Neurocognitive Functioning in Adults Who Underwent Nonmyeloablative HLA-Matched Sibling Hematopoietic Stem Cell Transplant (SCT) for Sickle Cell Disease (SCD)

Abstract

Individuals with SCD are at risk for neurocognitive impairments. While potentially curative, SCTs come with their own risk of neurotoxicities, particularly from radiation and high-dose ablative chemotherapies. Newer, nonmyeloablative regimens may prevent some of these toxicities. This study examines the long-term cognitive impact of nonmyeloablative transplants in adults with SCD. Seventeen adults (11 males; mean age = 32.2 years, SD=9.0, range 17–52) participated in neuropsychological evaluations before transplant and 12 months post-transplant, as part of a research protocol at the National Heart Lung and Blood Institute. Donors were HLA-matched siblings; the conditioning regimen consisted of alemtuzumab and 300cGy total body irradiation, and they received sirolimus for graft-versus-host disease prophylaxis. Evaluations assessed global cognition, processing speed, memory, attention, and executive functions. Patients completed the PROMIS Physical Functioning questionnaire. Global cognition was within normal limits. Mean Verbal and Performance IQ scores were average at baseline and follow-up, with no significant changes noted. Mean processing speed scores were average, and increased significantly from baseline (M=92.1, SD=10.1) to 12 months (M=99.2, SD=11.6, t=2.1, p=.013). Mean scores on memory, attention and executive tests were average and stable across time points. No group declines in mean cognitive scores were noted. Mean t-scores on the physical functioning questionnaire increased from 41.6 (SD=4.7) to 49.0 (SD=10.0; t=3.4, p=.01), indicating significant improvement from baseline to 12 months post-transplant. Hemoglobin levels increased significantly from pre-transplant (M=9.1, SD=0.9) to post-transplant (M=13.1, SD=2.2; t=8.9, p<.0001). In this small sample, a comparison of neurocognitive scores from baseline to 12 months post-nonmyeloablative SCT does not indicate any deleterious effects from transplant. In fact, a significant improvement emerged in mental processing speed. Physical functioning also improved per patient questionnaires. As suggested by some prior research, the significant increase in hemoglobin levels may underlie improvements in processing speed.