Immune Suppression Before Stem Cell Transplant for Sickle Cell Disease or Thalassemia

Who can take part

• Age ≥ 2 and ≤ 50 years
• Suitable haploidentical donor
• Performance score ≥ 70% by Karnofsky Performance Scale or 0 to 1 by ECOG (age > 16 years), or Lansky Play-Performance Scale ≥ 70% (age ≤ 16 years)
• Adequate major organ system function as demonstrated by:; For patients ≥ 18 years of age:; eGFR ≥ 50 mL/min by Cockcroft-Gault formula Formula: ((140 - Age) x Weight (kg)) / (72 x Serum Creatinine (mg/dL) Female Adjustment: Multiply result by 0.85; For patients < 18 years of age:; Serum creatinine clearance: glomerular filtration rate [GFR]) must be >50 mL/min/1.73 m2 as calculated by the Schwartz formula
• Conjugated (direct) bilirubin less than 3x upper limit of normal
• ALT or AST ≤ 3 times institutional upper limit of normal
• Left ventricular ejection fraction ≥ 50%
• Diffusing capacity for carbon monoxide (DLCO) ≥ 50% predicted, corrected for hemoglobin. For children < 7 years of age who are unable to perform PFT, oxygen saturation > 92% on room air by pulse oximetry
• For SCD patients: HbSS, HbSC, HbS/β° with one or more of the following complications:; Acute chest syndrome: 2 or more episodes in the 2 years preceding enrollment; Vaso-occlusive episodes: 3 or more episodes in the 2 years preceding enrollment; Recurrent priapism: 2 or more episodes in the 2 years preceding enrollment; History of osteomyelitis or osteonecrosis; Cerebrovascular disease:
• Imaging evidence of prior overt or silent stroke
• History of a neurologic event resulting in focal neurologic deficits lasting > 24 hours
• Abnormal transcranial Doppler: Timed average maximum mean velocity ≥ 200 cm/sec in terminal portion of the carotid or proximal portion of the middle cerebral artery or > 185 cm/sec plus evidence of intracranial vasculopathy if imaging TCD is used; Pulmonary hypertension: Confirmed by right heart catheterization with mean pulmonary arterial pressure ≥ 25 mmHg or mean pulmonary vascular resistance > 2 Wood units; Red blood cell alloimmunization (> 3 alloantibodies)
• For thalassemia patients: Any genotype, with all of the following:; Onset of red blood cell transfusion dependence during the first 3 years of life; RBC transfusion history > 225 mL/kg/year or > 15 lifetime RBC transfusions; Pre-transfusion hemoglobin ≤ 7 g/dL; Hepatosplenomegaly
• Patient or the patient's legal representative, parent(s) or guardian should be able to provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years
• For sexually active men and women of childbearing potential, must agree to use a form of contraception considered effective and medically acceptable by the Investigator

Who cannot take part

• Prior myeloablative allogeneic HCT
• Positive pregnancy test in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization
• Inability to comply with medical therapy or follow-up
• Overt stroke or CNS instrumentation (e.g. for Moyamoya disease) within 6 months of enrollment
• Active hepatitis B or C
• Other uncontrolled infections
• Other malignancy/cancer diagnosis unless in remission after definitive therapy for a minimum of 2 years. Exceptions: Ductal carcinoma in situ, basal cell carcinoma, cervical intraepithelial neoplasia
• Known history of allergic reactions to any constituents of the stem cell product, including a known history of allergic reactions to DMSO
• Liver cirrhosis. Mild fibrosis will be permitted, i.e. fine reticulin or grade 1 of 4, with bridging fibrosis
• Hepatic iron content ≥ 3 mg Fe/g liver dry weight, if applicable