No abstract

Transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are the most common inherited hematologic disorders, affecting approximately 60,000 and 300,000 patients worldwide, respectively. Current therapies, including red blood cell (RBC) transfusion and iron chelation in TDT and transfusion, pain management, and hydroxyurea in SCD, help to manage the disorders but do not address the underlying cause. Drug therapies, such as crizanlizumab and luspatercept, have also helped to reduce the need for transfusion in TDT patients and the incidence of vaso-occlusive episodes in SCD patients. Allogeneic bone marrow transplantation may be a curative option, but finding an appropriate donor is difficult. An association has been observed between elevated levels of fetal hemoglobin and improved morbidity and mortality in these patients. Downregulating BCL11A, a transcription factor that blocks fetal hemoglobin in erythroid cells, may help to increase fetal hemoglobin levels and improve outcomes. Using the CRISPR-Cas9 gene-editing technique, CTX001, an investigational drug, was infused in 2 patients. This article describes the results of infusing CTX001 in 1 patient with TDT and another with SCD.