1. Tolerance Induction Dr. S. Strober Stanford University

2. Holy Grails Graft Anti- Tumor Activity without Graft vs Host Disease after Bone Marrow Transplantation for Leukemia/Lymphoma Organ Transplant Acceptance without Mainteneance Immunosuppressive Drugs(Immune Tolerance)

3. Total Lymphoid Irradiation Treatment for Hodgkin’s Disease Safe and effective (10,000 patients ) Multiple small doses of irradiation Targeted to lymph nodes, spleen, and thymus-other tissues shielded Outpatient procedure

4. Non-Myeloablative TLI/ATS Protocol ATS i.p. Injections D-24 D-12 D-10 D-8 D-1 D0 Donor: C57BL/6 (H2b) Bone marrow + or - Spleen or blood T cells Recipient: BALB/c Total Lymphoid Irradiation:17 Doses (240 cGy/dose) *Figure by A. Pillai MD

5. TLI + ATG Treated Mice are Resistant to GVHD Lan F. et al., J. Immunol. 167, 2001

6. TLI/ATG Conditioning for Hematolymphoid Malignancies Using MRD/URD ATG 1.5 mg/kg/day Day 0 GVHD prophylaxis Day 180 Days -11 to -7 CSA MMF TLI 800 cGy over 10 fractions Days -4 to -1Days -11 to -7 Infection Prophylaxis HSV: if +ve acyclovir 400 mg BID CMV: blood PCR weekly EBV: blood PCR every 2 weeks PCP: Septra DS BID weekends D+42 Fungus: if prior infection or URD Lowsky R, et al., NEJM Sept 2005

7. Sykes and Spitzer, Nat. Med.11,1164: 2005

8. Non-Myeloablative Post-Transplant Conditioning And Bone Marrow Cell Infusion Non-Myeloablative Post-Transplant Conditioning And Bone Marrow Cell Infusion ATG i.p. Injections D0 D1 D2 D4 D6 D8 D14 D15 Donor (C57BL/6) Bone marrow cell infusion (50 x 10 6 ) Heterotopic Heart TX Donor: C57BL/6 (neonatal) Recipient: BALB/c Total Lymphoid Irradiation:10 Doses (240 cGy/dose)

9. Heterotopic Heart Graft Survival Organ Donor: CD1d-/- (BALB/c background) or WT BALB/c Recipient: C57BL/6 BM Donor: CD1d-/- (BALB/c background) Or WT BALB/c