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

This is an interventional treatment trial for HbS Disease Read More

Inclusion Criteria:

• Age 1yr 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