We recently proposed that the migration from organ allografts of donor leukocytes and their ubiquitous persistence in recipient tissues is the seminal explanation for allograft acceptance, and the first stage in the development of donor specific nonreactivity (tolerance). In a direct extension of this concept, 16 unconditioned patients were infused with donor bone marrow cells on the day of cadaveric renal (n=9), liver (n=6), and heart (n=1) transplantation. The 16 patients who were treated

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... standard FK 506-prednisone immunosuppression included 3 diabetics who also received pancreatic islets and a liver recipient with a positive lymphocytotoxic crossmatch. All 16 have good whole organ function 2.5 to 13 months later and the 3 diabetics have circulating C-peptide. Using flow cytometry and qualitative or quantitative PCR techniques to detect donor HLA alleles and with study of Y chromosomes in 4 female recipients of male organs, persistent multilineage leukocyte chimerism was found in the blood of all recipients except one whose complete HLA match and same sex donor precluded study. Rejection was diagnosed and successfully treated in 9 (56%) of the 16 patients and transient GVHD in 2 (12.5%). Sustained donor specific hyporeactivity as early as 40 days postoperatively was demonstrable with in vitro tests in the majority of recipients.