Minireview: Prognostic factors and the response to hydroxurea treatment in sickle cell disease

Abstract

This review describes current considerations in the use of hydroxyurea for the management of sickle cell disease in the context of clinical severity. Randomized trials of hydroxyurea have generally enrolled subjects with increased severity based on frequent vaso-occlusive events. An exception was the BABY HUG study in infants which documented substantial benefit even for asymptomatic subjects. Increasing data indicate that hydroxyurea has a substantial effect on reducing mortality in both adults and children-perhaps the most compelling reason for advocating the drug's widespread use. Although the efficacy of hydroxyurea is mediated primarily through increased erythrocyte fetal hemoglobin and much has been learned about the genomic influences on fetal hemoglobin levels in sickle cell disease, our ability to predict the fetal hemoglobin response to hydroxyurea remains limited; much more work in this area is indicated. The review is concluded with the recommendations of the 2014 NIH Evidence-Based Management of Sickle Cell Disease Expert Panel Report.

Vital Signs: Use of Recommended Health Care Measures to Prevent Selected Complications of Sickle Cell Anemia in Children and Adolescents — Selected U.S. States, 2019

“…Finally, because hydroxyurea use was defined by the filling of a single prescription, the findings overestimate ongoing hydroxyurea use. TCD screening is critical to stroke prevention in children and adolescents with SCA (7); hydroxyurea is efficacious in preventing serious complications (8), and numerous studies demonstrate the safety of its long-term use (20). The findings from this study highlight that health care for children and adolescents with SCA is fragmented.…”

“…Chronic blood transfusion therapy, the recommended intervention, substantially reduces stroke occurrence in children and adolescents identified as being at risk (7). The panel also recommended that children and adolescents aged ≥9 months with SCA (including asymptomatic children) be offered treatment with hydroxyurea, a medication shown to be efficacious in preventing or reducing severe pain episodes, acute chest syndrome, and other SCA-associated complications and increasing patient survival (8). Although the panel chose to recommend offering treatment as a means of opening discussion with families, it emphasized that an established evidence base supported the sustained benefits of hydroxyurea therapy for young persons with SCA without harmful effects on growth, development, female fertility, or increased risks for genetic mutations or cancer (5).…”

Enhancing the care of patients with sickle cell disease

“…Hydroxyurea has been successful in reducing mortality in adults and children, the number of painful vaso-occlusive crises, and cases of acute chest syndrome (Wang 2016). However, it remains underused, primarily because it has the potential to cause teratogenic fetal malformations (Ballas et al 2012).…”

Influence of Study Design on Developmental and Reproductive Toxicology Study Outcomes

“…In this approach, exposure of pregnant dams could be commenced later in gestation to overcome early fetal loss due to a potent developmental toxicant and yet still have sufficient animals available to continue postnatal evaluations. NTP has applied such an approach in the study of hydroxyurea, the only Food and Drug Administration–approved medication for sickle cell disease in adults that also appears to have efficacy in infants and children (Wang 2016), but for which information on potential long-term consequences would be helpful to clinicians to evaluate the benefits of treatment in comparison to risk. The last option always available is to undertake separate studies.…”