The as;o abstract of the same info presented earlier on this thread at
Message 15688345
3137
The Induction of Allograft Tolerance and Anti-Tumor Response Following Combined HLA-Matched Donor Bone Marrow and Renal Transplantation for Multiple Myeloma with End-Stage Renal Disease
Thomas R Spitzer, F Delmonico, N Tolkoff-Rubin, S McAfee, R Sackstein, B Dey, A Kraus, C Colby, S Saidman, D. H. Sachs, M Sykes, A. B. Cosimi, Massachusetts General Hospital, Boston, MA.
The first description of the successful induction of allograft tolerance following non-myeloablative conditioning and HLA-matched donor bone marrow (BM) and kidney transplantation (KTx) for multiple myloma (MM) with end-stage renal disease (ESRD) was recently published (Transplantation 1999; 68: 480-483). The patient received cyclophosphamide (CY) 60 mg/kg on days -5 and -4, equine ATG 15 mg/kg on days -1, +1, +3 and +5 and thymic irradiation 700 cGy on day -1. Hemodialysis was performed prior to CY and 14 hours after each CY dose. Cyclosporine (CSP) was given on day -1 through day +73. Mixed lymphohematopoietic chimerism (MC) by VNTR analysis was initially induced and maintained through day +98. At 26 months, serum creatinine (Scr) is 0.9 mg/dl and there are no detectable urinary k light chains. A cell mediated lympholysis assay at 2 and 5 months showed host anti-donor activity, consistent with allo-sensitization. At 22 months, the host anti-donor response declined, with CTLp frequencies lower than those against third-party, suggesting the gradual development of donor-specific allotolerance. A second pt received the same conditioning and an HLA-matched donor BM and KTx for k light chain MM with ESRD. MC was induced, although at day +53 the % of donor cells in both the CD3+ T-cell and the CD3- cell fractions was £ 10%. CSP was discontinued on day +77. Scr on day +81 is 0.8 mg/dl. There has been a decline in urinary k light chains from 99.8 mg/dl pre-BMT to 9.4 mg/dl on day +81. Sustained allograft tolerance and an anti-myeloma response have occurred in one pt while a second pt has normal renal function following discontinuation of CSP and evidence of an early anti-tumor response. In vitro evidence of delayed donor-specific allotolerance has also been demonstrated. In conclusion, combined HLA matched donor BM and KTx for MM with ESRD following non-myeloablative conditioning is a feasible approach for successfully achieving allotolerance |
