13 Years - 40 Years
A diagnosis of sickle cell disease with genotype HbSS or HbS/β0 thalassemia.
Between the age of 13-40 years.
Clinically severe disease, defined as at least 4 vaso-occlusive events (VOEs) within the past 24 months prior to consent.
Adequate hematologic parameters (regardless of therapy) including white blood cell (WBC) count within the range of 2.5 – 25.0 x 10^9 /L, hemoglobin within the range of 5 – 11 g/dL, and platelet count above 150 x 10^9 /L
Adequate organ function and performance status:
Karnofsky/Lansky performance status ≥80%.
Serum creatinine /= 60 mL/min/1.73 m2.
Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value <3× the upper limit of normal (ULN). DLCO, FEV1, and FVC >50% of predicted
Left ventricular ejection fraction >40% or shortening fraction >25%
No HLA-genotypically identical related bone marrow donor available.
Parental/guardian/patient signed informed consent.
Subjects who have:
Concomitant condition or illness including: ongoing or active infection, active malignancy, major surgery in the past 30 days, medical/psychiatric illness/social situations that would limit compliance with study requirements as determined by the treating physician.
Receiving a chronic transfusion regimen for primary or secondary stroke prophylaxis. (Note: patients with a history of abnormal TCD who have transitioned from transfusions to hydroxyurea for stroke prophylaxis are also not eligible for the study.)
Patients with history of abnormal TCD (measured with a timed average maximum mean velocity of ≥200 cm/second in the terminal portion of the internal carotid or proximal portion of middle cerebral artery or if the imaging TCD method is used, >185 cm/second plus evidence of intracranial vasculopathy) who were ever on transfusions and subsequently transitioned to hydroxyurea.
History of overt stroke or any neurologic event lasting >24 hours. (Note: patients with imaging evidence of silent stroke but not on a chronic transfusion regimen are not excluded.)
Isolated recurrent priapism unresponsive to medical and surgical therapies in the absence of other qualifying VOE complications that meet