Inclusion Criteria:

The following criteria are established to identify subjects with sickle cell disease (SCD)
who have a high predicted morbidity and are at risk for early mortality. Subjects with
S/S disease, S/C disease, Hemoglobin H disease, Alpha Thalassemia Major, Thalassemia Major
(also known as Cooley's anemia) or S/B* thalassemia and one or more of the following
medical complications will be eligible:

- History of impaired neurological function and/or findings on Magnetic Resonance Image
(MRI)/Magnetic Resonance Angiogram (MRA) that are associated with sickle cell disease

- More than 1 episode of acute chest syndrome with stage I or II pulmonary disease

- Osteonecrosis involving ≥ 2 joints

- Sickle cell nephropathy as evidenced by a glomerular filtration rate of 30% - 50% of
the predicted normal

- Alloimmunization that is sufficient to interfere with the efficacy of chronic
transfusion therapy

- Chronic or recurrent priapism

- Major visual impairment in one or both eyes with bilateral proliferative retinopathy

- Persistent disabling pain (≥ 2 episodes per year) despite trials of chronic
transfusion and/or hydroxyurea at recommended doses for at least 6 months duration

Additional General Criteria:

Subjects must also meet all of the following general inclusion criteria:

- Subjects must have a related donor (identical or mismatched for 1, 2 or 3 HLA- A,
HLA-B or HLA-DR loci).

- Subjects must have adequate cardiopulmonary function as documented by a left
ventricular ejection fraction ≥ 50% (or within normal limits per Institutional
criteria) or a left ventricular shortening fraction Within normal limits (WNL) per
Institutional criteria, without inotropic support. If Ejection fraction is 40-50%,
the patient may be considered for participation if cleared by a Cardiologist.

- Subjects must have adequate pulmonary function as documented by Diffusing capacity of
the lung for carbon monoxide (DLCO) and Forced expiratory volume in 1 second (FEV1)

- 50% predicted for age and size. If DLCO and FEV1 are between 40-50%, patient
may be considered for participation if cleared by a Pulmonologist.

- Subjects must have adequate hepatic function as demonstrated by a serum albumin ≥ 3.0
mg/dL, and serum glutamic pyruvic transaminase (SGPT) or serum glutamic oxaloacetic
transaminase (SGOT) ≤ 2.5 times the upper limit of normal.

- Subjects must have adequate renal function as demonstrated by a serum creatinine ≤
1.5 mg/dL. If serum creatinine is ≥ 1.5 mg/dL, then a creatinine clearance test must
be done and the result 50% of normal.

- Subjects or legal guardians must give written informed consent, and subjects must
assent where age and intellectually appropriate.

- There are no age limits for this protocol.

Exclusion Criteria:

- Uncontrolled infection or severe concomitant diseases, which in the judgment of the
Principal Investigator, could not tolerate transplantation.

- Severe impairment of functional performance as evidenced by a Karnofsky (patients ≥16
years old) or Lansky (children <16 years old) score <70%

- Stage III or IV sickle cell pulmonary disease

- Renal insufficiency (GFR < 25% of predicted normal for age)

- Subjects with a positive human immunodeficiency virus (HIV) antibody test result

- Subjects who are pregnant, as indicated by a positive serum human chorionic
gonadotrophin (HCG) test

- Subjects of childbearing potential who are not practicing adequate contraception as
defined by the investigator at the site

- Subjects must not have had previous radiation therapy that would preclude total body
irradiation (as determined by a radiation oncologist).