Delayed Tolerance Through Mixed Chimerism

Description

Recipients of previous living donor (LD) or deceased donor (DD) kidney transplants that were maintained on conventional immunosuppression (I.S.), will receive a conditioning regimen that includes rituximab on study day -6, fludarabine 15 mg/m2/day on days -5 to -3 (3 doses), Cyclophosphamide (30 mg/kg/day) on days -5 and -4, followed by local thymic irradiation (7 Gy) on day -1 and Siplizumab (anti-CD2 mAb) on days, -2, -1, 0 and +1. Donor hematopoetic stem cells (HSCs) will be infused on study day 0. Methylprednisolone 250mg/day will be started on day 0 and tapered off by day 20 (Fig. 2). Prophylaxis will be provided for hemorrhagic cystitis, PCP, fungal infection, CMV, and perioperative infection. All patients who require any blood transfusion will receive only leukocyte-depleted and irradiated blood products for a period of at least 12 months following HSC Transplant. The recipients will undergo renal allograft biopsy at 6 months after HSCT. If the I.S. withdrawal criteria are met, I.S. will be slowly tapered off by 9-12 months