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Publications

Journal Article Clinical Trial Research Support, Non-U.S. Gov't Ppublish 6 citations

PubMed: 38364110 DOI: 10.1182/blood.2023022011

The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease.

Blood 143(21):2145-2151

Authors: Rowan O Brothers, Katherine B Turrentine, Mariam Akbar, Sydney Triplett, Hongting Zhao, Tara M Urner, Adam Goldman-Yassen, Richard A Jones, Jack Knight-Scott, Sarah S Milla, Shasha Bai, Amy Tang, R Clark Brown, Erin M Buckley

Affiliations

  • Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA.
  • Department of Radiology and Imaging Sciences, Children's Healthcare of Atlanta and Emory University, Atlanta, GA.
  • Department of Radiology, Children's Healthcare of Atlanta, Atlanta, GA.
  • Department of Pediatric Radiology, Children's Hospital Colorado, Aurora, CO.
  • Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO.
  • Pediatric Biostatistics Core, Emory University School of Medicine, Atlanta, GA.
  • Department of Pediatrics, Children's Healthcare of Atlanta and Emory University, Atlanta, GA.
  • Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA.
  • Department of Pediatrics, Emory University, Atlanta, GA.
  • Children's Research Scholar, Children's Healthcare of Atlanta, Atlanta, GA.

Abstract

Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin-labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI-measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.

MeSH

Cells, Hemoglobins, Hematology, Anemia, Sickle Cell, Blood Circulation, Hemodynamics, Child

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