Standardization of CD3+ T Cell Dose for Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplantation From Matched Related Donors

The optimal CD3+ cell dose to be used for allo HSCT is unknown. In addition, there are
multiple variables in addition to CD3+ cell dose which affect engraftment, immune
reconstitution, GVH and GVL in these patients including recipient age, diagnosis, disease
status at transplantation, donor/recipient tissue type match, preparative regimen, and GVHD
prophylaxis. Thus the ability to produce products with a fixed CD3+ content is critical to
further research and ultimately to the definition of the "right dose" of CD3+ cells for
various clinical situations.

Patients who meet eligibility criteria will receive a peripheral blood stem cell product from
their original matched sibling donor engineered to deliver a dose of 3.0+/-0.5 x107 CD3+
cells/kg recipient body weight. Other components of the graft will not be manipulated and the
recipient will receive the total number of cells collected with the exception of minimal
losses that occur during the process of CD3+ T cell isolation.

Inclusion Criteria:

1. Patients must be ≥19 years of age.

2. Patients must meet all the UAB diagnosis and disease status criteria for clinical
appropriateness for myeloablative allo HSCT derived from ASBMT and NCCN guidelines.

3. Patients must have a 10/10 HLA matched sibling (excluding identical twin). All donors
will be evaluated for eligibility and suitability per standard of care according FACT
and NMDP guidelines.

4. Adequate organ function: All organ function testing should be done within 28 days of
study registration.

5. Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated
Acquisition) scan or echocardiogram.

6. Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity)
≥ 50% predicted, DLCO (alveolar diffusion capacity for carbon monoxide) (corrected for
hemoglobin) ≥ 50% of predicted.

7. Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60
mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula

8. Performance status: Karnofsky ≥ 70%

9. Hepatic (values to be less than what is considered grade II toxicity per the CTCAE
(common terminology criteria for adverse events)

Exclusion criteria

1. Uncontrolled infections, defined as positive blood cultures within 72 hours of study
entry, or evidence of progressive infection by imaging studies such as chest CT scan
within 14 days of registration.

2. HIV positive patients.

3. Prior autologous or allogeneic transplantation for any disease.

4. Scheduled to receive non-myeloablative or reduced intensity conditioning regimen.

5. High Risk Features associated with increased relapse risk or poor outcomes:

1. AML/ALL: with Bi-phenotypic features

2. AML: Refractory to Induction and salvage therapy

3. ALL: Refractory to Induction and salvage therapy

4. CML: Active blast crisis

5. HL: Disease refractory to chemotherapy or targeted therapy

6. NHL: Disease refractory to chemotherapy or targeted therapy