Impact of Hydroxyurea on Neurocognitive Function and Quality of Life in Children with Sickle Cell Anemia

Background: Beginning in infancy, children with sickle cell anemia (SCA) experience severe anemia, acute and chronic pain, fatigue, and progressive multi-organ damage including a substantially increased risk of stroke during childhood. Neurocognitive deficits and poor health-related quality of life (HRQL) are also well recognized. Early screening for stroke risk with Transcranial Doppler ultrasound (TCD) and initiation of monthly red blood cell transfusions in children with SCA and abnormal TCD velocities has been proven to substantially decrease the risk of overt stroke; however, chronic transfusion is associated with a heavy patient burden and increased morbidity that can reduce access and make its long-term use untenable. The NIH funded, phase-III, multi-center TCD with Transfusion Changing to Hydroxyurea (TWiTCH) randomized controlled trial established that after a year of monthly blood transfusion, children with abnormal TCD velocities can safely transition to oral hydroxyurea for primary stroke prevention. However, the effect of this transition on neurocognitive and HRQL outcomes was not previously known. This dissertation research utilizing data from the TWiTCH trial provides the first longitudinal comparison of the effects of monthly transfusion and oral hydroxyurea therapy on neurocognitive and HRQL outcomes including fatigue in children with SCA. Results: After a mean 23-months of follow-up, compared to children randomized to continue monthly blood transfusions, the children who transitioned to hydroxyurea did not experience any significant decline in neurocognitive function and in some domains, specifically processing speed and attention, demonstrated significant improvement compared to those who continued transfusions. Additionally, children who transitioned to hydroxyurea reported significantly greater treatment associated quality of life, and improvement in general fatigue scores compared to the children who continued monthly transfusions, with no significant worsening of general or sickle cell disease specific HRQL measures. Discussion: These findings provide additional evidence supporting implementation of clinical guidelines regarding transition from blood transfusion to hydroxyurea for primary stroke prevention, which has the potential to increase access to stroke prevention measures for children with SCA in the U.S. and globally. This analysis also adds to the growing body of evidence supporting hydroxyurea therapy for the prevention of neurocognitive sequelae in children with SCA, and for the use of hydroxyurea to optimize HRQL and reduce fatigue. Increased adoption and utilization of hydroxyurea has the potential to reduce both the individual and public health burden of sickle cell disease.

Author dc:creator

• Nicole Mortier (23292049)

• Children with Sickle Cell Anemia

Statement dc:rights

• In Copyright
• Open Access after 2028-01-01

DOI dc:identifier

https://doi.org/10.25417/uic.31451746.v1

OAI identifier oai:identifier

oai:figshare.com:article/31451746