A Pilot Study of HSCT for Patients With High-risk Hemoglobinopathy Using a Nonmyeloablative Preparative Regimen

This is an interventional treatment trial for Sickle Cell Disease focused on measuring Sickle Cell Disease, Thalassemia, Hemoglobinopathies Read More

Inclusion Criteria:

• Patients with SCD 0-35 years of age with an HLA-identical or 1 HLA antigen mismatched bone marrow or up to 2 HLA antigen mismatched umbilical cord blood (UCB) donor with one or more of the following:

  • Stroke, CNS hemorrhage or a neurologic event lasting longer than 24 hours, or abnormal cerebral MRI or cerebral arteriogram or MRI angiographic study and impaired neuropsychological testing,
  • Acute chest syndrome with a history of recurrent hospitalizations or exchange transfusions,
  • Recurrent vaso-occlusive pain 3 or more episodes per year for 3 years or more years or recurrent priapism,
  • Impaired neuropsychological function and abnormal cerebral MRI scan,
  • Stage I or II sickle lung disease,
  • Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate [GFR] 30-50% of the predicted normal value),
  • Bilateral proliferative retinopathy and major visual impairment in at least one eye,
  • Osteonecrosis of multiple joints with documented destructive changes,
  • Requirement for chronic transfusions but with RBC alloimmunization >2 antibodies during long term transfusion therapy.
  • Patients with transfusion dependent Thalassemia 0-35 years of age with an HLA-identical or 1 HLA antigen mismatched bone marrow or up to 2 HLA antigen mismatched UCB donor.

• Second Transplants

  • Patients with sickle cell disease or Thalassemia who have failed to engraft or have autologous recovery are eligible for this protocol.
  • Patients must meet above criteria.
  • If first transplant was a non-myeloablative regimen, the second transplant can occur at any time.
  • If the first transplant was a myeloablative regimen, then the second transplant must be > 6 months from the first transplant.

Exclusion Criteria:

• Patients with one or more of the following:

  • Karnofsky or Lansky performance score <70,
  • Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy,
  • Stage III-IV lung disease,
  • GFR<30% predicted normal values.
  • Pregnant or lactating females.
• Active serious infection whereby patient has been on intravenous antibiotics for one week prior to study entry. Any patient with AIDS or ARC or HIV seropositivity. Any patient with invasive aspergillums infection within one year of study entry.
• Psychologically incapable of undergoing BMT with associated strict isolation or documented history of medical non-compliance.
• Patients not able to receive TLI due to prior radiation therapy.

Donor Inclusion Criteria

• Donor must be in good health based on review of systems and results of physical examination.
• Donor must have a normal hemoglobin, white count, platelet count and PTT.
• Female donors of childbearing potential must have a negative pregnancy test.

Donor Exclusion Criteria

• Donor has active infection (including HIV, hepatitis).
• Donor is a lactating female.

Donor Selection

In the case where more than one donor meets the eligibility criteria, donor selection will be guided by the following considerations:

• HLA A, B, DRB1 identical sibling donor is preferable to an unrelated donor
• Homozygous normal donor is preferable to heterozygote (carrier)
• ABO-compatible donor is preferable to ABO-incompatible donor
• Younger donor is preferable to older
• Cytomegalovirus seronegative donor is preferable to CMV seropositive donor, if the patient is CMV negative