Clinical Research Directory

Inclusion Criteria: * Age 2yrs to 35yrs * Homozygous hemoglobin S disease or heterozygous hemoglobin SC or S 0/+ * Study specific consent given * Preexisting severe or moderate SCD related complications: * Clinically significant neurological event (stroke) or deficit * Silent crisis, neurocognitive deficit * Pathological angio-MRI with TOF Sequence * TCD velocity \>200 cm/s at 2 occasions \>1 month apart * More than 5 vaso-occlusive crises (VOC) in the past 1 year or more than 20 VOC in a lifetime * Two or more episodes of acute chest syndrome (ACS) in a lifetime or one episode of ACS in the past 24 months * Chronic transfusion requirement or more than 8 transfusions or one exchange transfusion in a lifetime * Transfusion-refractory allo-immunization * More than five SCD-related hospitalizations in a lifetime * Beginning pulmonary hypertension * Osteonecrosis at more than 2 sites * Beginning SCD Nephropathy * Recurrent priapism (\>2) Exclusion Criteria: * Karnofsky or Lansky Performance Score \< 70% * Patients with donor-specific antibodies (DSA) against the potential stem cell donor by either * Cell-based crossmatched assays (Complement-dependent cytotoxicity; CDC) or * Flow cytometry crossmatch test or * Solid-phase immunoassays (SPI) or * Modified SPI such as C4d and C1q assays Whichever method the participating center is experienced in. * Patients with major AB0 incompatibility defined according to EBMT Handbook, Edition 2019 Tab 23.1.: ABO incompatibility Recipient Donor Major O A O B O AB A AB B AB * Cardiac function: * Ejection fraction at rest \<45.0% on echocardiography or * Shortening fraction of \<27.0% by echocardiogram or radionuclide scan (MUGA) * Patients with \> grade II hypertension by Common Toxicity Criteria (CTC) * Renal function: * Estimated creatinine clearance (for patients \> 12 years) greater than 50.0 mL/minute * for pediatric patients (\> 1 year to 12 years), GFR estimated by the updated Schwartz formula ≥ 90.0 mL/min/1.73 m2. If \< 90 mL/min/1.73 m2, renal function must be measured by 24-hour creatinine clearance or nuclear GFR and must be \> 70.0 mL/min/1.73 m2 or * Creatinine clearance below threshold defined for stem cell transplantation according to local clinical standard * Pulmonary function: * DLCO \>50% (adjusted for hemoglobin), and FVC and FEV1≥50%; children unable to perform for PFTs, O2 saturation \<92% on room air. * Liver function: * Total bilirubin \> 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome) and ALT/AST \> 2.5x the upper limit of normal. * Chronic active viral hepatitis * Women who are pregnant (positive serum or urine βHCG) or breastfeeding. Note: Women of childbearing potential must have a negative serum pregnancy test at study entry. * Adults of reproductive potential not willing to use an effective method of birth control during study treatment and for at least 12 months thereafter, * History of uncontrolled autoimmune disease or on active treatment * Patient unable to comply with the treatment protocol * Prior autologous or allogeneic hematopoietic stem cell transplant * Vaccination with a live virus vaccine during the trial * HIV infection * Patients with a history of psychiatric illness or a condition which could interfere with their ability to understand the requirements of the study (this includes alcoholism/drug addiction) * Patients unwilling or unable to comply with the protocol or unable to give informed consent. * Concurrent severe or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which by assessment of the treating physician could compromise participation in the study