Design of the DREPAGREFFE trial: A prospective controlled multicenter study evaluating the benefit of genoidentical hematopoietic stem cell transplantation over chronic transfusion in sickle cell anemia children detected to be at risk of stroke by transcranial Doppler (NCT 01340404)

Children with sickle cell anemia (SCA) have an 11% risk of stroke by the age of 18. Chronic transfusion applied in patients detected to be at risk by transcranial Doppler allows a significant reduction of stroke risk. However, chronic transfusion exposes to several adverse events, including alloimmu...

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Bibliographic Details
Published in:Contemporary clinical trials 2017-11, Vol.62, p.91-104
Main Authors: Chevret, Sylvie, Verlhac, Suzanne, Ducros-Miralles, Elisabeth, Dalle, Jean-Hugues, de Latour, Regis Peffault, de Montalembert, Mariane, Benkerrou, Malika, Pondarré, Corinne, Thuret, Isabelle, Guitton, Corinne, Lesprit, Emmanuelle, Etienne-Julan, Maryse, Elana, Gisèle, Vannier, Jean-Pierre, Lutz, Patrick, Neven, Bénédicte, Galambrun, Claire, Paillard, Catherine, Runel, Camille, Jubert, Charlotte, Arnaud, Cécile, Kamdem, Annie, Brousse, Valentine, Missud, Florence, Petras, Marie, Doumdo-Divialle, Lydia, Berger, Claire, Fréard, Françoise, Taieb, Olivier, Drain, Elise, Elmaleh, Monique, Vasile, Manuela, Khelif, Yacine, Bernaudin, Myriam, Chadebech, Philippe, Pirenne, France, Socié, Gérard, Bernaudin, Françoise
Format: Article
Language:English
Subjects:
Adolescent
Anemia, Sickle Cell - complications
Anemia, Sickle Cell - therapy
Blood Transfusion - economics
Blood Transfusion - methods
Cerebral vasculopathy
Child
Child, Preschool
Chronic transfusion
Cognition
Cognitive science
Female
Genetic randomization
Hematopoietic stem cell transplantation
Hematopoietic Stem Cell Transplantation - adverse effects
Hematopoietic Stem Cell Transplantation - economics
Hematopoietic Stem Cell Transplantation - methods
Humans
Iron Overload - etiology
Male
Neuroscience
Prospective Studies
Quality of Life
Research Design
Sickle cell anemia
Stroke - diagnostic imaging
Stroke - etiology
Transcranial Doppler
Transfusion Reaction
Ultrasonography, Doppler, Transcranial
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Summary:Children with sickle cell anemia (SCA) have an 11% risk of stroke by the age of 18. Chronic transfusion applied in patients detected to be at risk by transcranial Doppler allows a significant reduction of stroke risk. However, chronic transfusion exposes to several adverse events, including alloimmunization and iron overload, and is not curative. Hematopoietic stem cell transplantation allows termination of the transfusion program, but its benefit has not been demonstrated. DREPAGREFFE (NCT01340404) is a multicenter, prospective trial enrolling SCA children younger than 15years receiving chronic transfusion due to a history of abnormal transcranial Doppler (velocities ≥200cm/s). Only those with at least one non-SCA sibling and parents accepting HLA-typing and transplantation with a genoidentical donor were eligible. Chronic transfusion was pursued in patients with no available donor, whereas others were transplanted. Comparison between the 2 arms (transfusion vs transplantation) was analyzed using both genetic randomization and propensity-score matching as a sensitivity analysis. The primary end-point was the velocity measure at 1year. Secondary endpoints were the incidence of stroke, silent cerebral infarcts and stenoses, cognitive performance in comparison with siblings, allo-immunization, iron-overload, phosphatidyl-serine, angiogenesis/hypoxia, brain injury-related factor expression, quality of life and cost. To show that genoidentical transplantation decreases velocities significantly more than chronic transfusion in SCA children at risk of stroke. DREPAGREFFE is the first prospective study to evaluate transplantation in SCA children. It compares the outcome of cerebral vasculopathy following genoidentical transplantation versus chronic transfusion using genetic randomization and causal inference methods.
ISSN:1551-7144
1559-2030
DOI:10.1016/j.cct.2017.08.008