Expanded Access Protocol Using Alpha/Beta T and CD19+ Depleted PBSC

Only 25-30% of patients who may benefit from HSCT have a matched related donor. An unrelated
cord blood may not be available due to size or matching criteria, or if a reduced intensity
regiment is recommended. The risk of severe graft vs. host disease (GVHD) and other
complications is higher with unrelated donors, or partially matched related donors. At the
Children's Hospital of Philadelphia (CHOP) there is extensive experience using mismatched
unrelated donors or partially matched related donors with complete or partial T depletion to
reduce the risk of severe GVHD.

PATIENT AND DONOR ELIGIBILITY

Patients who lack an HLA matched sibling and who are candidates for allogeneic
hematopoietic stem cell transplant (HSCT) but do not meet criteria for current open
institutional protocols using ClinMACs device for β T/CD19+ depletion.

Patients with the following transplantable diseases:

Non-malignant diseases:

- Metabolic storage diseases correctable by HSCT

- Bone marrow failure syndromes

- Immunodeficiencies/immune dysregulation syndromes

- Sickle cell disease with severe central nervous system (CNS) vasculopathy

- Other hemoglobinopathies requiring HSCT

Malignant diseases:

- Acute leukemias

- Chronic leukemias

- Lymphomas

- Myelodyplastic syndrome

Organ function criteria:

It is important to note that the conditioning prescribed to the patient will be determined
based on the disease and organ status and will be regimens considered standard. Appropriate
combinations of chemotherapy, immunotherapy and/or radiation will be determined on an
individual basis.

Patient eligibility will be assessed as per our institutional standard operating
procedures:

- Lansky or Karnofsky performance >60

- Renal function: will be determined based on serum creatinine as per our Institutional
SOP

- Hepatic: Transaminases will be assessed as per current institutional SOP

- Cardiac shortening fraction >27% as per institutional SOP

- Bilirubin <2.5x normal (unless elevation due to Gilberts disease) as per Institutional
SOP

- No active untreated infection

- Signed informed consent

- No fully HLA matched sibling donor available.

- Females of childbearing potential must have negative pregnancy test.

Donor Eligibility Patients must have an identified living donor

- Donor selection will comply with 21 Code of Federal Regulations (CFR) 1271*

- Unrelated donor that meets the matching criteria of the NMDP: Unrelated donors that
may be up to a one antigen mismatch at A, B or DRB1. donor

- Related donor mismatched at one to five antigens (haploidentical)

- Donor suitable for mobilization of peripheral stem cells and apheresis and fulfills
infectious disease criteria as per our institutional SOP, including HIV, Hepatitis B
(HepB), Hepatitis C (HepC) polymerase chain reaction (PCR) negative.

- CHOP bone marrow transplant (BMT) procedures apply for determining donor eligibility,
including donor screening and testing for relevant communicable disease agents and
diseases. Our donor collection program is Foundation for the Accreditation of Cellular
Therapy (FACT) accredited.

- Unrelated donor identified through the National Marrow Donor Program (NMDP) and
fulfills the NMDP criteria for donation. Unrelated donor willing and able to undergo
mobilization of peripheral stem cells and apheresis

- The donors selected for this investigational new drug (IND) will either be unrelated
donors identified through the National Marrow Donor Program (NMDP) or related donors.
Regarding the unrelated donors; NMDP procedures for determining donor eligibility
include donor screening and testing for relevant communicable disease agents and
diseases.

Exclusion criteria:

- Uncontrolled bacterial, viral or fungal infections

- Fully HLA matched sibling donor

- Donor unable to donate peripheral stem cells

- Pregnant Females