Neurocognitive Outcome in Children with Sickle Cell Disease After Myeloimmunoablative Conditioning and Haploidentical Hematopoietic Stem Cell Transplantation: a Non-randomized Clinical Trial

Overview

Journal Front Neurol

Specialty Neurology

Date 2024 Jun 6

PMID 38841694

Authors

Suzanne Braniecki

Elliott Vichinsky

Mark C Walters

Shalini Shenoy

Qiuhu Shi

Theodore B Moore

Julie-An Talano

Susan K Parsons

Allyson Flower

Anne Panarella

Sandra Fabricatore

Erin Morris

Harshini Mahanti

Jordan Milner

Robert C McKinstry

Christine N Duncan

Carmella van de Ven

Mitchell S Cairo

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Objectives: 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.

Methods: We performed neurocognitive and neuroimaging in SCD recipients following HISCT. Children and adolescents with high-risk SCD who received parental HISCT utilizing CD34 enrichment and mononuclear cell (T-cell) addback following myeloimmunoablative conditioning received cognitive evaluations and neuroimaging at three time points: pre-transplant, 1 and 2 years post-transplant.

Results: Nineteen participants (13.1 ± 1.2 years [3.3-20.0]) received HISCT. At 2 years post-transplant, neuroimaging and cognitive function were stable. Regarding age-related differences pre-transplantation, older children (≥13 years) had already experienced significant decreases in language functioning ( < 0.023), verbal intelligence quotient ( < 0.05), non-verbal intelligence quotient ( < 0.006), and processing speed ( < 0.05), but normalized post-HISCT in all categories.

Conclusion: 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 years post-HISCT. The study was conducted under an investigator IND (14359) (MSC) and registered at clinicaltrials.gov (NCT01461837).

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