Sickle cell disease is an inherited hemoglobin disease due to a mutation in the hemoglobin beta gene, resulting in normal hemoglobin A being replaced by abnormal hemoglobin S [1] . In Black Africa, sickle-cell anaemia is the most common haemoglobinopathy and still affects 10 to 40% of the population in some regions of sub-Saharan Africa [2] [3] . In Senegal, the prevalence of hemoglobin S is estimated at 10%, of which 1% is represented by homozygous forms [4] . Drepanocytosis is a serious disease due to its complications (stroke, acute chest syndromes (ACS), vaso-oclusive crises (VCO), etc.).

To reduce these risks of complications, therapeutic strategies have been developed. These are curative therapies such as hematopoietic stem cell transplantation (HSC), and gene therapy; but also palliative therapies such as transfusion therapies, immunotherapy and hydroxyurea. Among all these strategies, hydroxyurea then appears as a therapeutic alternative for certain patients [5] [6] . It is an antimetabolite that has been shown to be effective in some severe forms of sickle cell disease [5] [6] . Hydroxyurea mainly acts on the bone marrow by stimulating the production of fetal Hb which is a powerful inhibitor of polymerization [5] [6] . In our conditions of practice, its prescription was often limited by its low availability in pharmacies, the reluctance of parents and the lack of trained human resources for its use. The opening of an Outpatient Care Unit for Children and Adolescents with Sickle Cell Disease (USAD) in 2017, the training of human resources on sickle cell anemia as well as the action of volunteer donors, have contributed to facilitate the prescription of this molecule, when the indication was presented.

We report our experience in the use of hydroxyurea, in children with homozygous sickle cell disease (SCD) and followed in a specialized hospital.

It was a prospective, longitudinal and descriptive study on a cohort of patients with major sickle cell syndroms during one (1) year (May 2023-April 2024) enrolling 60 patients. This work took place at the Outpatient Care Unit for Sickle Cell Children and Adolescents (USAD), of the Albert Royer National Children’s Hospital Center (CHNEAR) in Dakar, Senegal. We included all patients during our study period, under treatment with hydroxyurea, with up-to-date medical records.

Before the start of hydroxyurea, all patients had a kidney test, a liver test to eliminate children with severe impairment in the function of these two organs. Informed parental consent was required. Were excluded from this study, children whose age was less than 2 years, those whose parents had not given their consent, renal and hepatic insufficiencies as well as those whose follow-up was irregular. The initial dose of hydroxyurea was 10 to 15 mg/kg/day, administered in the form of capsules of 500 mg of Hydrea, distributed over 3 to 7 days per week depending on the child’s weight. The dose gradually increased in case of clinical ineffectiveness, at a rate of 5 mg/kg/day every 3 months, without exceeding 30 to 35 mg/kg/day and without signs of myelotoxicity or side effects. The follow-up was ensured at (M1, M3, M6, M12) by a clinical examination to assess the degree of effectiveness of the drug and its degree of tolerance, a biological assessment including a blood test, a renal and hepatic evaluation. The basal hemoglobin level was calculated based on the average over the year preceding the start of hydroxyurea administration, excluding any episode of acute complications (infection, acute anemia). Medication adherence was calculated by expressing the ratio of the number of days of effective hydroxyurea intake to the total number of prescribed days. All our patients were supplemented daily with folic acid and children under 5 years of age received oral penicillin.

Severe forms of SCD: SCD with/or (kidney damage; priapism; stroke; acute chest syndrom; acute osteonecrosis of femoral head; more than 3 VCO per year; more than 3 hospitaliszations per year; baseline hemoglobin level below 7 g/dl).

Our study involved 60 patients over a period of 12 months.

In our study, 43.33% of children with sickle cell disease on hydroxyurea belonged to the age group 121 to 180 months. This percentage is higher than that reported by Diop et al., where 65.72% of patients were older than 180 months [7] . In contrast, in the study by Mabiala-Babela et al. at CHU Brazzaville, a significant proportion of children under 5 years old were hospitalized for severe complications, with 34.3% of vaso-oclusive crises occurring in these young children [8] . Sex was evenly distributed in our cohort, with 50% boys and 50% girls. This distribution is slightly lower than that observed by Diop et al., who reported a male predominance of 54.28% [7] . Similarly, Boiro et al. found a sex ratio of 1.42 [9] . Dème/Ly reported no gender predominance in his study [10] . This balanced distribution in our study population could be due to the autosomal recessive mode of transmission of sickle cell disease.

The mean basal haemoglobin level in our study was 7.5 g/dl, similar to that reported by Diop et al., who found a mean of 7.3 g/dl [7] . However, in the study by Thiam, the average hemoglobin level was slightly higher than that of our patients (8.6 g/dl) [10] [11] . This situation could be partly explained by the study framework of Thiam et al. which is a natural region with many natural resources (greenery, sea, natural foods). The mean age at start of hydroxyurea treatment in our study was 10 years. An age lower than that observed by Diop et al., who found a mean start-up age of 15 years [7] . On the other hand, Montalembert reported an average starting age comparable to ours, around 9 years [12] . The main indication for the initiation of hydroxyurea in our study was vaso-oclusive crises (VCO), representing 70% of cases, followed by acute chest syndrome (ACS) and severe anemia. These figures are comparable to those reported by Diop et al., who reported VCO as the primary indication in 71.43% of cases, followed by ACS (25.71%) and severe anemia (34.28%) [7] . In the Montalembert study, VCO also represented the majority of indications, although the percentage is slightly lower (65%) [12] . In contrast, a more recent study by Tshilolo et al. had reported a higher proportion of patients treated for ACS (30%), indicating particular attention to this complication in certain regions [13] . After the initiation of hydroxyurea treatment, we observed a significant reduction in pain and length of hospitalization. The mean duration of sickle cell crises in our study was significantly shorter after initiation of hydroxyurea, with a notable reduction in days of hospitalization. Our results are comparable to those observed by De Montalembert, who found that the duration of hospitalizations was significantly reduced in patients on hydroxyurea [12] . Similarly, Diop et al. had reported that the majority of patients on hydroxyurea had hospitalizations of less than 7 days, as was the case with our patients. The positive impact of the treatment was evident, with 80% of patients reporting a significant improvement in their quality of life, reduced pain and hospitalizations, as well as improved haematological parameters. These results were similar to those reported by Diop et al., who had observed a reduction in the number of seizures to 1 or 2 per year in 62.86% of patients [7] . Montalembert had observed a comparable reduction, with a decrease in seizures to less than 2 per year in 70% of patients [12] . Mellouli et al. in Tunisia had shown even more favorable results, with 55.26% of patients no longer experiencing iterative VCO or recurrent ACS [14] . A recurrence of stroke was observed in one patient, representing 1.67% of cases. This recurrence could be due to poor adherence to treatment or a lack of expected therapeutic response. However, several cases of stroke, sometimes fatal, are reported in the literature in children with sickle cell anemia treated with hydroxyurea [15] - [17] . Which suggests the existence of genetic or epigenetic factors for tolerance or resistance to hydroxyurea that should be explored in other studies with more patients. Regarding the tolerance of hydroxyurea during our study, we did not find any liver damage nor any kidney damage. There was also no myelotoxicity. An important point to highlight is the lack of control of hemoglobin electrophoresis after hydroxyurea administration. Thus, it is difficult to evaluate the direct effect of hydroxyurea on the different hemoglobin fractions of our patients. In reality, the absence of these data could be attributed to several factors. First of all, the financial constraints but also the unavailability of this analysis in certain health structures. In common practice, in our practice contexts, it is the clinical follow-up that is privileged, for the evaluation of the effectiveness of this treatment, on the symptoms of the disease. The monitoring of hematological parameters being more easily done with blood tests. This lack of post-processing data constitutes a significant limitation of our study. Our study strengthened the evidence for the positive effects of hydroxyurea use in children with sickle cell disease. However, further research is needed to better understand the differences in therapeutic response and tolerance from one patient to another but also the mechanism underlying residual complications. This will allow to refine the indications and adapt the dosages for this vulnerable population.

Our study highlights the effectiveness of hydroxyurea and its positive impact in the management of sickle cell patients. The initiation of treatment has significantly reduced the frequency and duration of vaso-oclusive crises, as well as hospitalizations, thus contributing to a significant improvement in the quality of life of patients. However, despite these promising results, challenges persist, particularly regarding understanding and adherence to treatment, as evidenced by the case of stroke recurrence observed in our cohort.