Haplo T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease

Familial Haploidentical T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease (IND 14359)

This study is being done to determine the safety and outcome (long-term control) of a high-dose chemotherapy regimen followed by an infusion of CD34 selected (immune cells) stem cells from a partially matched adult family member donor, called haploidentical stem cell transplantation, in high-risk sickle cell disease patients.

Funding Source - FDA OOPD

The purpose of this study is to investigate host myeloimmunosuppressive conditioning followed by familial haploidentical T cell depleted allogeneic stem cell transplantation in patients with high risk Sickle Cell Disease (SCD). It is hypothesized that it will be safe and well tolerated, and result in sustained donor chimerism, acceptable engraftment and immune reconstitution. Also, that it will limit SCD related organ damage resulting in improved and/or stable neurological, neurocognitive, pulmonary and pulmonary vascular function and health related quality of life (QOL).

Patients 2-20.99 years of age with a diagnosis of high-risk SCD and with an unaffected HLA partially matched family donor and meeting eligibility criteria (inclusion and exclusion criteria) are eligible.

Inclusion Criteria:

• Homozygous Hemoglobin S Disease, or Hemoglobin S Beta0/+ thalassemia

• Patients must demonstrate one or more of the following Sickle Cell Disease Complications

  1. Clinically significant neurologic event (stroke) or any neurologic deficit lasting >24 hours that is accompanied by an infarct on cerebral MRI
  2. Minimum of two episodes of acute chest syndrome.
  3. Recurrent painful events (at least 3 in the 2 years prior to enrollment).
  4. Abnormal TCD study requiring starting on chronic transfusion therapy.
  5. At least one silent infarct lesion on a MRI scan of the head.

• A familial haploidentical donor without homozygous sickle cell disease

• Adequate organ function (renal, liver, cardiac and pulmonary function)

• Karnofsky or Lansky (age appropriate) Performance Score ≥50%

• Liver biopsy is optional to assess for iron overload in chronically transfused patients.

Exclusion Criteria:

• Females who are pregnant or breast-feeding
• SCD Patients with documented uncontrolled infection
• SCD patients who have an unaffected HLA matched family donor willing to proceed to donation
• Karnofsky/Lansky (age appropriate) Performance Score <50% (hemiplegia alone secondary to a previous stroke is not an exclusion)
• Demonstrated lack of compliance with medical care.
• Clinically significant fibrosis or cirrhosis of the liver
• Previously received a HSCT