Abstract
Sickle cell disease (SCD) is characterized by variable clinical outcomes, with some patients suffering life-threatening complications during
childhood, and others living relatively symptom-free into old age. Because of this variability, there is an important potential role for precision
medicine, in which particular different treatments are selected for different groups of patients. However, the application of precision
medicine in SCD is limited by difficulties in identifying different prognostic groups and the small number of available treatments. The main
genetic determinant of outcomes in SCD is the underlying β-globin genotype, with sickle cell anemia (HbSS) and hemoglobin SC disease
(HbSC) forming the 2 major forms of the disease in most populations of African origin. Although there are clear differences in clinical outcomes
between these conditions, treatments approaches are very similar, with little evidence on how to treat HbSC in particular. Other
genomic information, such as the co-inheritance of α-thalassemia, or high fetal hemoglobin (HbF) levels, is of some prognostic value but
insufficient to determine treatments. Precision medicine is further limited by the fact that the 2 main drugs used in SCD, penicillin and
hydroxyurea, are currently recommended for all patients. Newer treatments, such as crizanlizumab and voxelotor, raise the possibility
that groups will emerge who respond best to particular drugs or combinations. Perhaps the best current example of precision medicine
in SCD is the selective use of blood transfusions as primary stroke prevention in children with evidence of cerebral vasculopathy. More
precise treatments may emerge as we understand more about the pathology of SCD, including problems with erythropoiesis.
childhood, and others living relatively symptom-free into old age. Because of this variability, there is an important potential role for precision
medicine, in which particular different treatments are selected for different groups of patients. However, the application of precision
medicine in SCD is limited by difficulties in identifying different prognostic groups and the small number of available treatments. The main
genetic determinant of outcomes in SCD is the underlying β-globin genotype, with sickle cell anemia (HbSS) and hemoglobin SC disease
(HbSC) forming the 2 major forms of the disease in most populations of African origin. Although there are clear differences in clinical outcomes
between these conditions, treatments approaches are very similar, with little evidence on how to treat HbSC in particular. Other
genomic information, such as the co-inheritance of α-thalassemia, or high fetal hemoglobin (HbF) levels, is of some prognostic value but
insufficient to determine treatments. Precision medicine is further limited by the fact that the 2 main drugs used in SCD, penicillin and
hydroxyurea, are currently recommended for all patients. Newer treatments, such as crizanlizumab and voxelotor, raise the possibility
that groups will emerge who respond best to particular drugs or combinations. Perhaps the best current example of precision medicine
in SCD is the selective use of blood transfusions as primary stroke prevention in children with evidence of cerebral vasculopathy. More
precise treatments may emerge as we understand more about the pathology of SCD, including problems with erythropoiesis.
| Original language | English |
|---|---|
| Journal | HemaSphere |
| Publication status | Published - 6 Jul 2022 |
