Long-term Comparative Cerebrovascular Outcome After Transplantation vs Standard Care in Sickle Cell Anemia (DREPAGREFFE2)

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

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Stenosis; Cerebral Ischemia
• Intervention / Treatment: Other: blood collection

Detailed Description

The present observational study has the objective to reevaluate at distance the cohort of 67 children with sickle cell anemia enrolled in the "Drepagreffe"trial 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

• Study Type: Observational
• Enrollment (Actual): 67

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33000
    • Groupe hospitalier Pellegrin
  • Créteil, France, 94000
    • Centre Hospitalier Intercommunal de Créteil
  • Créteil, France, 94000
    • Hôpital Henri Monr - APHP
  • La Guadeloupe, France, 97110
    • CHU de la Guadeloupe
  • Le Kremlin-Bicêtre, France, 94270
    • Hôpital Bicêtre AP-HP
  • Lyon, France, 69008
    • IHOPe
  • Lyon, France, 69737
    • CHU de Lyon
  • Marseille, France, 13005
    • Hôpital de la Timone
  • Montpellier, France, 34295
    • CHU de Montpellier
  • Paris, France, 75015
    • Hôpital Necker - AP-HP
  • Pau, France, 64000
    • CH de Pau
  • Rennes, France, 35033
    • CHU de Rennes
  • Strasbourg, France, 67200
    • Hôpital Hautepierre
  • IDF
    • Paris, IDF, France, 75019
      • Hôpital Robert Debré AP-HP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Population concerned 67 patients included in 2011-2013 in the DREPAGREFFE protocol [NCT 01340404]

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients included in Drepagreffe 1 study (NCT01340404); biological collection	Other: blood collection; blood collection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Intercommunal Creteil
• Collaborators: Etablissement Français du Sang; Centre National de la Recherche Scientifique, France

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2022
• Primary Completion (Actual): January 5, 2025
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: September 13, 2021
• First Posted (Actual): September 23, 2021

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: transplantation
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Constriction, Pathologic; Anemia, Sickle Cell; Brain Ischemia; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: DREPAGREFFE2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No