Brief Summary: \* A short description of the clinical study, including a brief statement of the clinical study's hypothesis, written in language intended for the lay public. Limit: 5000 characters. Severe forms of sickle cell syndrome are characterized by the occurrence of repeated vaso-occlusive crises (CVO), early complications and a high morbidity and mortality in these patients. Intensified management is then required, with the introduction of hydroxyurea treatment and then, if it proves ineffective, a transfusion program or even a haematopoietic stem cell allograft. These latter treatments present significant risks of adverse effects for the patient (haemochromatosis, erythrocyte alloimmunisation for the transfusion program, risk of GVH, chemotherapy-related toxicity, MVO for the allograft). Hydroxyurea (HU) is the first treatment based on the specific pathophysiology of sickle cell disease. It is the first line of therapeutic intensification for adult patients and children (age ≥ 2 years) with major sickle cell disease. By mainly increasing the percentage of fetal haemoglobin (HbF), HU decreases the frequency of CVO, complications, hospitalizations and prolongs the life expectancy of patients. The initial dose of HU, recommended by the ANSM, is 15 mg/kg/d once daily. However, the optimal dose cannot be predicted at the start of treatment, which is why a dosage adjustment is essential. The usual dose is between 15 and 35 mg/kg per day. Typically, the dose is increased every 3 months until a mild myelosuppression tolerated by the patient is reached, indicating that the maximum tolerated dose (MTD) has been reached. When the dose of HU has reached the MTD, the ratio of clinical (reduced frequency of vaso-occlusive attacks) and biological (better % of HbF) benefits to risk (toxicity) is optimal for the patient. The disadvantages of this practice are that: * dose escalation can be long (9-12 months) * clinicians may be reluctant to escalate HU to MTD * patients are treated sub-optimally during the therapeutic adaptation period. Recent work has shown that it is beneficial for the patient to adjust the initial dose using a pharmacological therapeutic approach in addition to monitoring haematological tolerance. Thus, by customizing the dose of HU using an area under the curve (AUC) measurement at the initial intake of HU at a standardized dose (20 mg/kg/day), the MTD would be achieved in a faster time frame of 6-9 months. The primary objective of our trial is to identify the methodology that will most effectively decrease the time to reach the MTD (therapeutic target). The immediate benefit will be a reduction in CVO which is the major clinical problem and leads to a risk of complications in sickle cell disease.