Expanded Access to T-cell Depleted Haplo-Identical Stem Cells for Patients Receiving Haplo-Identical and Unrelated Cord Blood Transplants

The primary purpose of the study is to provide expanded access of T-cell depleted
haplo-identical stem cells for patients receiving allogeneic transplantation from a related
haplo-identical donor and an unrelated, umbilical cord blood (UUCB) unit(s) for the treatment
of high risk malignancies and non-malignant disorders. The T-cell depleted haplo-identical
stems cells are intended to facilitate early, short-term myeloid engraftment with the primary
goal of minimizing early infections and other non-relapse mortality while the UUCB cells
engraft as the durable and permanent graft. Patients with high risk or refractory
malignancies, or non-malignant disorders amenable to stem cell transplantation therapy but
lacking conventional related or unrelated donors will be eligible for this protocol.

Inclusion Criteria:

- Have a consenting related haplo-identical (3/6, 4/6, or 5/6 if DRB1 mismatch) stem
cell donor.

- Have one or two available 4, 5, or 6/6 antigen matching unrelated UCB unit(s) that
will deliver a total cell dose >3.0 x 10e7 cells/kg. Patients who do not have a single
UCB unit that will deliver the minimum required cell dose, two partially HLA-matched
UCB units which together meet the minimum cell dose requirement, can be used for 1
transplant. These units must be HLA-matched minimally at 4 of 6 HLA-A and B (at
intermediate resolution by molecular typing) and DRB1 (at high resolution by molecular
typing) loci with the patient, and HLA-matched at 3 of 6 HLA- A, B, DRB1 loci with
each other (using same resolution of HLA typing as indicated above). There is no
limitation on maximum cell dose.

- Have a high risk or refractory malignancy, or non-malignant disorder amenable to stem
cell transplantation therapy.

- Meet eligibility requirements for allogeneic transplant per institutional standard
practices.

- Have given written informed consent according to FDA guidelines (or consent of
parent/legal guardian as applicable).

- Be <65 years of age at the time of study enrollment.

Exclusion Criteria:

- Have a consenting 8/8 or 10/10 allele matched, consenting, related or unrelated
hematopoietic stem cell transplant (HSCT) donor.

- Have a life expectancy of less than 3 months.

- Have uncontrolled infections at time of cytoreduction.