• To evaluate the risk of graft loss and severe GVHD or transplant related mortality at < 100 days following HLA-mismatched non-myeloablative stem cell transplantation. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  

• To evaluate progression free and overall survival following HLA mismatched non-myeloablative stem cell transplantation for hematologic malignancy. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  

Drug: MEDI-507
MEDI-507 0.1 mg/kg on transplant day-8, 0.6 mg/kg on days-7 and -6
Procedure: Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant
Cyclophosphamide 60 mg/kg on transplant days -7 and -6; Fludarabine 25 mg/m2 days -5,-4,-3,-2,-1; MEDI-507 0.1 mg/kg on day -8, 0.6 mg/kg on days -7,-6

One major obstacle to further advancement in the role of bone marrow transplant (BMT) in hematological malignancies is graft-versus-host-disease (GVHD), which can best be prevented by removing T-cells from the donor stem cell product. However, previous experience with T-cell depletion has been associated with an increased rate of engraftment failure and leukemic relapse. Another obstacle is that a large fraction of leukemia and lymphomas afflict older patients who are more prone to GVHD and have co-morbid conditions that prevent them from being a candidate for BMT.

This trial uses a non-myeloablative conditioning regimen with cyclophosphamide, MEDI-507, fludarabine, and thymic irradiation followed by a T-cell depleted PBSC infusion. Cyclosporine is used for GVHD prophylaxis, and tapered beginning on day 35. Data from our mouse model and previous clinical trials have demonstrated that this approach can induce mixed chimerism without GVHD, with the potential for conversion of mixed chimerism to full donor hematopoiesis following donor leukocyte infusions.