Fetal Hemoglobin Levels in African American and Hispanic Children With Sickle Cell Disease at Baseline and in Response to Hydroxyurea

Abstract

The degree of fetal hemoglobin (HbF) expression is a major determinant of phenotypic severity of sickle cell disease (SCD). Genetic regulation of HbF production is complex and can vary among ethnic groups. The pediatric sickle cell population at our institution is approximately half Hispanic, nearly all from the Dominican Republic. Hydroxyurea (HU) is the only FDA-approved drug to ameliorate symptoms of SCD. We retrospectively compared baseline and HU-induced %HbF in African American (AA) and Hispanic (H) patients aged 4–21 years with HbSS or HbSβ0Thalassemia. No significant differences were detected in average baseline %HbF between AA (N=48) and H (N=58) patients (p=0.63). In the subset of children taking hydroxyurea who reached maximum tolerated dose (MTD), no differences were found between the ethnic groups in laboratory response to drug, measured by %HbF at MTD (p=0.28), the increase in %HbF (p=0.31) or mean red cell volume (MCV) (p=0.93), or the MTD of HU (p=0.95). Regulation of HbF at baseline and in response to HU are comparable between Hispanics and African Americans at our center. If generalizable, our results support combining these two groups in future clinical and translational analyses focused on HbF and response to HU in this ethnically-mixed patient population.

Sickle cell in sickle cell disease in Latin America and the United States

“…HbF generally ranges from 2-20% in children with SCD [8,41,42]. Similar HbF levels have been reported across diverse groups from pediatric cohorts from Brazil, African Americans, and a Hispanic cohort in New York [41][42][43][44]. Among the ameliorative effects of hydroxyurea on SCD, a major impact is its induction of HbF [40].…”

“…Fetal hemoglobin (HbF) level is a highly regulated modifier of SCD disease, with an inverse association with risk of severe complications [38][39][40]. HbF generally ranges from 2-20% in children with SCD [8,41,42]. Similar HbF levels have been reported across diverse groups from pediatric cohorts from Brazil, African Americans, and a Hispanic cohort in New York [41][42][43][44].…”

“…Among the ameliorative effects of hydroxyurea on SCD, a major impact is its induction of HbF [40]. Children in Brazil had HbF levels at baseline and with hydroxyurea induction [8] that were similar to those reported for an African American and Latino SCD clinic population in New York [42]. Only scant data have been reported on HbF and hydroxyurea response from other Latin American countries.…”

Candidate Sequence Variants and Fetal Hemoglobin in Children with Sickle Cell Disease Treated with Hydroxyurea

“…Children with sickle cell disease generally have higher baseline HbF levels than adults and more pronounced HbF response to hydroxyurea [5], [6], [7], [8], [9], [11], [13], [16], [18], [19], [20], [26]. Findings from this multi-site, observational analysis corroborate in children the correlation between baseline and hydroxyurea-induced HbF levels [18], [19], and demonstrate that one third of the variance in induced HbF is attributable to baseline levels.…”

Study protocol for a randomized controlled trial to assess the feasibility of an open label intervention to improve hydroxyurea adherence in youth with sickle cell disease

“…Columbia Pediatric SCD clinic provides care to approximately 200 youth, with approximately one third of youth age 10–17 years currently on HU therapy. Approximately half of youth at the Columbia site are Hispanic, primarily from the Dominican Republic [59]. Some parents speak Spanish as a primary language.…”