Functional and Radiologic Assessment of the Brain after Reduced-Intensity Unrelated Donor Transplantation for Severe Sickle Cell Disease: Blood and Marrow Transplant Clinical Trials Network Study 0601

Biol Blood Marrow Transplant. 2019 May;25(5):e174-e178. doi: 10.1016/j.bbmt.2019.01.008. Epub 2019 Jan 11.

Abstract

Stroke and cognitive decline are hallmarks of sickle cell disease (SCD). The natural history of SCD predicts progressive loss of 1 IQ point per year attributable to disease-related pathology. Hematopoietic cell transplantation (HCT) is curative by reverting to donor-derived erythropoiesis, but evidence that HCT can positively influence disease-induced cognitive decline is lacking. The Sickle Cell Unrelated Transplant Trial prospectively evaluated cognition and brain magnetic resonance imaging (MRI) findings at 2 years after reduced-intensity conditioning followed by unrelated donor HCT. Thirteen study participants completed pre-HCT and post-HCT assessments of intelligence. The mean age of participants was 12.5 ± 3.3 years (range, 6.7 to 17.4 years). Eleven of the 13 recipients completed imaging studies at baseline and post-HCT. Seven had overt stroke pre-HCT, and 1 had an elevated transcranial Doppler velocity with abnormal MRI. The mean Full-Scale IQ was stable: 90.9 ± 13 at baseline and 91.2 ± 13 post-HCT. The mean Performance IQ was 89.9 ± 13 at baseline versus 90.9 ± 13 post-HCT, and mean Verbal IQ was 93.4 ± 13 at baseline versus 93.2 ± 13 post-HCT, respectively. Six recipients had stable MRI; 2 showed resolution of all areas of infarction. Three had additional infarcts post-HCT noted at the 2-year time point. This is the first report describing stabilization of IQ and central nervous system outcomes after unrelated donor HCT despite previous central nervous system morbidity and post-HCT posterior reversible encephalopathy syndrome. These preliminary results post-HCT suggest that HCT may stabilize the cognitive decline of SCD and should continue to be followed over the long term.

Keywords: Brain MRI; Neurocognition; Sickle cell disease; Stem cell transplantation.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / therapy*
  • Brain / diagnostic imaging*
  • Brain / pathology
  • Central Nervous System Diseases / etiology
  • Child
  • Cognition*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Infarction / diagnostic imaging
  • Intelligence Tests
  • Magnetic Resonance Imaging
  • Transplantation Conditioning / methods
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors