Standard of Care Comparative Arm of Phase 1/2 Gene Therapy Trial DREPAMIR" in Severe Sickle Cell Disease Patients

Inclusion Criteria: * Age 12 - 35 years * Diagnosis of HbSS by Hb electrophoresis and genetic analysis to analyse the alpha locus * 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 the intensive care unit At least 2 episodes of ACS, 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). 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 inadequate clinical response to HU, defined as any one of the following outcomes, while on HU for at least 3 months: 2 or more acute sickle pain crisis requiring hospitalization, requirement of transfusion to maintain Hb \>6.0g/dL, an episode of ACS despite adequate supportive care measures * Karnovsky/Lansky performance score ≥ 60% * Sexually active patients must be willing to use an acceptable method of double-barrier contraception for at least 12 months post-infusion (beyond 12 mont…