Tolerance Induction after Kidney Transplantation Stephan Busque MD M Sc FRCSC Director, Adult Kidney and Pancreas Transplantation Program Stanford University

Stanford Kidney Transplant Program (n=726)

Immunosuppression Medication Side-effects Infection Cancer Diabetes Cosmetic NEPHROTOXICITY

HLA-matched Combined Kidney/Hematopoietic Cell Transplantation Protocol Donor CD34+ cell infusion Inclusion of CD3+ cells (dose 1 x 10 6 /kg) Withdraw immunosuppression if: -stable macrochimerism -no evidence of rejection -no GVHD rATG (1.5 mg/kg) Kidney Transplant Day 0 TLI Cyclosporine wean month 3-6 Prednisone x 10 days only MMF d/c day 30

12/06 Subject Characteristics Patient # Age/ Gender ESRD cause HLA match Relation to donor CD34 + dose (x10 6 /kg) CD3 + dose (x10 4 /kg) 1 48 M?6brother FFSGS6sister M dysplasia 6brother

12/06 Chimerism Subject # 1

Days After Transplantation C S A mg/day Drug Taper

12/06 Allograft Function Subject # 1 Immunosuppression stopped

12/06 Chimerism Subject # 2

12/06 Allograft Function Subject # 2

12/06 Chimerism Subject # 3

12/06 Allograft Function Subject # 3

12/06 Clinical Outcome – Current Status Patient # F/U Serum creatinine (mg/dL) ImmunoRx Chronic rejection/ # biopsy 1 21 mo1.4 Stopped at 6 mo 0/ mo1.2 CsA (81 ng/mL, C 0 ) MMF 0/1 3 8 mo1.2 CsA (359 ng/mL, C 2 ) 0/1

Tolerance project: New directions Increase dose of radiation from 100 to 120 cG Increasing T-cell dose and/or CD 34 Expand to: –Non matched donor-recipient pair –Liver transplantation