A Trial to Assess Haploidentical T-depleted Stem Cell Transplantation in Patients With SCD

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