Hydroxyurea therapy outcomes in sickle cell children with history of stroke at the University Teaching Hospital Zambia

Abstract

Background :Sickle cell disease (SCD) is the most common debilitating genetic disorder among people of African descent. The most devastating neurologic manifestation of SCD is stroke. Therapeutic studies of hydroxyurea performed in children include investigations indicating hematologic response, lack of significant toxicity, decreases in vaso-occlusive episodes and possible prevention of secondary strokes. However, most treatment recommendations for the management of SCD are based on studies conducted in resource-rich countries and not the resource limited regions which are most affected. The objective of the study was to assess the hydroxyurea (HU) therapy outcomes in SCD children with history of stroke at University Teaching Hospital (UTH)-Zambia. Design and site :Retrospective cohort study conducted at the UTH-Zambia. :Methods Clinical and laboratory data was analyzed in 34 patients. Changes in hematological parameters during HU therapy were abstracted from the patient files. Vaso occlusive crisis (VOC) episodes, number of hospital inpatient days and stroke episodes 6 months before and 6 months after initiation of HU were also captured. Results :The mean dose of HU was 10.45 mg/kg/day. There was no significant increase in the red blood cell indices at 6 months of therapy. Mean hemoglobin changed from 7.18 g/dl to 7.11g/dl, P = 0.8443 and the mean MCV (mean capsular volume) changed from 92.51fl to 95.08 fl, P = 0.2982. There were however, significant reductions in the number of vaso occlusive episodes, number of hospital stay and number of stroke episodes after initiation of HU therapy. The ratio of VOC reduced from 0.337/day to 0.093/day, P=0.00001, the ratio of hospital stay reduced from 5.012 to 0.578, P = 0.0004 where as the stroke incidences reduced from 0.149/day to 0.005/day, P = 0.00001 after initiation of HU therapy. There was no significant decrease in the mean white blood cell (WBC) and platelet count at 6 months on HU therapy. Mean WBC changed from 22.63 x 109/l to 22.35 x 109/l, P = 0.9479 and mean platelets from 434.74 x 109/l to 386.94 x 10 9 /l, P = 0.2634. A number of positive correlations were found between dose and therapeutic response. The pearson’s correlation coefficient between HU dose of <15mg/kg/day and change in hospital inpatient days was 0.0564 where as between HU dose of <15mg/kg/day and stroke recurrence is 0.1665. The pearson’s correlation coefficient between HU dose of 15-30mg/kg/day and change in hospital inpatient day was 0.1197. Conclusion :The study shows that at the mean dose of 10.45mg/kg/day, sickle cell children with history of stroke at the University Teaching Hospital presented with significant reductions in the number of inpatient hospital days and in the number of stroke recurrences. The study results reviewed no HU hematological toxicity, however, at this mean HU dose; there was no hematological therapeutic response. The study results also indicated a positive correlation between dose and the HU therapeutic response. Beneficial effects of HU therapy are achieved with HU dose of <15mg/kg/day although hematological therapeutic response is not achieved at this dose.