Presented at:
2007 American Transplant Congress
San Francisco, CA, May 5-9, 2007
The Long-Term Evaluation of HLA-Mismatched Combined Kidney and Bone Marrow Transplant Recipients after Complete Withdrawal of Immunosuppression
Kawai T, Sachs DH, Spitzer T, Tolkoff-Rubin N, Saidman S, Williams W, Dey B, Goes N, Ko D, Wong W, Colvin RB, Sykes M, Cosimi AB
Transplantation Unit, Massachusetts General Hospital, Boston, MA; Trasnplant Biology Research Center, MGH, Charlestown, MA; Bone Marrow Transplant Unit, MGH, Boston, MA; Pathology, MGH, Boston, MA; this Study was Performed in Partnership with Immune Tolerance Network
BACKGROUND: Induction of allograft tolerance has been the ultimate goal in organ transplantation.
METHODS: Five subjects with ESRD received combined kidney and bone marrow transplantation (CKBMT) from HLA mismatched donors. The preparative regimen consisted of cyclophosphamide, thymic irradiation, anti-CD2 mAb and a 9-14 months course of a calcineurin inhibitor. Two subjects also received two doses of anti-CD20 mAb prior to transplant.
RESULTS: All recipients developed transient mixed chimerism without GVHD.Complete withdrawal of immunosuppressive medication was achieved in 4/5 recipients with current immunosuppression-free survival exceeding 3.2, 2.5, 1.1 and 0.2 years. A recipient rejected his kidney allograft on day 10. (1) The most recent creatinine/GFR of these 4 subjects were 1.2/61, 1.6/75, 1.6/96 (by renogram), 1.8/71 ml/min, respectively. (2)Although Subjects 2 and 5 initially developed anti-donor antibodies (ADA), both recipients lost ADA by 10th and 3rd month, respectively. Subject 4 developed post-transplant de novo anti-class II ADA one month after discontinuation of his immunosuppression, but without any functional derangements. (3) Subjects 1, 2 and 4 showed donor specific hyporesponsiveness in CML and MLR after nine months. (4) Allograft biopsies taken at 3 years from Subjects 1 and 2 revealed normal glomerulus, no tubulitis and no vasculopathy by light and electron microscopic examination with no C4d staining. Biopsy taken at 1.5 years from Subject 4 showed positive C4d deposition with no changes diagnostic of rejection. A most recent biopsy taken from Subject 5 on day 243 showed no rejection. (5) In Subject 1, extensive warts due to human polyoma virus existed before transplantation, but it disappeared after discontinuation of immunosuppression. All four patients show no hypertension, no DM, no abnormal lipid profiles.
CONCLUSIONS: Renal allograft function of CKBMT recipients has been stable up to 3 years after complete withdrawal of their immunosuppression.