Chronic Administration of Hydroxyurea (HU) Benefits Caucasian Patients with Sickle-Beta Thalassemia.

Rosario Di Maggio,Aurelio Maggio,Giuseppina Calvaruso,Xiongce Zhao,Matthew Hsieh,Paolo Rigano,Disma Renda,John Tisdale

doi:10.3390/ijms19030681

Abstract

In sickle cell disease (SCD), hydroxyurea (HU) treatment decreases the number of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) by increasing fetal hemoglobin (HbF). Data are lacking regarding the frequency of HU dose modification or whether sub-therapeutic doses (<15 mg/kg/day) are beneficial. We reviewed the medical records of 140 patients from 2010 to 2014. The laboratory parameters and SCD complications were compared between the first and last visits based on HU use. Fifty patients (36%) never took HU or suspended HU (“no HU” group). Among patients taking <15 mg/kg/day HU on their first visit, half remained at the same dose, and the other half increased to ≥15 mg/kg/day. Among patients taking ≥15 mg/kg/day, 17% decreased to <15 mg/kg/day, and 83% stayed at ≥15 mg/kg/day. The “no HU” group had fewer episodes of VOC and ACS. Both HU treatment groups had a reduction in both complications (p < 0.0001). This improvement was observed in all SCD phenotypes. The white blood cell (WBC) counts were found to be lower, and HbF increased in both HU groups (p = 0.004, 0.001). The maximal HbF response to HU in HbS/β+-thalassemia was 20%, similar to those observed for HbSS (19%) and HbS/β0-thalassemia (22%). HbS/β+-thalassemia could have a similar disease severity as HbSS or HbS/β0-thalassemia. Patients with HbS/β0-thalassemia or HbS/β+-thalassemia phenotypes responded to HU.

Highlights

Sickle cell disease (SCD) is the most common inherited hemoglobin disorder in Africa and has prompted the World Health Organization (WHO) to call for the implementation of regional strategies to increase disease awareness and provide a national infrastructure to reduce its morbidity and mortality [1]
We evaluated the effects of different HU doses in patients with SCD in terms of hematologic improvement, possible changes in organ dysfunction, and causes of death at a single referral institution
The criteria to start HU treatment were those suggested by Charache et al, 1995 (>3 painful vaso-occlusive crises per year and/or >2 Acute Chest Syndrome [20])

Summary

Introduction

Sickle cell disease (SCD) is the most common inherited hemoglobin disorder in Africa and has prompted the World Health Organization (WHO) to call for the implementation of regional strategies to increase disease awareness and provide a national infrastructure to reduce its morbidity and mortality [1]. Childhood deaths have declined over the last 3 decades in Europe and North America due to newborn screening, routine prophylaxis with penicillin, pneumococcal vaccinations, and access to medical care [5,6,7,8]. Despite these advances, mortality due to disease and organ dysfunctions has remained high in patients with SCD. The median age of death was reported to be 42 years for men and 48 years for women [9,10]

Methods

Results

Conclusion