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.

  • Article
  • Published:

Predictors of the trajectory of cognitive functioning in the first 6 months after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 55, pages 918–928 (2020)Cite this article

Subjects

Abstract

Certain subgroups of patients may be particularly vulnerable to cognitive decline after treatment with allogeneic hematopoietic stem cell transplant (HCT). The objective of this study was to identify predictors of cognitive functioning changes within the first 6 months after HCT. Fifty-eight adults treated with allogeneic HCT (53% male, mean 48 years of age) completed neuropsychological tests of learning/memory, psychomotor efficiency/processing speed, and executive functioning/working memory at three time points: pre-HCT and day 100 and 6 months post transplant. On average, there was significant improvement in learning/memory (p = 0.002), psychomotor efficiency/processing speed (p < 0.0001), and executive functioning/working memory (p < 0.0001), at 6 months. Multilevel modeling identified predictors of divergence from this trajectory; Karnofsky performance status <80 was associated with worsening learning/memory over time; peak severity of acute graft-versus-host disease >=Grade 2 was associated with worsening psychomotor efficiency/processing speed; and greater years of education predicted a faster improvement in psychomotor efficiency/processing speed. Other factors were associated with cognitive functioning over time: higher intelligence quotient (IQ) was associated with better cognitive functioning, and older age, being male, and greater pretransplant comorbidities were associated with worse cognitive functioning. Overall, cognitive performance appears to improve over the first 6 months after transplant. However, pretransplant and posttransplant factors may influence this trajectory.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Chang G, Meadows ME, Orav EJ, Antin JH. Mental status changes after hematopoietic stem cell transplantation. Cancer. 2009;115:4625–35.

    Article  PubMed  Google Scholar 

  2. Friedman MA, Fernandez M, Wefel JS, Myszka KA, Champlin RE, Meyers CA. Course of cognitive decline in hematopoietic stem cell transplantation: a within-subjects design. Arch Clin Neuropsychol. 2009;24:689–98.

    Article  PubMed  Google Scholar 

  3. Jacobs SR, Small BJ, Booth-Jones M, Jacobsen PB, Fields KK. Changes in cognitive functioning in the year after hematopoietic stem cell transplantation. Cancer. 2007;110:1560–7.

    Article  PubMed  Google Scholar 

  4. Sharafeldin N, Bosworth A, Patel SK, Chen Y, Morse E, Mather M, et al. Cognitive functioning after hematopoietic cell transplantation for hematologic malignancy: results from a prospective longitudinal study. J Clin Oncol. 2018;36:463–75.

    Article  CAS  PubMed  Google Scholar 

  5. Syrjala KL, Artherholt SB, Kurland BF, Langer SL, Roth-Roemer S, Elrod JB, et al. Prospective neurocognitive function over 5 years after allogeneic hematopoietic cell transplantation for cancer survivors compared with matched controls at 5 years. J Clin Oncol. 2011;29:2397–404.

  6. Syrjala KL, Dikmen S, Langer SL, Roth-Roemer S, Abrams JR. Neuropsychologic changes from before transplantation to 1 year in patients receiving myeloablative allogeneic hematopoietic cell transplant. Blood. 2004;104:3386–92.

    Article  CAS  PubMed  Google Scholar 

  7. Phillips KM, McGinty HL, Cessna J, Asvat Y, Gonzalez B, Cases MG, et al. A systematic review and meta-analysis of changes in cognitive functioning in adults undergoing hematopoietic cell transplantation. Bone Marrow Transpl. 2013;48:1350–7.

    Article  CAS  Google Scholar 

  8. Mayo S, Messner HA, Rourke SB, Howell D, Victor JC, Kuruvilla J, et al. Relationship between neurocognitive functioning and medication management ability over the first 6 months following allogeneic stem cell transplantation. Bone Marrow Transpl. 2016;51:841–7.

    Article  CAS  Google Scholar 

  9. Harder H, Cornelissen JJ, Van Gool AR, Duivenvoorden HJ, Eijkenboom WM, van den Bent MJ. Cognitive functioning and quality of life in long-term adult survivors of bone marrow transplantation. Cancer. 2002;95:183–92.

    Article  PubMed  Google Scholar 

  10. Braamse AM, van Meijel B, Visser O, Huijgens PC, Beekman AT, Dekker J. Distress, problems and supportive care needs of patients treated with auto- or allo-SCT. Bone Marrow Transpl. 2014;49:292–8.

    Article  CAS  Google Scholar 

  11. Wu LM, Austin J, Hamilton JG, Valdimarsdottir H, Isola L, Rowley S, et al. Self-efficacy beliefs mediate the relationship between subjective cognitive functioning and physical and mental well-being after hematopoietic stem cell transplant. Psycho-Oncol. 2012;21:1175–84.

    Article  Google Scholar 

  12. Jim HSL, Small B, Hartman S, Franzen J, Millay S, Phillips K, et al. Clinical predictors of cognitive function in adults treated with hematopoietic cell transplantation. Cancer. 2012;118:3407–16.

    Article  PubMed  Google Scholar 

  13. Scherwath A, Schirmer L, Kruse M, Ernst G, Eder M, Dinkel A, et al. Cognitive functioning in allogeneic hematopoietic stem cell transplantation recipients and its medical correlates: a prospective multicenter study. Psycho-Oncol. 2013;22:1509–16.

    Article  Google Scholar 

  14. Schulz-Kindermann F, Mehnert A, Scherwath A, Schirmer L, Schleimer B, Zander AR, et al. Cognitive function in the acute course of allogeneic hematopoietic stem cell transplantation for hematological malignancies. Bone Marrow Transpl. 2007;39:789–99.

    Article  CAS  Google Scholar 

  15. Hoogland AI, Nelson AM, Small BJ, Hyland KA, Gonzalez BD, Booth-Jones M, et al. The role of age in neurocognitive functioning among adult allogeneic hematopoietic cell transplant recipients. Biol Blood Marrow Transplant. 2017;23:1974–9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Harder H, Duivenvoorden HJ, van Gool AR, Cornelissen JJ, van den Bent MJ. Neurocognitive functions and quality of life in haematological patients receiving haematopoietic stem cell grafts: a one-year follow-up pilot study. J Clin Exp Neuropsychol. 2006;28:283–93.

    Article  PubMed  Google Scholar 

  17. Beglinger LJ, Duff K, Van Der Heiden S, Moser DJ, Bayless JD, Paulsen JS, et al. Neuropsychological and psychiatric functioning pre- and posthematopoietic stem cell transplantation in adult cancer patients: a preliminary study. J Int Neuropsychol Soc. 2007;13:172–7.

    Article  PubMed  Google Scholar 

  18. Fann JR, Alfano CM, Roth-Roemer S, Katon WJ, Syrjala KL. Impact of delirium on cognition, distress, and health-related quality of life after hematopoietic stem-cell transplantation. J Clin Oncol. 2007;25:1223–31.

    Article  PubMed  Google Scholar 

  19. Zerr DM, Fann JR, Breiger D, Boeckh M, Adler AL, Xie H, et al. HHV-6 reactivation and its effect on delirium and cognitive functioning in hematopoietic cell transplantation recipients. Blood. 2011;117:5243–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Meadows ME, Chang G, Jones JA, Antin JR, Orav EJ. Predictors of neuropsychological change in patients with chronic myelogenous leukemia and myelodysplastic syndrome. Arch Clin Neuropsychol. 2013;28:363–74.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wefel JS, Vardy J, Ahles T, Schagen SB. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol. 2011;12:703–8.

    Article  PubMed  Google Scholar 

  22. Heaton RK, Miller SW, Taylor MJ, Grant I. Revised comprehensive norms for an expanded halstead-reitan battery: demographically adjusted neuropsychological norms for African American and Caucasian Adults, professional manual. Lutz, FL: PAR; 2004.

    Google Scholar 

  23. Benedict RH, Schretlen D, Groninger L, Brandt J. Hopkins verbal learning test - revised: normative data and analysis of inter-form and test-retest reliability. Clin Neuropsychologist. 1998;12:43–65.

    Article  Google Scholar 

  24. Wechsler D. Wechsler adult intelligence scale - third edition: administration and scoring manual. San Antonio, TX: The Psychological Corporation; 1997.

    Google Scholar 

  25. Wechsler D. WMS-III: Wechsler memory scale administration and scoring manual. San Antonio, Texas: Psychological Corporation; 1997.

  26. The Neuropsychology Center. Manual for administration and scoring, trail making test. Plano, TX: The Neuropsychology Center; 2008.

    Google Scholar 

  27. Brandt J, Benedict RH. Hopkins verbal learning test - revised, professional manual. Lutz, FL: PAR; 2001.

    Google Scholar 

  28. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sorror ML. Comorbidities and hematopoietic cell transplantation outcomes. Hematol Am Soc Hematol Educ Program. 2010;2010:237–47.

    Article  Google Scholar 

  30. Sorror ML. How I assess comorbidities before hematopoietic cell transplantation. Blood. 2013;121:2854–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lezak MD, Howieson DB, Loring DW. Neuropsychological assessment. 4th ed. New York: Oxford University Press; 2004.

  32. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transpl. 1995;15:825–8.

    CAS  Google Scholar 

  33. 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;11:945–56.

    Article  PubMed  Google Scholar 

  34. Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM, editor. Evaluation of chemotherapeutic agents; symposium held at the New York Academy of Medicine, Mar 25 and 26, 1948. New York: Columbia University Press; 1949. 196.

  35. Portenoy RK, Thaler HT, Kornblith AB, Lepore JM, Friedlander-Klar H, Kiyasu E, et al. The Memorial symptom assessment scale: an instrument for the evaluation of symptom prevalence, characteristics and distress. Eur J Cancer. 1994;30A:1326–36.

    Article  CAS  PubMed  Google Scholar 

  36. Chang VT, Hwang SS, Feuerman M, Kasimis BS, Thaler HT. The Memorial symptom assessment scale short form (MSAS-SF). Cancer. 2000;89:1162–71.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  38. Radloff LS. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychological Meas. 1977;1:385–401.

    Article  Google Scholar 

  39. Singer JD, Willett JB. Applied longitudinal data analysis: modeling change and event occurrence. New York: Oxford University Press; 2003.

    Book  Google Scholar 

  40. Booth-Jones M, Jacobsen PB, Ransom S, Soety E. Characteristics and correlates of cognitive functioning following bone marrow transplantation. Bone Marrow Transpl. 2005;36:695–702.

    Article  CAS  Google Scholar 

  41. Sorror ML, Storer B, Sandmaier BM, Maloney DG, Chauncey TR, Langston A, et al. Hematopoietic cell transplantation-comorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation. Cancer. 2008;112:1992–2001.

    Article  PubMed  Google Scholar 

  42. Kleinbaum DG, Klein M, Pryor ER. Logistic regression: a self-learning text. 3rd ed. New York: Springer; 2010.

  43. Montgomery DC, Peck EA, Vining GG. Introduction to linear regression analysis. 4th ed. Hoboken, N.J.: Wiley-Interscience; 2006.

  44. Rosner B. Fundamentals of biostatistics. 6th ed. Belmont, CA: Thomson-Brooks/Cole; 2006.

  45. Correa DD, Root JC, Baser R, Moore D, Peck KK, Lis E, et al. A prospective evaluation of changes in brain structure and cognitive functions in adult stem cell transplant recipients. Brain Imaging Behav. 2013;7:478–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Panza F, Frisardi V, Capurso C, Imbimbo BP, Vendemiale G, Santamato A, et al. Metabolic syndrome and cognitive impairment: current epidemiology and possible underlying mechanisms. J Alzheimers Dis. 2010;21:691–724.

    Article  PubMed  Google Scholar 

  47. Shelton BK. Neurologic complications of hematopoietic stem cell transplantation. In: Ezzone S, Schmit-Pokorny K, editors. Blood and marrow stem cell transplantation: principles, practice, and nursing insights. 3rd ed. Sudbury, Mass.: Jones and Bartlett Publishers; 2007. 297-325.

  48. Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009;373:1550–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sostak P, Padovan CS, Yousry TA, Ledderose G, Kolb HJ, Straube A. Prospective evaluation of neurological complications after allogeneic bone marrow transplantation. Neurology. 2003;60:842–8.

    Article  CAS  PubMed  Google Scholar 

  50. Levy MR, Fann JR. The neuropsychiatry of hematopoietic stem cell transplantation. Eur J Psychiatry. 2006;20:107–28.

    Article  Google Scholar 

  51. Hoodin F, LaLonde L, Errickson J, Votruba K, Kentor R, Gatza E, et al. Cognitive function and quality of life in vorinostat-treated patients after matched unrelated donor myeloablative conditioning hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2019;25:343–53.

    Article  CAS  PubMed  Google Scholar 

  52. Ahles TA, Saykin AJ, McDonald BC, Li Y, Furstenberg CT, Hanscom BS, et al. Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol. 2010;28:4434–40.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Howieson DB, Loring DW, Hannay HJ. Neurobehavioural variables and diagnostic issues. In: Lezak MD, Howieson DB, Loring DW, editors. Neuropsychological assessment. 4th ed. New York: Oxford University Press; 2004. p. 286-334.

  54. Stern Y. What is cognitive reserve? Theory and research application of the reserve concept. J Int Neuropsychol Soc. 2002;8:448–60.

    Article  PubMed  Google Scholar 

  55. Sumowski JF. Cognitive reserve as a useful concept for early intervention research in multiple sclerosis. Front Neurol. 2015;6:176.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Cody SL, Vance DE. The neurobiology of HIV and its impact on cognitive reserve: a review of cognitive interventions for an aging population. Neurobiol Dis. 2016;92:144–56.

    Article  PubMed  Google Scholar 

  57. Whalley LJ, Deary IJ, Appleton CL, Starr JM. Cognitive reserve and the neurobiology of cognitive aging. Ageing Res Rev. 2004;3:369–82.

    Article  PubMed  Google Scholar 

  58. Ahles TA, Root JC, Ryan EL. Cancer- and cancer treatment–associated cognitive change: an update on the state of the science. J Clin Oncol. 2012;30:3675–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kelly DL, Buchbinder D, Duarte RF, Auletta JJ, Bhatt N, Byrne M, et al. Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and complications and quality of Life Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2018;24:228–41.

    Article  PubMed  Google Scholar 

  60. Gladsjo JA, Schuman CC, Evans JD, Peavy GM, Miller SW, Heaton RK. Norms for letter and category fluency: demographic corrections for age, education, and ethnicity. Assessment. 1999;6:147–78.

    Article  CAS  PubMed  Google Scholar 

  61. Strauss E, Spreen O, Sherman EMS, Spreen O. A compendium of neuropsychological tests: administration, norms, and commentary. 3rd ed. Oxford: Oxford University Press; 2006.

Download references

Acknowledgements

This work was funded by the Fred Banting and Charles Best Canada Graduate Scholarship—Doctoral Award, Canadian Institutes of Health Research (SJM), and the Rosenstadt Dissertation Award, Lawrence S. Bloomberg Faculty of Nursing, University of Toronto (SJM).

Author information

Author notes

  1. Deceased: Hans A. Messner

Authors and Affiliations

  1. Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada

    Samantha J. Mayo, Doris Howell & Kelly Metcalfe

  2. Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

    Samantha J. Mayo, Hans A. Messner, Doris Howell, Jeffrey H. Lipton, J. Kuruvilla, Vikas Gutpa, Dennis Dong Hwan Kim & Fotios V. Michelis

  3. MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada

    Sean B. Rourke

  4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Sean B. Rourke

  5. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada

    J. Charles Victor

  6. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Jeffrey H. Lipton, J. Kuruvilla, Vikas Gutpa, Dennis Dong Hwan Kim & Fotios V. Michelis

  7. Women’s College Research Institute, Toronto, ON, Canada

    Kelly Metcalfe

Authors
  1. Samantha J. Mayo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hans A. Messner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sean B. Rourke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Doris Howell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Charles Victor
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jeffrey H. Lipton
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Kuruvilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vikas Gutpa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dennis Dong Hwan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fotios V. Michelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kelly Metcalfe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samantha J. Mayo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics

This study was conducted in accordance with the Declaration of Helsinki and with approval from the Research Ethics Boards of the University Health Network (#11-0994-CE) and the University of Toronto (#27495).

Informed consent

Informed consent was obtained from all participants.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mayo, S.J., Messner, H.A., Rourke, S.B. et al. Predictors of the trajectory of cognitive functioning in the first 6 months after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 55, 918–928 (2020). https://doi.org/10.1038/s41409-019-0746-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-019-0746-3

This article is cited by

Search

Advanced search

Quick links