T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias

CD3/CD19 depletion of mismatched donor grafts in the setting of reduced intensity, immune-ablative conditioning for patients with sickle cell disease and other transfusion-dependent anemias should sufficiently achieve engraftment while decreasing the incidence of treatment-related toxicities and achieving an acceptable incidence of graft versus host disease. Utilizing mismatched unrelated volunteer donors and haploidentical related donors will increase the number of patients able to undergo hematopoietic stem cell transplant (HSCT) for these diseases. Additionally, the institutional availability of virus-specific, donor-derived cytotoxic T lymphocytes should address complicated viral infections refractory to standard anti-viral therapy.

The purpose is to:

* To provide alternate donor transplantation from cryopreserved stem cell grafts that are fully characterized for safety and potency to patients with severe sickle cell disease, beta-thalassemia major, or Diamond-Blackfan anemia who do not have matched sibling donor, matched unrelated donor or cord blood donor options.
* To utilize a reduced-intensity conditioning regimen to achieve minimal treatment-related morbidity and mortality while attaining sustained donor engraftment and donor chimerism \>20% in order to rescue disease phenotype, specifically in SCD patients.
* To utilize ex-vivo T-cell depletion methods to prevent graft-versus-host disease in the setting of mismatched donor transplantation.
* To utilize additional donor cell products to ensure sufficient immune reconstitution in the immediate post-transplant period, to improve mixed chimerism or provide non-specific anti-viral activity in patients with virus reactivation in the post-transplant period.
* To utilize calcineurin inhibitor-free regimen in an effort to minimize/prevent central nervous system toxicity