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

Expanded Access Protocol Using TCR Alpha/Beta T Cell/CD19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells

The primary objective of this protocol is to expand access for patients who lack a fully HLA (Human leukocyte antigen) matched sibling donor, and who are candidates for allogeneic hematopoietic stem cell transplant (HSCT). These patients have a serious or immediately life-threatening disease for which HSCT is indicated. These patients are not eligible for other Children's Hospital of Philadelphia Institutional Review Board (IRB) approved protocols that utilize CliniMACs technology for T depletion.

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.

Stem cells will be processed using the CliniMACS device for alpha/beta and CD19+ T cell depletion. Processing of cells using the CliniMACS will occur in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique.

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 or thalassemia Other diseases treated with 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: Cardiac function will be assessed 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. Subjects with graft failure who require a second HSCT will not need to meet eligibility criteria again prior to the second transplant. Graft failure is a medical emergency that requires HSCT 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