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Reduced-intensity HSCT recipients spared from post-HSCT cognitive impairment
NEW ORLEANS — Patients who receive full-intensity hematopoietic stem cell transplantation are at risk for cognitive impairment, but reduced-intensity transplantation mitigated the risk, according to study results presented at the ASH Annual Meeting and Exposition.
Also, telomeric shortening prior to HSCT was associated with poorer cognitive function among women, results showed.
Smita Bhatia
Alysia Bosworth, CCRP, and Smita Bhatia, MD, MPH, of the department of population sciences at City of Hope in Duarte, Calif., and colleagues evaluated data from 242 patients (median age, 49 years; range, 19-71). Most patients (69%) had a primary diagnosis of acute leukemia, 14% had lymphoma and 17% had another hematologic malignancy.
Bosworth and colleagues used 14 neuropsychological tests to assess patients’ cognitive function prior to HSCT. The tests evaluated executive function; processing and verbal speed; verbal fluency; working, auditory and visual memory; and fine motor dexterity.
The researchers assessed patients again 6 months (n=165), 1 year (n=155) and 2 years (n=125) post-HSCT. Results were compared with those of 98 healthy controls (median age, 51 years) matched for age and sex.
Fifty-two percent of the study population received reduced-intensity HSCT. Of those who received full-intensity HSCT, 72% underwent myeloablative total body irradiation.
Researchers observed chronic graft-versus-host disease in 51% of HSCT recipients.
Overall, patients who underwent HSCT demonstrated reduced executive function (P=.0008), processing speed (P=.003), verbal fluency (P=.003) and motor dexterity (P=.001) compared with controls.
Multivariable analysis identified several significant contributors to cognitive impairment after HSCT, including male sex, older age, Hispanic ethnicity and high levels of fatigue. Low levels of education, income and cognitive reserve also contributed to cognitive impairment.
After adjustments for those variables, Bosworth and colleagues determined patients who underwent high-intensity HSCT were at increased risk for impaired executive functioning (P=.01), processing speed (P=.0005), verbal speed (P=.0002) and visual memory (P=.002) compared with those who underwent reduced-intensity HSCT.
The researchers reported no significant difference in cognitive function between patients who underwent reduced-intensity HSCT and healthy controls (P˃.1).
In a longitudinal, multivariable analysis, researchers evaluated patients for telomeric shortening. Shorter telomeres — repetitive DNA protein structures that are localized to the ends of chromosomes and that protect chromosome integrity — are thought to play a role in cognitive impairment after HSCT.
Results showed short telomeres pre-HSCT were significantly associated with reduced executive function (P=.004), processing speed (P=.009), verbal speed (P=.009) and working memory (P=.003) among women after HSCT.
“As our results isolate a specific group of patients who would be considered high risk for cognitive impairment, including those who receive full-intensity transplants, it will be important for clinicians to evaluate and offer services to help these patients regain that function after transplant,” Bosworth said.
Efforts to identify potential strategies are under way, Bhatia said.
“There are trials being conducted looking at behavioral therapy and at pharmacological therapy in terms of ADHD-like drugs that can be used to improve processing speed, attention and memory for these patients,” Bhatia said during a press conference. “But it’s primarily behavioral therapy. So for people who are currently in college or educational settings, a special disposition and services for them should exist to help them improve these functions. For people who have jobs that require higher levels of executive function, providing them with behavioral therapy will help them cope with these circumstances.”
For more information:
Bosworth A. Abstract #913. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10; New Orleans.
Disclosure: The researchers report no relevant financial disclosures. The Leukemia & Lymphoma Society funded the study.