The aim of this study to evaluate the safety and efficacy of a nonmyeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with sickle cell disease (SCD) who have a matched related major ABO-incompatible donor. The nonmyeloablative regimen will use alemtuzumab, total body irradiation (TBI) and sirolimus for immune suppression. This study will expand the access of HSCT for patients with SCD who are currently not eligible because of donor restrictions.
Patients must be ≥ 12 months and < 19 years of age at the time of study enrollment.
homozygous Hb S disease (HbSS),
sickle-Hb C disease (HbSC),
sickle beta-plus-thalassemia (HbS/β+), or
Patients who are unable to comply with or follow the study protocol.
Patients with known hypersensitivity to sirolimus, its derivatives or to any of its components.
Single group
Alemtuzumab
DrugAlemtuzumab, Day -7 to -3. Dose: 0.2mg/kg/dose SC once daily x 5 days
Total Body Irradiation
RadiationTBI 300 cGy on Day -2
Sirolimus
DrugSirolimus is used for GVHD prophylaxis
Incidence of pure red cell aplasia (PRCA)
Clinical definition: reticulocytopenia \< 10x109/L (\< 1%) lasting more than 60 days after HSCT, or Pathological definition: the absence of erythroid precursors in the marrow in the setting of adequate myeloid, lymphoid and megakaryocytic precursors
RBC chimerism measured by peripheral blood flow cytometry
Peripheral blood for RBC chimerism on flow sorted erythroid precursor cells
RBC chimerism measured by bone marrow BFU-erythroid forming colonies
Bone marrow will be performed between Day +45 and +60
Primary graft failure
Measured by donor chimerism from peripheral blood and bone marrow
Secondary graft failure
Measured by donor chimerism in peripheral blood and bone marrow
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