Purpose Research has documented cognitive deficits both before and after high-dose treatment followed by allogeneic hematopoietic cell transplantation (HCT), with partial recovery by 1 year. This study prospectively examined the trajectory and extent of long-term cognitive dysfunction, with a focus on 1 to 5 years after treatment.

Patients and Methods Allogeneic HCT recipients completed standardized neuropsychological tests including information processing speed (Trail Making A and Digit Symbol Substitution Test), verbal memory (Hopkins Verbal Learning Test–Revised), executive function (Controlled Oral Word Association Test and Trail Making B), and motor dexterity and speed (Grooved Pegboard). Survivors (n = 92) were retested after 80 days and 1 and 5 years after transplantation. Case-matched controls (n = 66) received testing at the 5-year time point. A Global Deficit Score (GDS) summarized overall impairment. Response profiles were analyzed using linear mixed effects models.

Results Survivors recovered significant cognitive function from post-transplantation (80 days) to 5 years in all tests (P < .0001) except verbal recall (P > .06). Between 1 and 5 years, verbal fluency improved (P = .0002), as did executive function (P < .01), but motor dexterity did not (P > .15), remaining below controls (P < .0001) and more than 0.5 standard deviation below population norms. In GDS, 41.5% of survivors and 19.7% of controls had mild or greater deficits (NcNemar test = 7.04, P = .007).

Conclusion Although neurocognitive function improved from 1 to 5 years after HCT, deficits remained for more than 40% of survivors. Risk factors, mechanisms and rehabilitation strategies need to be identified for these residual deficits.