Neurocognitive Function Stabilizes after Hematopoietic Cell Transplant in Children with Sickle Cell Disease with Underlying Cerebrovascular Issues

Introduction Cerebrovascular involvement in sickle cell disease (SCD) often results in neurocognitive functional deficits and can result in a long-term impact. Hematopoietic cell transplant (HCT) is indicated as a curative therapy in children with history of stroke while on chronic transfusions. Neurocognitive outcome following an allogeneic HCT in pediatric patients with SCD is notably scarce. In the era of burgeoning novel therapies, there is a critical need for quantitation of functioning in patients with SCD to demonstrate therapeutic as well as functional efficacy. Objective To report pre- and post-HCT neurocognitive outcomes in children with SCD identified with cerebrovascular issues. Methods We retrospectively reviewed pre and post HCT neurocognitive outcomes of pediatric patients with SCD who underwent HCT at University of Minnesota in the past 5 years and had underlying concerns with cerebrovascular disease. As a part of comprehensive evaluation, these patients underwent evaluations by pediatric neuropsychologists pre HCT as well as annually thereafter. Patients were tested in three main domains: 1) Intelligent quotient (IQ), measured using the Wechsler Intelligence Scale for Children or Kaufman Assessment Battery for Children, 2) adaptive functioning, measured using the Behavior Assessment System for Children, Parent Form and 3) visual-motor integration, measured using the Beery-Buktenica Developmental Test of Visual Motor Integration. Results Five patients were identified who met the above criteria. Three patients had either an elevated or conditional transcranial doppler with raised velocities while 2 patients were identified with silent stroke and were receiving chronic transfusions. Two patients received a matched sibling HCT, one received a matched unrelated HCT using busulfan and fludarabine based conditioning. Two patients underwent a haploidentical HCT and received total body irradiation in the conditioning. Prior to HCT, though majority of patients obtained below average (n=3) to an average IQ score (n=1), one patient had an impaired IQ score (Standard Score = 60). IQ scores were stable and not significantly changed for patients post-HCT. However, the IQ score declined for 1 patient at a year post-HCT, from the below average range to impaired range. Pre-HCT parent-reported adaptive functioning skills measured within the age-typical (average) range for 3 of the 4 patients that completed this measure. For all patients, adaptive scores were stable post HCT. Parent ratings of adaptive skills were broadly consistent with IQ scores obtained from direct testing. Conclusion Neurocognitive function remains overall stable post-HCT in children with SCD who undergo transplant for underlying cerebrovascular issues. Larger cohorts with long term follow up is required to further determine the stability of neurocognitive in these patients.