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)
Sylvie Chevret
(1, 2)
,
Suzanne Verlhac
(3, 4, 2)
,
Elisabeth Ducros-Miralles
(3, 5)
,
Jean-Hugues Dalle
(4, 2)
,
Regis Peffault de Latour
(1, 2)
,
Mariane de Montalembert
(6, 7)
,
Malika Benkerrou
(4, 7)
,
Corinne Pondarré
(8, 3, 5)
,
Isabelle Thuret
(9, 10)
,
Corinne Guitton
(11, 12)
,
Emmanuelle Lesprit
(13, 2)
,
Maryse Etienne-Julan
(14, 15)
,
Gisèle Elana
(16, 14)
,
Jean-Pierre Vannier
(17, 18)
,
Patrick Lutz
(19, 20)
,
Bénédicte Neven
(6, 7)
,
Claire Galambrun
(9, 10)
,
Catherine Paillard
(19, 20)
,
Camille Runel
(21, 22)
,
Charlotte Jubert
(21, 22)
,
Cécile Arnaud
(3, 5)
,
Annie Kamdem
(3, 5)
,
Valentine Brousse
(6, 7)
,
Florence Missud
(4, 2)
,
Marie Petras
(14, 15)
,
Lydia Doumdo-Divialle
(14, 15)
,
Claire Berger
(23, 24)
,
Françoise Fréard
(3, 5)
,
Olivier Taieb
(25, 26)
,
Elise Drain
(25, 26)
,
Monique Elmaleh
(4, 2)
,
Manuela Vasile
(4, 2)
,
Yacine Khelif
(27)
,
Myriam Bernaudin
(27)
,
Philippe Chadebech
(28, 5, 29)
,
France Pirenne
(28, 5, 29)
,
Gérard Socié
(1, 2)
,
Françoise Bernaudin
(3, 5)
1
AP-HP -
Hopital Saint-Louis [AP-HP]
2 UPD7 - Université Paris Diderot - Paris 7
3 CHIC - Centre Hospitalier Intercommunal de Créteil
4 Hôpital Robert Debré
5 UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12
6 Hôpital Necker - Enfants Malades [AP-HP]
7 UPD5 - Université Paris Descartes - Paris 5
8 Centre Léon Bérard [Lyon]
9 TIMONE - Hôpital de la Timone [CHU - APHM]
10 AMU - Aix Marseille Université
11 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
12 UP11 - Université Paris-Sud - Paris 11
13 CHU Trousseau [APHP]
14 UA - Université des Antilles
15 CHU Pointe-à-Pitre/Abymes [Guadeloupe]
16 CHU de la Martinique [Fort de France]
17 Hôpital Charles Nicolle [Rouen]
18 UNIROUEN - Université de Rouen Normandie
19 Hôpital de Hautepierre [Strasbourg]
20 UNISTRA - Université de Strasbourg
21 CHU Bordeaux
22 UB - Université de Bordeaux
23 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
24 UJM - Université Jean Monnet - Saint-Étienne
25 Hôpital Avicenne [AP-HP]
26 UP13 - Université Paris 13
27 UNICAEN - Université de Caen Normandie
28 Etablissement Français du Sang [Île-de-France Mondor]
29 U955 Inserm - UPEC - IMRB - "Transfusion et Maladies du Globule Rouge" [Créteil]
2 UPD7 - Université Paris Diderot - Paris 7
3 CHIC - Centre Hospitalier Intercommunal de Créteil
4 Hôpital Robert Debré
5 UPEC UP12 - Université Paris-Est Créteil Val-de-Marne - Paris 12
6 Hôpital Necker - Enfants Malades [AP-HP]
7 UPD5 - Université Paris Descartes - Paris 5
8 Centre Léon Bérard [Lyon]
9 TIMONE - Hôpital de la Timone [CHU - APHM]
10 AMU - Aix Marseille Université
11 Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
12 UP11 - Université Paris-Sud - Paris 11
13 CHU Trousseau [APHP]
14 UA - Université des Antilles
15 CHU Pointe-à-Pitre/Abymes [Guadeloupe]
16 CHU de la Martinique [Fort de France]
17 Hôpital Charles Nicolle [Rouen]
18 UNIROUEN - Université de Rouen Normandie
19 Hôpital de Hautepierre [Strasbourg]
20 UNISTRA - Université de Strasbourg
21 CHU Bordeaux
22 UB - Université de Bordeaux
23 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
24 UJM - Université Jean Monnet - Saint-Étienne
25 Hôpital Avicenne [AP-HP]
26 UP13 - Université Paris 13
27 UNICAEN - Université de Caen Normandie
28 Etablissement Français du Sang [Île-de-France Mondor]
29 U955 Inserm - UPEC - IMRB - "Transfusion et Maladies du Globule Rouge" [Créteil]
Jean-Hugues Dalle
- Fonction : Auteur
- PersonId : 767006
- ORCID : 0000-0002-8406-0793
Claire Berger
- Fonction : Auteur
- PersonId : 757697
- ORCID : 0000-0001-9875-5150
Gérard Socié
- Fonction : Auteur
- PersonId : 758626
- ORCID : 0000-0002-2114-7533
- IdRef : 061658243
Résumé
Background: 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.
Design: 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.
Objectives: To show that genoidentical transplantation decreases velocities significantly more than chronic transfusion in SCA children at risk of stroke.
Discussion: 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.
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