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Myeloablative allogeneic hematopoietic cell transplantation associated with significant cognitive decline
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Patients who received myeloablative allogeneic hematopoietic stem cell transplantation experienced significant declines in cognitive function, whereas those who received a less intensive therapy appeared to experience a delayed decline, study data showed.
“Impaired cognition is an increasingly recognized consequence of myeloablative allogeneic hematopoietic cell transplantation and could affect societal reintegration and return to work or school,” Smita Bhatia, MD, MPH, of the School of Medicine at the University of Alabama, Birmingham, and colleagues wrote.
The researchers wrote that although previous studies have addressed the effects of HSCT, they were limited by study design, sample size, a dearth of autologous HSCT recipients, or lack of a healthy comparison group.
“These limitations likely have contributed to mixed evidence with respect to the extent and nature of cognitive compromise in [HSCT] survivors,” Bhatia and colleagues wrote. “In addition, the increasing use of reduced-intensity conditioning demands an understanding of the trajectory of cognitive functioning in this growing population.”
The researchers performed a prospective longitudinal study of 477 patients (median age, 52 years) who received HSCT (n = 236 autologous HSCT recipients, 128 reduced-intensity allogeneic HSCT recipients, 113 myeloablative HSCT recipients). All patients, as well as 99 matched healthy controls (median age, 55 years), underwent testing at 6 months, followed by 1, 2 and 3 years. Global deficit scores and practice effect-adjusted domain-specific T scores served as the main outcomes.
Bhatia and colleagues used piecewise generalized estimating equation models to compare groups and identify associated variables, as well as trends after therapy.
Controls and patients who received autologous or reduced-intensity HSCT had comparable cognitive scores.
Compared with controls, patients who underwent myeloablative HSCT demonstrated significantly lower scores for executive function, auditory memory, verbal speed, processing speed and fine motor dexterity after HSCT (P < .001).
Among patients who received reduced-intensity HSCT, scores did not change from before therapy to 6 months after therapy, although fine motor dexterity scores fell significantly after myeloablative HSCT (P < .001).
At 3 years after HSCT, patients who received less intensive treatment showed significant declines in verbal fluency, working memory and executive function (P < .003).
Factors associated with cognitive decline following HSCT included older age, male sex, lower income, lower education and lower cognitive reserve.
Global cognitive impairment occurred in 18.7% of autologous HSCT recipients, and 35.7% of patients who received allogeneic HSCT. Patients who underwent allogeneic HSCT and experienced global cognitive deficit had a 9.9-fold increased risk for not returning to work by 3 years after therapy. No association occurred between global cognitive deficit and failure to return to work among those who received autologous HSCT, according to a multivariable analysis.
“Cognitive functioning needs to be monitored after HSCT among patients identified to be at the highest risk to facilitate targeted cognitive interventions, such as cognitive training,” the researchers wrote. – by Andy Polhamus
Disclosures: One author reports patents, royalties or other intellectual property with Mustang Bio. No other authors report any relevant financial disclosures.
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