Haploidentical Stem Cell Transplant for Patients With Sickle Cell Disease and Prior Stroke or Abnormal Transcranial Ultrasound
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      Sickle cell disease is a life-long blood condition that can cause damage to the brain and
      other organs of the body. Children may develop severe, debilitating clinical states, with
      stroke or abnormal blood flow to the brain. Treatment generally includes chronic blood
      transfusions which may cause iron overload, potentially leading to severe and sometimes fatal
      complications.

      Hematopoietic stem cell transplant using cells obtained from a sibling or an unrelated
      volunteer donor who is a perfect HLA "match" (same tissue type) for the recipient has shown
      to help, and possibly cure, sickle cell disease. Unfortunately, only about 10-20% of sickle
      cell patients have a HLA matched sibling donor, and the likelihood of locating an appropriate
      HLA matched unrelated donor through the various donor registries is limited.

      Stem cells from partially HLA matched family members (also called haploidentical transplant)
      is an option currently being explored for this patient population. This type of transplant
      has been used and found to be successful in some patients, mostly those with cancers of the
      blood. However, there can be significant complications with haploidentical transplant,
      primarily infection, failure of the graft to grow (graft failure), and a disorder called
      graft-versus-host disease. In addition, few patients with sickle cell disease have undergone
      this procedure. Therefore, the risks and benefits of haploidentical transplants for patients
      with sickle cell disorder are not as well established as those using an HLA identical sibling
      or unrelated donor.

      The primary objective of this study is to assess the safety of haploidentical stem cell
      transplantation for children and adolescents with severe sickle cell disease and stroke or
      abnormal transcranial Doppler ultrasound requiring chronic transfusion therapy. The treatment
      plan will be considered safe if there is not excessive toxicity. Toxicity for this protocol
      is defined as graft failure/graft rejection, severe acute GVHD, or regimen related death
      within 100 days after the last cellular product administered.

      Of note, the protocol was closed to accrual in September 2007 as we had met the stopping
      rules related to graft integrity (graft failure and graft rejection). Participants currently
      enrolled continue to be followed per protocol.
    

Detailed description: 
      Secondary objectives for this protocol include the following:

        -  To estimate 1-year overall and event free survival after transplantation. An event is
           defined as toxicity (graft failure, death, grade III/IV acute GHVD), or a sickle-related
           event (stroke, acute chest syndrome, pain crisis).

        -  To obtain preliminary information regarding donor engraftment among different cell
           subsets, including unsorted mononuclear cell, and lymphoid fractions during the first
           year after transplant.

        -  To observe the rate of acute and chronic GVHD during the first year after transplant.

        -  To assess the proportion of research participants who experience poor graft integrity
           and therefore require additional donor stem cells or lymphocytes.

        -  To document the effect of stem cell transplant on the central nervous system as defined
           by radiological imaging and neuropsychological testing.

        -  To investigate immune reconstitution after transplantation
    

Intervention name(s): Hematopoietic Stem Cell Transplantation; CliniMACS; See intervention description
Intervention type(s): Procedure; Device; Drug
Intervention description(s): Allogeneic stem cell transplant Haploidentical stem cell transplant Mismatched family member donor stem cell transplant T cell selection CD34 enrichment; Hydroxyurea and azathioprine were administered for a 3 month period prior to the initiation of the transplant procedure in an effort to help prevent rejection of the donor product. Approximately 10 days prior to the transplant procedure, all participants received the same preparative regimen consisting of Busulfan, cyclophosphamide, low-dose thiotepa, and OKT3. MMF was administered for GVHD prophylaxis. Two separate infusions of donor stem cells were administered with fixed doses of CD3 and CD34 cells. These haploidentical stem cells were processed using the investigational CliniMACS device.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sickle Cell Anemia; Stem Cell Transplantation; Haploidentical stem cell transplant; T cell depletion; CliniMACS device