|Linda Fukas, RN, BSN|
1 United States site
> 18 Years
Hb SS, Hb SC, Hb AS
Early Phase 1
– Patient selection
1. Age > 18 years
2. Patients with Hb SS, Hb SC, Hb Sβ0 genotype
3. Presence of at least 1 of the following manifestations:
1. History of clinically significant neurologic event defined as stroke or any
neurological deficit lasting > 24 hours.
2. History of two or more episodes of acute chest syndrome (ACS) in the 2-year
period preceding enrollment despite the institution of supportive care
3. Three or more pain crises per year in the 2-year period preceding referral
(required intravenous pain management in the outpatient or inpatient
This may include painful episodes related to priapism, osteonecrosis or any
4. An echocardiographic finding of the tricuspid valve regurgitant jet (TRJ)
velocity ≥ 2.7 m/sec.
5. History of osteonecrosis or avascular necrosis of ≥ 2 joints
6. Administration of regular RBC transfusion therapy, defined as receiving 8 or
more transfusions per year for > 1 year to prevent vaso-occlusive clinical
complications (i.e. pain, stroke, and acute chest syndrome)
7. History of RBC allo-immunization but without detectable allo-antibodies.
8. Evidence of sickle hepatopathy or iron overload in patients who received ≥ 8
packed RBC transfusions for ≥ 1 year or have received ≥ 20 cumulative packed
RBC transfusions. These patients will undergo MRI of the liver to estimate
liver iron content.
9. Patients with hepatic iron content of ≤ 7 mg Fe/ gm of liver will be
included ii. Patients with hepatic iron content of ≥ 7 mg Fe/ gm of liver
will undergo biopsy to look for absence of histological findings suggestive
of cirrhosis, fibrosis and active hepatitis
h. Sickle nephropathy defined as Cr ≥ 1.5 times the ULN or biopsy proven
i.Reversible SCD complication not ameliorated by hydroxyurea: i.Two or more
vaso-occlusive crises requiring hospitalizations ii. Any episode of ACS while on
4. Adequate physical function as measured by all of the following:
1. Karnofsky performance score > or equal to 70
2. Cardiac function: Left ventricular ejection fraction (LVEF) > 40%; or LV
shortening fraction > 26% by cardiac echocardiogram or by MUGA scan.
3. Pulmonary function: Pulse oximetry with a baseline O2 saturation of > 85%,
DLCO > 40% (corrected for hemoglobin).
4. Renal function: Serum creatinine ≤ 1.5 x the upper limit of normal for age
as per local laboratory and 24 hour urine creatinine clearance >70
mL/min/1.73 m2; or GFR > 70 mL/min/1.73 m2 by radionuclide GFR unless reason
for transplant is sickle nephropathy
5. Hepatic function:
i. Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory; ii. ALT and AST < 5 times upper limit of normal. iii. Patients with hyperbilirubinemia because of hyper hemolysis, or who experience a sudden, profound change in the serum hemoglobin after a RBC transfusion are not excluded. 5. The HLA matched related donor must be willing to donate and must meet our institutional guidelines to donate peripheral blood stem cells 6. Absence of donor specific HLA antibodies. 7. Absence of clinical or radiographic evidence of neurologic event within 6 months prior to proceeding with transplantation. 1. Cerebral MRI/MRA within 6 months prior to initiation of transplant conditioning. 2. If patient has a neurologic event such as stroke or transient ischemic attack during recruitment process, patient will be deferred for 6 months before reconsideration. Donor selection 1. Siblings who are ≥18 years and capable and willing to donate PBSC 2. Sibling donors are HLA-matched. HLA-A, B, C, and DRB1 match based on high-resolution typing 3. All sibling donors MUST meet institutional criteria for donation. 4. Donors with sickle cell trait (Hb AS) are permitted. 5. Donors with ABO minor incompatibility are permitted
1. Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
2. Seropositivity for HIV.
3. Previous stem cell transplantation.
4. Participation in a clinical trial in which the patient received an investigational
drug or device
5. A history of substance abuse as defined by version IV of the Diagnostic & Statistical
Manual of Mental Disorders (DSM IV).
6. Demonstrated lack of compliance with prior medical care as determined by referring
7. Pregnant or breast-feeding females.
8. Unwillingness to use approved contraception method from time of conditioning regimen
and 4 months after discontinuation of all immunosuppressive medications.
1. Donors with hemoglobinopathies: Hb SS, Hb SC, Hb Sβ0 and all other unstable
2. Presence of anti-donor HLA antibodies in the recipient
3. Donors with major ABO incompatibility
4. Donors who are HIV-1, HIV-2, HTLV-1, HTLV-2 seropositive or with active hepatitis B or
hepatitis C virus infection