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Allogeneic transplant survivors at increased risk for cognitive decline
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Patients who underwent allogeneic transplantation demonstrated significantly higher risk for cognitive impairment after transplant than healthy controls, according to results from a prospective, longitudinal study.
“A significant population of allogeneic transplant survivors will experience cognitive impairment that can impact different aspects of their lives,” Noha Sharafeldin, MD, MSc, PhD, instructor in the division of hematology and oncology at The University of Alabama at Birmingham and at The University of Alabama at Birmingham’s Institute for Cancer Outcomes and Survivorship, said in a press release. “It is critical that we as clinicians develop interventions for these patients. This research is just the beginning of our figuring out how we can best care for transplant survivors and enable them to live healthy lives.”
Sharafeldin and colleagues assessed the prevalence of cognitive impairment among 477 patients who underwent allogeneic blood or marrow transplantation at City of Hope between 2004 and 2014.
Patients received standardized neuropsychological testing that covered eight cognitive domains: executive function, verbal fluency and speed, processing speed, working memory, visual and auditory memory, and fine motor dexterity. Patients underwent testing before transplant, as well as 6 months, 1 year, 2 years and 3 years after transplant.
Researchers compared results from transplant recipients with those of 99 healthy matched controls.
More than one-third (35.7%) of patients who underwent allogeneic transplant showed evidence of cognitive decline at 3 years after transplant. In addition, an analysis of allogeneic transplant recipients who remained on study at the 3-year mark showed 38% had not returned to work. Recipients who experienced cognitive impairment appeared 10 times more likely not to return to work as those who did not develop cognitive impairment.
“It is clear that we have to make strides in supporting allogeneic transplant recipients in their recovery to ensure that we are educating patients and their families on signs of cognitive impairment,” Sharafeldin said in the release. “These data will help us identify patients at highest risk for cognitive impairment and inform the development of interventions that facilitate a patient’s recovery and return to normal life.”
HemOnc Today spoke with Sharafeldin about the importance of this study, the implications of the results, and what must be addressed in subsequent research.
Question: How did the idea for this study come about?
Answer: The study was conceived by Smita Bhatia, MD, MPH, during her tenure as chair of population sciences at City of Hope. The purpose was to better understand the impact of transplant on the cognitive outcomes among blood cancer survivors. Prior to this study, there were limitations in the literature, including insufficient follow-up of patients after transplantation. Also, previous studies had not examined cognitive functioning prior to transplant, and not all studies evaluated cognitive function in a standardized way. Most importantly, none of the previous studies had used a concurrently studied cohort of healthy individuals as a comparison group. Our study addressed all of these limitations.
Q: What did you find?
A: The main finding was that 36% of the patients who underwent an allogeneic bone marrow transplantation showed evidence of cognitive decline 3 years after transplant. Patients who received full-intensity treatment for their allogeneic transplant were most comprised; their odds of developing cognitive impairment was 3.5 times greater compared with healthy controls. Allogeneic transplant recipients who received reduced-intensity treatment were comparable to healthy controls overall; however, they did show some evidence of delayed decline at the 3-year time point. Autologous transplant recipients were generally spared. We also found older age, male sex, lower socioeconomic status and lower cognitive reserve were associated with cognitive decline. Transplant recipients with global cognitive impairment were 10 times more likely to not return to work compared with those who did not show cognitive decline after transplant.
Q: Did any of the findings surprise you?
A: Based upon the literature that was available at the time we conducted the study, there was some indication that patients who received full-intensity allogeneic transplant were at higher risk for cognitive decline after transplant. Yet, the trajectory for cognitive performance for reduced intensity was not clear. Also surprising was the finding that patients with global cognitive impairment were much less likely to return to work after transplant, which indicates that cognitive impairment is an important barrier for those patients.
Q: What are the clinical implications of these findings?
A: Oncologists and survivors increasingly recognize cognitive impairment as a cancer treatment-related outcome. Clinicians may consider discussing the potential for cognitive decline after transplant upfront. We also think clinicians should objectively assess patients’ cognitive function after transplant, especially if survivors are voicing concerns about cognitive issues.
Q: What will subsequent research on this topic address ?
A: We think more research is needed to better define who exactly is at higher risk for cognitive decline and also better define the appropriate recommendations for these patients before we can implement them in practice. DNA was collected from study participants, and we are using this resource to identify genetic factors that are associated with cognitive impairment after transplantation. We also are using the genetic information — together with the demographic and clinical characteristics — to construct risk-prediction models that will help us to identify patients at higher risk for cognitive decline. On the intervention side, we are conducting a pilot study to assess the feasibility of a cognitive training intervention.
Q : Do you have anything else that you would like to mention ?
A: I would like to acknowledge all of the other authors who worked on this project from inception. It takes many years to conduct a project, and many people to do this.
The study was conducted at City of Hope under the lead of Smita Bhatia, MD, MPH. In addition, Yanjun Chen, MS, and Lennie F. Wong, PhD, also worked the analysis; Alysia Bosworth, BA, conducted the cognitive testing portion; Sunita K. Patel, PhD, served as the lead neuropsychologist; and Stephen Forman, MD, was a strong and steadfast proponent of the study. – by Jennifer Southall
Reference:
Sharafeldin N, et al. J Clin Oncol. 2018;doi:10.1200/JCO.2017.74.2270.
For more information:
Noha Sharafeldin, MD, MSc, PhD, can be reached at The University of Alabama at Birmingham, Lowder 500, 1600 7th Ave. South, Birmingham, AL 35233; email: nsharafeldin@peds.uab.edu.
Disclosures: The study was funded by the Leukemia and Lymphoma Society. Sharafeldin reports no relevant financial disclosures.