Inclusion Criteria: * Diagnosis of sickle cell disease with the homozygous HbS homozygous genotype (HbSS) or an HbSβ thalassemia variant (ie, HbSβ0 thalassemia or HbSβ+ thalassemia) genotype, confirmed by hemoglobin studies. * Fetal hemoglobin (HbF) ≤ 15%. * Severe sickle cell disease symptomatology, defined as any one or more of the following: 1. ≥ 2 episodes of acute chest syndrome in the last 2 years. 2. ≥ 3 episodes of severe pain events requiring a visit to a medical facility and treatment with opioids in the last 2 years. 3. \> 2 episodes of recurrent priapism in the last 2 years. 4. Red-cell alloimmunization (\> 2 antibodies) during long-term transfusion therapy (lifetime history). 5. Chronic transfusions for primary or secondary prophylaxis (lifetime history). 6. Trans-thoracic echocardiograph evidence of tricuspid valve regurgitant jet velocity ≥ 2.7 m/sec (lifetime history). 7. Clinically significant neurologic event (eg, ischemic stroke) or any neurological deficit lasting \> 24 hours. * Not eligible for human leukocyte antigen (HLA)-matched hematopoietic stem cell transplantation, defined as follows: no medically eligible, available, and willing 10/10 matched HLA-identical sibling donor, unless subject has declined this treatment option (as documented in the informed consent form). * Not eligible for, declined, or, as judged by the investigator, failed therapy with hydroxyurea and if still on hydroxyurea is able to interrupt hydroxyurea starting at the beginning of the transfusions, before mobilization and apheresis. Exclusion Criteria: * Hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficiency. * Thiopurine S-methyltransferase (TPMT) deficiency. * Alpha thalassemia. * Inadequate bone marrow function, defined as at least 1 of the following: 1. Absolute neutrophil count \< 1000/µL. 2. Platelet count \< 120,000/µL.