Long-term Comparative Cerebrovascular Outcome After Transplantation vs Standard Care in Sickle Cell Anemia

Study Overview
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Brief Summary
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The purpose of the present observational study is to remotely reevaluate the cohort of 67 sickle cell patients with transcranial Doppler-detected cerebral vasculopathy included in the national Sickle Cell Transplant protocol and whose 1- and 3-year results were published in JAMA (Journal of the American Medical Association) in 2019 and in BHJ in 2020.

Detailed Description
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The present observational study has the objective to reevaluate at distance the cohort of 67 children with sickle cell anemia enrolled in the Drepagreffetrial because of cerebral vasculopathy detected by transcranial Doppler. Results at 1 and 3 years were reported in JAMA in 2019 in BHJ in 2020. This trial was the first worldwide prospective study comparing transplantation to standard care in sickle cell disease. Velocities were highly significantly more reduced with a higher proportion of patients with normalized velocities and better quality of life after transplantation than on standard care. Despite a trend to a better ischemic lesions outcome at 3 years, the difference was not significant and cognitive performances were not different between both groups. The biologic study only assessed at enrollment and 1-year showed lower levels of Ang-2 and HGF (hepatocyte growth factor) after transplant and a significant and independent association between Doppler normalization probability with low Ang-2 and BDNF (brain-derived neurotrophic factor) levels.The aim of the present study is to reassess at 9-10 years this cohort with grants allowing to reevaluate cognitive functioning and hypoxia/angiogenic factors not realized in the systematic cohort follow-up

Official Title
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Long-term Comparative Cerebrovascular Outcome After Transplantation vs Standard Care in Children With Sickle Cell Anemia ( DREPAGREFFE-2)

Conditions
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Sickle Cell Disease, Cerebral Ischemia, Stenosis

Intervention / Treatment
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* Other: blood collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient of legal age or minor who participated in the DREPAGREFFE research protocol [NCT 01340404] between December 2010 and June 2013, Having read and understood the information letter Exclusion Criteria: Refusal to participate Patient deceased

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients included in Drepagreffe 1 study (NCT01340404)<br>biological collection | Other: blood collection<br>* blood collection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long term evolution (at 9-10 years) of Ischemic lesion on brain magnetic resonance imaging 10-year measurement of ischemic lesion on magnetic resonance imaging | The MRI-scores, ranging from 0 (best outcome) to 10 (worst outcome), are obtained by adding up the ischemic lesion scores from the left and right sides, i.e., 3 for territorial or 2 for border zone (cortical and subcortical), 1 for white matter and 1 for basal ganglia infarcts and 0 if absent on each side. | within 6 months of inclusion | 
| Long term evolution (at 9-10 years) of arterial stenosis on cerebral and cervical magnetic resonance angiography | The MRA stenosis-scores, ranging from 0 (best outcome) to 32 (worst outcome) are defined as the weighted sums over the 8 assessed cerebral arteries, as 0 if no stenosis, 1 if mild stenosis (25-49%), 2 if moderate stenosis (50-74%), 3 if severe stenosis (75-99%), and 4 if occlusion. | within 6 months of inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long term evolution (at 9-10 years) of cognitive performance | Full Scale Intelligence Quotient (40= worst outcome, 160= best outcome) is measured by Wechsler Intelligence Scale for Children -Fourth Edition (WISC-4) for children 7-16 years of age and by WAIS-3 (Weschler Adult Intelligence Scale-3) for patients older than 16 years | within 6 months of inclusion | 
| Long term evolution (at 9-10 years) of quality of life | Quality of life assessment is collected using the French version of the Pediatric Quality of Life Inventory Generic Core Scale (PedsQLTM 4.0 generic core scales) (physical, emotional, social, school items) (0= worst outcome, 100= best outcome) via self-report and parent proxy-report | within 6 months of inclusion | 
| Evolution at 9-10 years of factors of hypoxia and oxidative stress | Assessment on plasma Phosphatidyl-serine expression VEGF, Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2),EPO, HIF-1, BDNF, PDGF-AA | within 6 months of inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transplantation