Evaluation of pharmacological efficacy and safety of hydroxyurea in sickle cell disease: Study of a pediatric cohort from Chhattisgarh, India

Abstract

Sickle cell disease (SCD) is a disease of abnormal hemoglobin associated with severe clinical phenotype and recurrent complications. Hydroxyurea (HU) is one of the US-FDA approved and commonly used drug for the treatment of adult SCD patients with clinical ­severity. However, its use in the pediatric groups remains atypical. Despite a high prevalence of the disease in the state Chhattisgarh, there is a lack of evidence supporting its use in pediatric patients. This study aimed to evaluate the pharmacological and clinical efficacy and safety of HU in a large pediatric cohort with SCD from Central India. The study cohort consisted of 164 SCD (138 Hb SS and 26 Hb S beta-thalassemia) children (≤14 years of age) on HU therapy, who were monitored for toxicity, hematological and clinical efficacy at baseline (Pre-HU) and after 24 months (Post-HU). The results highlight the beneficial effects of HU at a mean dose of 18.7 ± 7.0 mg/kg/day. A significant improvement was observed, not only in physical and clinical parameters but also in hematological parameters which include fetal hemoglobin (Hb F), total hemoglobin, hematocrit, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels, when evaluated against the baseline. We did not observe any significant adverse effects during the treatment period. Similar results were obtained on independent analysis of Hb SS and Hb Sβ patients. These findings strengthen the beneficial effect of hydroxyurea in pediatric population also without any serious adverse effects and builds up ground for expanding its use under regular monitoring.

Keywords:

• Fetal hemoglobin
• hydroxyurea
• pediatric cohort
• sickle cell disease
• vaso-occlusive crisis

Acknowledgments

We thank all patients and their family members who participated in this study. The role of hundreds of field volunteers, hospital staff is also gratefully acknowledged.

Conflict of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

The study was supported by the funds from CSIR Sickle Cell Anemia Mission (HCP023), Council of Scientific and Industrial Research (CSIR), Ministry of Science and Technology, Government of India, New Delhi, India.