Allogeneic HSCT and Cognitive Impairment

New Orleans—Compared with a healthy group, patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) had worse cognitive impairment on measures such as executive function, processing speed, verbal fluency, and fine motor dexterity, according to a 2-year, prospective, longitudinal study.

In addition, patients receiving full intensity conditioning are at risk of poor cognitive functioning, while patients undergoing reduced intensity conditioning are typically spared. For patients undergoing HSCT, patients who were male, of Hispanic ethnicity, low education, low income, and high fatigue were at a higher risk of poorer cognitive function.

The authors of the study also found that there was no association between telomere length and cognitive impairment among male HSCT recipients, but telomere shortening before HSCT was associated with poorer cognitive functioning after HSCT in females.

Smita Bhatia, one of the study’s authors, presented the results during a media briefing at the ASH meeting. The Leukemia & Lymphoma Society, a nonprofit organization that funds blood cancer research, supported this study.

Dr. Bhatia noted that impaired cognition is common after transplantation. She was involved in a study that found impaired cognition was partially responsible for patients not returning to work following transplantation. Still, she said that before this study, researchers had not examined cognitive function after reduced intensity transplantation and had not compared healthy control groups in a “rigorous fashion.”

“We are barely scratching the surface of trying to understand the pathogenesis or what actually happens when patients develop cognitive impairment after transplantation,” Dr. Bhatia said.

This study included patients with full and reduced intensity HSCT as well as a healthy control comparison group. The authors hypothesized that shorter telomere lengths may play a role in post-HSCT cognitive impairment. Dr. Bhatia defined telomeres as repetitive DNA-protein structures that cap the ends of the chromosomes and protect the chromosomes’ integrity.

As people age, telomeres become shorter with each cell division, according to Dr. Bhatia. She added that chemotherapy and radiation “really hastens” the shortening, while glial cells in the brain are mitotic and divide and are susceptible to telomere shortening. In addition, telomere shortening from blood samples correlates with severity of Alzheimer’s disease.

Dr. Bhatia and her coauthors assessed patients before they underwent HSCT as well as at 6 months, 1 year, and 2 years. They then recruited an age- and sex-matched healthy control group and assessed them at the same time periods. They used a 2-hour battery of 14 standardized neurocognitive tests that assessed 8 domains and used healthy control scores to correct for scores from patients undergoing HSCT for practice effects.

The authors also drew blood to obtain DNA before transplantation and used a qPCR-based telomere assay to assess the relative telomere lengths. They used the median telomere length to divide patients into short and long telomere lengths.

There were 242 patients in the HSCT group and 98 healthy controls. Of the patients, 125 undergoing HSCT and 45 in the healthy group were available for assessment at 2 years. Dr. Bhatia said there were a large number of deaths within the 2 years, and many patients were sick and could not participate in the assessment. Of the patients who could participate at 2 years, 80% did so.

The median age of patients undergoing transplantation was 49 years, 62% were males, and 69% had acute leukemia. Furthermore, 48% of patients underwent full intensity HSCT and 52% had reduced intensity HSCT. In the healthy group, the median age was 51 years, and 54% of patients were males.