Background: We report the long-term results (up to 10 years) of one-haplotype HLA mismatched kidney transplantation without maintenance immunosuppression (IS) following combined kidney and bone marrow transplantation (CKBMT).
METHODS: The first three subjects underwent CKBMT after a nonmyeloablative conditioning regimen (NKD03) including cyclophosphamide, thymic irradiation, anti-CD2 mAb. Two subsequent subjects received a modified regimen with 2 doses of pretransplant rituximab (mod NKD03). The five most recent subjects received a revised regimen (ITN036), in which four doses of peri-transplant rituximab were administered.
RESULTS: All 10 subjects developed transient chimerism becoming undetectable by day 21 without GVHD. IS was discontinued in 8 subjects 8-14 months post-transplant. One developed acute rejection 2 months later and has remained on chronic IS. The remaining seven subjects have been off IS with stable renal function for periods of 3.4-10.3 years. One subject in NKD03 developed recurrent glomerulonephritis and has therefore been treated with MMF since the 7th year. Two subjects treated with mod NKD03 developed donor specific antibody (DSA) after IS withdrawal and early chronic rejection is now suspected after 6 and 7 years. In both of these subjects, insufficient CD19+ cell depletion with high serum BAFF levels (5-13 ng/ml) was observed during the first 6 months. In ITN-036 subjects, CD19+ cell were almost completely depleted from peripheral circulation for 6 months after CKBMT and DSA has not been detected in any of these recipients.
CONCLUSIONS: Long-term stable tolerance appears inducible despite induction of only transient chimerism via CKBMT. Our observations suggest that incomplete B cell depletion may increase the risk of DSA development because of high BAFF induced by B cell depletion and that DSA development can be prevented by more intensified B cell depletion during the first 6 months.
To cite this abstract in AMA style:Kawai T, Sachs D, Sprangers B, Spitzer T, Tolkoff-Rubin N, Saidman S, Zorn E, Williams W, Smith R, Colvin R, Sykes M, Cosimi A. Nonmyeloablative Conditioning Regimen with B Cell Depletion and Long-Term Outcome of HLA Mismatched Combined Kidney and Bone Marrow Transplantation without Maintenance Immunosuppression [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/nonmyeloablative-conditioning-regimen-with-b-cell-depletion-and-long-term-outcome-of-hla-mismatched-combined-kidney-and-bone-marrow-transplantation-without-maintenance-immunosuppression/. Accessed December 2, 2020.
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