Mixed chimerism improves long-term kidney transplant outlook

Mixed chimerism – the continued mixing of donor and recipient blood cells following a transplant of blood progenitor cells – could improve outcomes for kidney transplant recipients, according to a new clinical study in about 50 patients. The results suggest persistent mixed chimerism achieves this effect by reducing the need for risky immunosuppressive drug regimens. Transplant recipients typically depend on immunosuppressive drugs to combat organ rejection, graft-versus-host disease and other immune complications. But these drugs present a host of side effects, including toxicity and increased risk of infection, cancer, diabetes, hypertension and other conditions. Building on prior work in animal models as well as preclinical and clinical studies, Stephan Busque and colleagues set out to test whether establishing persistent mixed chimerism – defined as a donor origin for at least 1% of circulating blood cells – could confer immune tolerance for an organ graft from the same donor. In a cohort of 29 patients who received kidney and blood progenitor cell transplants from fully immunologically matched donors, 24 patients achieved complete withdrawal from immunosuppressive drugs, with no rejection episodes, for at least two years. Several of these patients survived and retained their donated kidneys for more than eight years. Results were less robust in another cohort of 22 patients who were only partially immunologically matched to their donors. In this group, 10 patients were able to substantially reduce – but not eliminate – their dependence on immunosuppressive drugs.

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