Safety and Efficacy of Gene Therapy of the Sickle Cell Disease by Transplantation of an Autologous CD34+ Enriched Cell Fraction That Contains CD34+ Cells Transduced ex Vivo With the GLOBE1 Lentiviral Vector Expressing the βAS3 Globin Gene in Patients With Sickle Cell Disease (DREPAGLOBE)

Inclusion Criteria: * \- Age 12-20 years * Diagnosis of HbSS or S-beta zero thalassemia by Hb electrophoresis or genetic analysis. * Clinical history or ongoing evidence of severe sickle cell anemia with one OR more of the following clinical complications demonstrating disease severity: * At least 3 vaso occlusive crises requiring hospitalization, under hydroxyurea or transfusion, within 2 years prior to enrollment * One severe acute chest syndrome (ACS) hospitalized in intensive care unit * At least 2 episodes of ACS within the prior 3 years), including one under HU. * Acute priapism (at least 2 episodes \> 3h in the preceding year or in the year prior to the start of a regular transfusion program), OR stuttering priapism ≥ 1 by week under sickle cell treatment (HU, transfusion or phlebotomy). * Cerebral vasculopathy confirmed by MRA (magnetic resonance angiography) without Moya-moya * Presence of sickle cell cardiomyopathy documented by Doppler echocardiography (left ventricular ejection fraction (LVEF) \<55% AND tricuspid regurgitation velocity \>2.5m/s on cardiac echocardiograph), * Tricuspid regurgitation velocity \>2.8m/s on cardiac echocardiograph without pulmonary hypertension confirmed by right heart catheterization (mPAP\<25mmHg) * Failed hydroxyurea (HU) therapy, were unable to tolerate HU therapy, or, if 18 years of age or older, have actively made the choice to not take the recommended daily HU regimen. Inadequate clinical response to HU, defined …