We have achieved successful induction of long-term immunosuppression (IS) free renal allograft survival in HLA mismatched kidney transplantation using cyclophosphamide (CP) based conditioning and combined kidney and donor bone marrow transplantation. Transient mixed chimerism (MC) for up to 3 weeks was induced in all recipients. IS was successfully discontinued in 7/10 recipients for more than 5 years. Four of them remain off IS and continue with normal kidney function after more than 8 to 14 years. Wider clinical application has been hampered by acute kidney injury (AKI) shortly after transplantation in 9/10 recipients. We therefore conducted a pilot study, in which cyclophosphamide was replaced with low-dose (1.5 Gy X 2) TBI. The first two recipients did well without development of AKI. One recipient successfully discontinued his IS at one year and remains well without ongoing IS for 3 years. Because sufficient chimerism was not detected, low dose IS has been continued in the second recipient. A third TBI recipient received belatacept/ATG in place of anti-CD2 mAb. Transient MC without AKI was observed and he is currently doing well with low dose MMF only to control IgA recurrence. Conclusion: MC and long-term IS free renal allograft survival were achieved without AKI with low dose TBI-based regimens.

CITATION INFORMATION: Kawai T., Spitzer T., Oura T., Torkoff-Rubin N., Elias N., Sykes M., Colvin R., Sachs D., Cosimi A. Non-Myeloablative Conditioning with Low-Dose Total Body Irradiation in Place of Cyclophosphamide Induces Mixed Chimerism and Long-Term Immunosuppression Free Allograft Survival without Acute Kidney Injury in HLA Mismatched Kidney Transplantation Am J Transplant. 2017;17 (suppl 3).

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