Google Scholar 

  7. Phillips KM, Pinilla-Ibarz J, Sotomayor E, Lee MR, Jim HS, Small BJ et al (2013) Quality of life outcomes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a controlled comparison. Support Care Cancer 21(4):1097–1103

    Article  Google Scholar 

  8. Janssen L, Blijlevens NMA, Drissen MMCM, Bakker EA, Nuijten MAH, Janssen JJWM et al (2021) Fatigue in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy: predictors and the relationship with physical activity. Haematologica 106(7):1876–1882

  9. Efficace F, Baccarani M, Breccia M, Cottone F, Alimena G, Deliliers GL et al (2013) Chronic fatigue is the most important factor limiting health-related quality of life of chronic myeloid leukemia patients treated with imatinib. Leukemia 27(7):1511–1519

    CAS  Article  Google Scholar 

  10. Efficace F, Castagnetti F, Martino B, Breccia M, D’Adda M, Angelucci E et al (2018) Health-related quality of life in patients with chronic myeloid leukemia receiving first-line therapy with nilotinib. Cancer 124(10):2228–2237

    CAS  Article  Google Scholar 

  11. Efficace F, Rosti G, Aaronson N, Cottone F, Angelucci E, Molica S et al (2014) Patient- versus physician-reporting of symptoms and health status in chronic myeloid leukemia. Haematologica 99(4):788–793

    Article  Google Scholar 

  12. Peoples AR, Roscoe JA, Block RC, Heckler CE, Ryan JL, Mustian KM et al (2017) Nausea and disturbed sleep as predictors of cancer-related fatigue in breast cancer patients: a multicenter NCORP study. Support Care Cancer 25(4):1271–1278

    Article  Google Scholar 

  13. Bevilacqua LA, Dulak D, Schofield E, Starr TD, Nelson CJ, Roth AJ et al (2018) Prevalence and predictors of depression, pain, and fatigue in older- versus younger-adult cancer survivors. Psychooncology 27(3):900–907

    Article  Google Scholar 

  14. Thong MSY, Mols F, van de Poll-Franse LV, Sprangers MAG, van der Rijt CCD, Barsevick AM et al (2018) Identifying the subtypes of cancer-related fatigue: results from the population-based PROFILES registry. J Cancer Surviv 12(1):38–46

    Article  Google Scholar 

  15. Nelson AM, Gonzalez BD, Jim HS, Cessna JM, Sutton SK, Small BJ et al (2016) Characteristics and predictors of fatigue among men receiving androgen deprivation therapy for prostate cancer: a controlled comparison. Support Care Cancer 24(10):4159–4166

    Article  Google Scholar 

  16. de Jong N, Courtens AM, Abu-Saad HH, Schouten HC (2002) Fatigue in patients with breast cancer receiving adjuvant chemotherapy: a review of the literature. Cancer Nurs 25(4):283–97 (quiz 98-9)

    Article  Google Scholar 

  17. Jim HSL, Hyland KA, Nelson AM, Pinilla-Ibarz J, Sweet K, Gielissen M et al (2020) Internet-assisted cognitive behavioral intervention for targeted therapy-related fatigue in chronic myeloid leukemia: results from a pilot randomized trial. Cancer 126(1):174–180

    Article  Google Scholar 

  18. Center for Disease Control and Prevention. About Adult BMI 2020 [Available from: https://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/index.html. Accessed 3 Aug 2020

  19. Cella D (1997) The Functional Assessment of Cancer Therapy-Anemia (FACT-An) Scale: a new tool for the assessment of outcomes in cancer anemia and fatigue. Semin Hematol 34(3 Suppl 2):13–19

    CAS  PubMed  Google Scholar 

  20. Eek D, Ivanescu C, Kool-Houweling L, Cella D (2019) Psychometric Evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue) in patients with chronic lymphocytic leukemia (CLL). American Society of Hematology, Washington DC

    Book  Google Scholar 

  21. Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A et al (1993) The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol 11(3):570–579

    CAS  Article  Google Scholar 

  22. Victorson D, Barocas J, Song J, Cella D (2008) Reliability across studies from the functional assessment of cancer therapy-general (FACT-G) and its subscales: a reliability generalization. Qual Life Res 17(9):1137–1146

    Article  Google Scholar 

  23. Ditre JW, Gonzalez BD, Simmons VN, Faul LA, Brandon TH, Jacobsen PB (2011) Associations between pain and current smoking status among cancer patients. Pain 152(1):60–65

    Article  Google Scholar 

  24. Bergner M, Bobbitt RA, Pollard WE, Martin DP, Gilson BS (1976) The sickness impact profile: validation of a health status measure. Med Care 14(1):57–67

    CAS  Article  Google Scholar 

  25. Bergner M, Bobbitt RA, Carter WB, Gilson BS (1981) The sickness impact profile: development and final revision of a health status measure. Med Care 19(8):787–805

    CAS  Article  Google Scholar 

  26. Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE et al (2003) International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 35(8):1381–1395

    Article  Google Scholar 

  27. Lee PH, Macfarlane DJ, Lam TH, Stewart SM (2011) Validity of the International Physical Activity Questionnaire Short Form (IPAQ-SF): a systematic review. Int J Behav Nutr Phys Act 8:115

    Article  Google Scholar 

  28. Forde C. Scoring the International Physical Activity Questionnaire (IPAQ): Trinity College Dublin; [Available from: https://ugc.futurelearn.com/uploads/files/bc/c5/bcc53b14-ec1e-4d90-88e3-1568682f32ae/IPAQ_PDF.pdf. Accessed 3 Aug 2020

  29. SEER*Explorer: An interactive website for SEER cancer statistics [Internet]: Surveillance Research Program, National Cancer Institute; [Available from: https://seer.cancer.gov/explorer/. Accessed 3 Aug 2020

  30. Yellen SB, Cella DF, Webster K, Blendowski C, Kaplan E (1997) Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain Symptom Manage 13(2):63–74

    CAS  Article  Google Scholar 

  31. Cella D, Eton DT, Lai JS, Peterman AH, Merkel DE (2002) Combining anchor and distribution-based methods to derive minimal clinically important differences on the Functional Assessment of Cancer Therapy (FACT) anemia and fatigue scales. J Pain Symptom Manage 24(6):547–561

    Article  Google Scholar 

  32. Brucker PS, Yost K, Cashy J, Webster K, Cella D (2005) General population and cancer patient norms for the Functional Assessment of Cancer Therapy-General (FACT-G). Eval Health Prof 28(2):192–211

    Article  Google Scholar 

  33. Webster K, Cella D, Yost K (2003) The Functional Assessment of Chronic Illness Therapy (FACIT) measurement system: properties, applications, and interpretation. Health Qual Life Outcomes 1:79

    Article  Google Scholar 

  34. Yost KJ, Eton DT (2005) Combining distribution- and anchor-based approaches to determine minimally important differences: the FACIT experience. Eval Health Prof 28(2):172–191

    Article  Google Scholar 

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Funding

This study was funded by the National Cancer Institute (R21-CA191594 and P30-CA076292); the views expressed are those of the authors and do not necessarily represent those of the National Cancer Institute. This work was also supported in part by the Population Research, Interventions, and Measurement Core Facility at the H. Lee Moffitt Cancer Center and Research Institute, a National Cancer Institute-designated comprehensive cancer center.

Author information

Authors and Affiliations

  1. Department of Health Outcomes and Behavior, Moffitt Cancer Center, 12902 Magnolia Dr., MRC-SCM, Tampa, FL, 33612, USA

    Laura B. Oswald, Sarah L. Eisel, Aasha I. Hoogland & Heather S. L. Jim

  2. Department of Psychology, University of South Florida, Tampa, FL, USA

    Kelly A. Hyland

  3. Department of Medical Psychology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands

    Hans Knoop

  4. Department of Psychiatry, Harvard Medical School/Massachusetts General Hospital, Boston, MA, USA

    Ashley M. Nelson

  5. Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL, USA

    Javier Pinilla-Ibarz & Kendra Sweet

  6. Division of Cancer Control and Population Science, National Cancer Institute, Bethesda, MD, USA

    Paul B. Jacobsen

Authors
  1. Laura B. Oswald
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  2. Kelly A. Hyland
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  3. Sarah L. Eisel
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  4. Aasha I. Hoogland
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  5. Hans Knoop
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  6. Ashley M. Nelson
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  7. Javier Pinilla-Ibarz
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  8. Kendra Sweet
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  9. Paul B. Jacobsen
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  10. Heather S. L. Jim
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Contributions

LBO: conceptualization, writing-original draft, writing-review and editing; KAH: formal analysis, data curation, writing-original draft, writing-review and editing; SLE: formal analysis, data curation, writing-original draft, writing-review and editing; AIH: data curation, writing-original draft, writing-review and editing; HK: writing-review and editing; AMN: writing-review and editing; JP-I: writing-review and editing; KS: writing-review and editing; PBJ: conceptualization, writing-review and editing, funding acquisition; HSLJ: conceptualization, writing-review and editing, funding acquisition.

Corresponding author

Correspondence to Laura B. Oswald.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Chesapeake Institutional Review Board (Pro00023476).

Consent to participate

Informed consent to participate was obtained from all individual participants included in this study.

Consent to publish

All participants consented to having de-identified and aggregate study data published.

Conflicts of interest

Dr. Jim is a paid consultant for RedHill BioPharma, Janssen Scientific Affairs, and Merck. The other authors have no relevant conflicts of interest.

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Oswald, L.B., Hyland, K.A., Eisel, S.L. et al. Correlates of fatigue severity in patients with chronic myeloid leukemia treated with targeted therapy. Support Care Cancer 30, 87–94 (2022). https://doi.org/10.1007/s00520-021-06408-1

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  • DOI: https://doi.org/10.1007/s00520-021-06408-1

Keywords

  • Chronic myeloid leukemia
  • Fatigue
  • Health behavior
  • Psycho-oncology
  • Quality of life