Abstract
Introduction
Approximately 2000 babies are born with sickle cell disease annually in the US. Children with severe forms of sickle cell disease (SCD), such as Hemoglobin SS and Hemoglobin S beta 0 thalassemia (Sbeta0), are at risk for severe anemia, vasoocclusive pain crisis, acute chest syndrome, splenic sequestration, central nervous system ischemia, and shortened life expectancy. The drug Hydroxyurea (HU) increases Hgb F, is effective in ameliorating many sickle cell symptoms, and improves survival. Safety and efficacy of HU in children and infants have been demonstrated.
Methods
Following publication of the BABY HUG trial results in 2011, the Comprehensive Pediatric Sickle Cell Program of Northern Virginia implemented HU initiation for all infants with Hgb SS or Hgb Sbeta0. HU was prescribed at age 6-7 months for 2 patients and at 9-12 months of age for 22 patients. HU dosage was diligently adjusted at clinic visits to maximize Hgb F. An IRB-approved prospective, longitudinal database was launched to follow each patient's clinical course and outcome in 6-month increments. Data are reported for children born after January 2011 who were started on HU by 12 months of age, followed on HU therapy continuously in this clinic, and were at least 2 years of age by June 2018.
Results
All 24 children in the analysis have Hgb SS. Sixteen children have been followed for 3 years or more, 11 children have been followed for 4 years or more, 7 children have been followed for 5 years or more, 4 children have been followed for 6 years or more, and 3 children have been followed for 7 years. Average Hgb at 6 months of age was 9.5 g/dL, and ranged between 9.5 and 10.7 g/dL for age 1-7. Average Hgb F was 34.1% at 6 months of age and dipped to 29.1% at 1 year of age, but was maintained above 30% from age 1.5 - 3 years and at 27.8% - 30.5% for age 3.5 - 7 years. For a total of 92 person-years, there were 27 hospitalizations, all within the first 3 years of life. 20/27 (74%) hospitalizations were for fever, pneumonia without hypoxia or need for transfusion, or other infections, 5/27 (19%) were for splenic sequestration, and only 1/27 (4%) hospitalization was for pain that occurred before HU initiation. ED visits totaled 68, 53/68 (78%) were for fever and 47/68 (69%) occurred in the first 3 years of life. Only 2/68 (3%) ED visits were attributed to dactylitis/pain, occurring prior to HU initiation. ED visits after age 3 were all for fevers. The most common complication specific to sickle cell disease was splenic sequestration, which is not preventable by HU. All 4 transfusions given were for splenic sequestration.
Conclusion
Continuous tracking in a single center observational study demonstrated that continuous HU therapy starting in infancy maintained Hgb and Hgb F at or above pre-HU levels into childhood, is associated with no hospitalizations after age 3 and no ED visits for pain after HU initiation by age 1. No acute chest syndrome requiring oxygen or transfusion, no abnormal or conditional TCD, and no overt strokes occurred in this cohort. Implementation of HU for children with sickle cell disease starting in infancy is feasible in the community and is effective in maintaining high fetal hemoglobin and preventing disease complications.
No relevant conflicts of interest to declare.
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