Haploidentical Bone Marrow Transplantation in Sickle Cell Patients (BMTCTN1507)

Inclusion Criteria

Adequate physical function as measured by all of the following:

• A Karnofsky/Lansky performance score of ≥ 60.
• Cardiac function: Left ventricular ejection fraction (LVEF) > 40%; or LV shortening fraction > 26% by cardiac echocardiogram or by Multi Gated Acquisition Scan (MUGA) scan.
• Pulmonary function: Pulse oximetry with a baseline O2 saturation of ≥ 85% and Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% (corrected for hemoglobin).
• Renal function: Serum creatinine ≤ 1.5 x upper limit of normal for age and estimated or measured creatinine clearance ≥ 70 mL/min/1.73 m²
• Hepatic function:
• Serum conjugated (direct) bilirubin 185 cm/sec plus evidence of intracranial vasculopathy.
• Silent Cerebral Infarct defined as an infarct-like lesion based on an MRI signal abnormality at least 3 mm in one dimension and visible in two planes on FLAIR or T2-weighted images (or similar image with 3D imaging) and documented neurological examination performed by a neurologist demonstrating the participant has a normal neurologic examination or an abnormality on examination that could not be explained by the location of the brain lesion(s).
• Acute severe vaso-occlusive pain episodes requiring hospitalization and recalcitrant to maximum medical therapy. Episodes of pain to be adjudicated by selected committee.
• One acute chest syndrome episode resulting in intensive care admission requiring non-mechanical ventilatory support: simple nasal cannula, face mask that requires oxygen content (venti mask, non-rebreather), simple nasal cannula, face mask O2(e.g. ventimask, rebreather), CPAP, SiPAP, BiPAP, high flow nasal cannula (HFNC) or invasive mechanical ventilatory support (delivered by ETT or trach).
• Right heart catheterization confirmed pulmonary artery pressure >25 mmHG or mean pulmonary vascular resistance 206(57-421) dyn·s·cm-5
• Essential hypertension on antihypertensive medications >95% upper limit of normal age (as defined according to the American Academy of Pediatrics)
• Recurrent priapism (episodes lasting at least 4 hours at least twice in the last 12 months or 3 times in the last 24 months) recalcitrant to medical treatment or unable to use hydroxyurea due to SCD phenotype with the approval of the adjudication committee

Inclusion Criteria for Stratum 2: Adults Ages 15.00 - 45.99 at enrollment

Participants with sickle cell anemia (Hb SS or Sß° Thalassemia) who are 15.00 - 45.99 years of age at enrollment AND who have one or more of the following:

• Age 15.00 - 45.99 years at Segment A enrollment
• Participants with sickle cell anemia (Hb SS or Sß° Thalassemia) who have one or more of the following:
• A neurological event resulting in focal neurologic deficits that lasted ≥ 24 hours (classical clinical definition of stroke, not requiring imaging studies of the brain) OR a focal neurological event resulting in abnormalities on T2-weighted or FLAIR images using a MRI scan, indicative of an acute infarct, with no other reasonable medical explanation (definition of a stroke supported with MRI imaging scans of the brain), OR both.
• History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea);
• History of three or more severe vaso-occlusive pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea); painful episodes related to priapism, osteonecrosis or any sickle-related complication are acceptable;
• Administration of regular RBC transfusion therapy, defined as receiving ≥8 packed red blood cell transfusions per year for ≥1 year in the 12 months before enrollment to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome);
• An echocardiographic finding of tricuspid valve regurgitan