The long-term impact of neurocognitive impairment after transplant

From the Chow Group, Clinical Research Division

Long-term survival after hematopoietic cell transplant has improved greatly due to advancements in transplant practice and care. Despite this, transplant recipients are a high-risk group for issues related to neurocognitive function – a term used to describe a wide-range of neurocognitive impairments such as difficulties with memory – which can contribute to a reduced quality of life for this population. While previous research efforts have noted the increased risk of neurocognitive impairments in this population, it remains an understudied area particularly with respect to long-term follow up of transplant survivors. To address this, during her hematology oncology fellowship at Fred Hutch, Dr. Natalie Wu (now an Assistant Professor of Pediatrics at University of California, San Francisco) led a research study with colleagues under the guidance of Dr. Eric Chow, a member of Fred Hutch’s Clinical Research Division, that aimed to determine the impact of neurocognitive impairments on the transplant community. The authors focused their research, recently published in Blood Advances, on long-term adult survivors of hematopoietic cell transplant. Describing the goals and primary outcomes of their study, Dr. Wu explains “we know that impairments in neurocognitive function can impact the post-transplant course and overall quality of life. However, there have been limited studies on neurocognitive outcomes in long-term survivors of stem cell transplant. In this work utilizing data from the Fred Hutch Long-Term Follow-Up cohort, survivors reported an overall quality of life comparable with the general population, although they also reported persistent impairments in specific neurocognitive domains, such as memory and organization.” The present study builds on their previous research examining long-term neurocognitive outcomes in pediatric transplant recipients (published in Journal of Cancer Survivorship).

As highlighted by Dr. Wu, the authors were able to undertake this study with support from the Fred Hutch Long-term Follow-Up cohort, a program that enables continuous long-term follow-up of transplant recipients dating back to the first transplant procedure performed in 1971. The program sends annual surveys to all consenting recipients of a transplant at Fred Hutchinson Cancer Center, and the authors were able to adapt these surveys to include validated instruments that assessed neurocognitive function and associated quality of life among participants. This allowed for their study to reach a wide range of transplant recipients, cumulating in 1861 people taking part. 

Hearing problems and difficulties with sleep are associated with reduced quality of life in hematopoietic cell transplant recipients.
Hearing problems and difficulties with sleep are associated with reduced quality of life in hematopoietic cell transplant recipients. Image provided by Dr. Wu.

The authors note that adult transplant recipients reported average neurocognitive quality of life scores when compared to the general non-transplant population. Interestingly, the authors report that older transplant survivors described higher cognitive quality of life scores when compared to younger survivors, a finding that remained constant and was independently correlated with improved cognitive quality of life in adjusted multivariable regression analyses. The authors next divided the study population into two sub-groups – those who received an allogenic transplant (stem cells from a donor) and those who received an autologous transplant (patient’s own cells). The two subgroups reported similar outcomes albeit at different frequencies, with both describing issues with task efficiency, memory, and organization. Transplant survivors who had a history of stroke, seizure or hearing difficulties were also more likely to report reduced neurocognitive quality of life scores. Further, hearing issues and disrupted sleep were associated with poorer neurocognitive quality of life scores in both groups, with sleep issues being linked to the majority of neurocognitive impairment domains in both allogenic and autologous transplant survivors.

The authors are working towards utilizing the findings from this study to inform future interventions that address issues faced by the post-transplant community, with the goal of improving overall quality of life. “Studies like ours can potentially help providers identify vulnerable populations at higher risk for post-transplant neurocognitive dysfunction. For example, we found that certain subsets of survivors, including those with hearing issues, were more likely to report lower quality of life and neurocognitive dysfunction. For us, one of the more notable results was the strong association of impaired sleep with poor neurocognitive outcomes, which highlights the importance of early identification and development of interventions for sleep issues,” detailed Dr. Wu. 

This work was supported by funding from the National Institutes of Health and a T32 training grant.

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Dr. Amanda Phipps, Dr. Karen Syrjala, Dr. Paul Carpenter, Dr. Laura Connelly-Smith, Dr. Mary Flowers, Dr. Elizabeth Krakow, Dr. Masumi Ueda Oshima, Dr. Stephanie Lee and Dr. Eric Chow contributed to this work.

Wu NL, Phipps AI, Krull KR, Syrjala KL, Carpenter PA, Connelly-Smith L, Flowers ME, Krakow EF, Ueda Oshima M, Lee SJ, Chow EJ. Long-term patient-reported neurocognitive outcomes in adult survivors of hematopoietic cell transplant. Blood Adv. 2022 May 18:bloodadvances.2021006672. doi: 10.1182/bloodadvances.2021006672. Epub ahead of print. PMID: 35584396.