Tolerance: It's in your blood

摘要

Intentional immunologic tolerance in solid organ transplantation has finally come of age. In pioneering studies published previously by Spitzer et al, multiple myeloma patients with ESRD received nonmyeloablative conditioning followed by combined bone marrow and kidney transplant from an HLA identical living donor. The objective was a mixed-chimerism pathway to tolerance based on approaches that had been highly successful in small and large animal studies. Even though 4 out of 6 patients promptly lost chimerism, renal allografts have survived in those patients for as long as 8 years off all immunosup-pression. In provocative follow up studies just published in the New England Journal of Medicine, the approach was extended to recipients without myeloma who had only 1 haplotype matched donors. Despite the greater degree of histoincompatibility, 4 of 5 patients continue to have excellent graft function 1 to 4 years after withdrawal of all immunosuppression. These studies represent an unquestioned leap forward for the field. Ideally, such protocols would ultimately involve non-toxic conditioning regimens and entirely avoid the risk of GVHD inherent in bone marrow transplantation, which was seen in some of the patients in the first series. In addition, the requirement for weeks of pretransplant treatment limits its utility in cadaveric transplantation. Such concerns motivate the search for alternative approaches to achieving tolerance though mixed chimerism.