{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:02:47Z","timestamp":1788627767040,"version":"build-2803163510"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Due to the risk of cerebral vascular injury, children and adolescents with high-risk sickle cell disease (SCD) experience neurocognitive decline over time. Haploidentical stem cell transplantation (HISCT) from human leukocyte antigen-matched sibling donors may slow or stop progression of neurocognitive changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The study is to determine if HISCT can ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression, determine which specific areas of neurocognitive functioning are particularly vulnerable to SCD, and determine if there are age-related differences in neurocognitive functioning over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed neurocognitive and neuroimaging in SCD recipients following HISCT. Children and adolescents with high-risk SCD who received parental HISCT utilizing CD34<jats:sup>+<\/jats:sup> enrichment and mononuclear cell (T-cell) addback following myeloimmunoablative conditioning received cognitive evaluations and neuroimaging at three time points: pre-transplant, 1 and 2\u2009years post-transplant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nineteen participants (13.1\u2009\u00b1\u20091.2\u2009years [3.3\u201320.0]) received HISCT. At 2\u2009years post-transplant, neuroimaging and cognitive function were stable. Regarding age-related differences pre-transplantation, older children (\u226513\u2009years) had already experienced significant decreases in language functioning (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.023), verbal intelligence quotient (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.05), non-verbal intelligence quotient (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.006), and processing speed (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.05), but normalized post-HISCT in all categories.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Thus, HISCT has the potential to ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression. Further studies are required to determine if neurocognitive performance remains stable beyond 2\u2009years post-HISCT.<\/jats:p><jats:p><jats:bold>Clinical trial registration:<\/jats:bold> The study was conducted under an investigator IND (14359) (MSC) and registered at <jats:ext-link>clinicaltrials.gov<\/jats:ext-link> (NCT01461837).<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1263373","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T13:47:47Z","timestamp":1716385667000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Neurocognitive outcome in children with sickle cell disease after myeloimmunoablative conditioning and haploidentical hematopoietic stem cell transplantation: a non-randomized clinical trial"],"prefix":"10.3389","volume":"15","author":[{"given":"Suzanne","family":"Braniecki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott","family":"Vichinsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Walters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Shenoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore B.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie-An","family":"Talano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K.","family":"Parsons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyson","family":"Flower","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Panarella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Fabricatore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshini","family":"Mahanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Milner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"McKinstry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine N.","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmella","family":"van de Ven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell S.","family":"Cairo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/S0140-6736(12)61229-X","article-title":"Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates","volume":"381","author":"Piel","year":"2013","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"4331","DOI":"10.1182\/blood-2010-01-251348","article-title":"The inherited diseases of hemoglobin are an emerging global health burden","volume":"115","author":"Weatherall","year":"2010","journal-title":"Blood"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1177\/003335491312800206","article-title":"Mortality rates and age at death from sickle cell disease: U.S., 1979-2005","volume":"128","author":"Lanzkron","year":"2013","journal-title":"Public Health Rep"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1056\/NEJMra1510865","article-title":"Sickle cell disease","volume":"376","author":"Piel","year":"2017","journal-title":"N Engl J Med"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1056\/NEJM199406093302303","article-title":"Mortality in sickle cell disease. 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