Poster Board III-256
Specific tolerance following combined kidney and bone marrow transplantation (Kd/BMT)for patients with end stage renal disease (ESRD) with or without an underlying malignancy has been accomplished, as evidenced by prolonged normal renal function without ongoing immunosuppression (IS)and the demonstration of in vitro donor specific hyporesponsiveness (N Engl J Med 2008; 358:353-361; Am J Transplant 2006;6:2121-2133). In order to achieve potent anti-myeloma responses and induce tolerance through the induction of mixed chimerism (MC) for the renal allograft, 7 patients (median age 48 (34-55) yrs with multiple myeloma (MM) and ESRD received a combined HLA-matched Kd/BMT, with longest follow-up time of almost 11 years. An eighth pt developed cyclophosphamide (CY) cardiotoxicity on day -5 and did not receive a transplant. Preparative therapy for the transplants consisted of CY 60 mg/kg (days -5, -4) with hemodialysis 14 hrs after each CY dose, equine anti-thymocyte globulin, 15-20 mg/kg on days -1, +1, +3, and +5 and thymic irradiation (700 cGy) on day -1. Cyclosporine (CSP) was begun on day -1, with combined Kd/BMT on day 0. Nine additional donor lymphocyte infusions were given to 5 pts (5 for chimerism conversion, 4 for persistent/progressive disease (PD)). Acute (A) and chronic (C) GVHD developed in one patient following DLI for early PD, while chronic GVHD developed in two pts (one after a second stem cell transplant). Characteristics and outcomes of the 7 combined Kd/BMT recipients are as follows:
# after 2nd transplant (myeloablative) from the same donor ; FDC: full donor chimerism In summary, 5 of 7 pts are alive, 4 without evidence of MM from 2.7 to 10.9 yrs post-Kd /BMT. Three pts have normal renal function without IS, while two pts have normal renal function on IS for chronic GVHD. Sustained renal allograft tolerance and prolonged anti-myeloma responses are achievable following nonmyeloablative HLA-matched kidney and BMT and the induction of mixed chimerism. This study was supported by the Immune Tolerance Network, National Institute of Allergy and Infectious Diseases.
Off Label Use: Equine anti-thymocyte globulin: in vivo T cell depletion Cyclophosphamide:conditioning therapy for transplantation.
Asterisk with author names denotes non-ASH members.