Delayed Blood Stem Transplantation in HLA Matched Kidney Transplant Recipients to Eliminate Immunosuppressive Drugs.

This is a single-center, open-label study in adult renal transplant patients.Twenty five
patients with functioning HLA matched living donor kidney transplants will receive TLI, rATG
and an infusion of cluster of differentiation (CD)34+ (Stem/Progenitor cells) selected
granulocyte colony-stimulating factor (G-CSF) mobilized blood cells combined with CD3+ T
cells (Stem/ Progenitor cells) from their transplant donors.Transplant recipients will have
their maintenance Immunosuppressive drugs adjusted for four weeks before starting the TLI and
ATG conditioning regimen. Mycophenolate Mofetil (MMF) will be maintained at 0.5 gm twice a
day per day during this four week period during TLI and ATG treatments, and increased to 1
gram twice a day immediately after the completion of TLI at day 14.

MMF will be tapered starting 6 (six) months later. Tacrolimus levels will be targeted to
blood trough levels of 4-6 ng/ml in the month before the start of the conditioning regimen.
This target would be increased to 8-10 ng/ml at the start of the TLI and ATG conditioning
regimen. At serial time points (1) graft function will be monitored. (2) chimerism will be
measured in recipient white blood cell subsets, (3) protocol biopsies of the graft will be
obtained. An attempt will be made to discontinue Tacrolimus at 12 months if (1) chimerism is
detectable for least 180 days after the CD34+ and CD3+ cell infusion, (2) there is no Graft
Versus Host Disease (GVHD), (3) there is stable graft function without clinical rejection
episodes and (4) lack of histological rejection on protocol biopsies.

Recipients will be given the target dose of ≥ 8 x 10^6 CD 34 + cells/Kg and a dose of 5x10^6
CD3+ cells/Kg.The dose would be sequentially increased to 10, 15 and 25 x 10^6 CD3+ cells/Kg
if fewer than 4 of 5 consecutive patients achieve whole blood chimerism of ≥ 30 % at 60 days.
If 4 of 5 patients achieve this level of chimerism, then all subsequent enrolled patients
will receive this dose.

Inclusion Criteria:

1. All consenting adults of age 18 years and older with previous HLA matched sibling
living donor renal transplants who still have their HLA- matched kidney donor
available, and who have no history of acute or chronic rejection.

2. Patients who agree to participate in the study and sign an Informed Consent

3. The HLA-matched donor meets the Stanford Bone Marrow Transplant criteria for stem cell
donation, agrees to participate and has signed an Informed Consent.

4. The pair is confirmed to be HLA-matched (2 haplo type match) as determined by the
histocompatibility laboratory at Stanford.

5. Patients who have no known contraindication to the administration of rabbit ATG or
radiation

6. Males and females of reproductive potential who agree to practice a reliable form of
contraception for at least 18 months post transplant.

Exclusion Criteria:

1. Known allergy to ATG or a known allergy to rabbit proteins.

2. History of malignancy with the exception of non-melanoma skin malignancies.

3. Pregnant women or nursing mothers.

4. Serological evidence of HIV, Hepatitis B (HepBsAg+) or Hepatitis C infection.

5. Leukopenia (with a white blood cell count < 3000/mm3) or thrombocytopenia (platelet
count < 100,000/mm3)

6. Previous history of acute or chronic rejection of the kidney transplant or recurrence
of the original disease.

7. Screening kidney biopsy demonstrating acute or chronic rejection, recurrence of
original disease or interstitial fibrosis/Tubular Atrophy (IF/TA) score greater than
1.