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Macrochimerism and clinical transplant tolerance.

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Achieving macrochimerism through combined kidney and hematopoietic cell transplantation is key for transplant tolerance. The Stanford protocol shows promise in both HLA-matched and mismatched kidney transplants, enabling drug cessation.

Keywords:
ChimerismHematopoietic cell transplantationImmune toleranceKidney transplantation

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Area of Science:

  • Immunology
  • Transplantation Medicine
  • Regenerative Medicine

Background:

  • Macrochimerism is theorized as essential for transplant tolerance.
  • Hematopoietic cell transplantation (HCT) from the organ donor is required for macrochimerism.
  • Clinical trials for tolerance induction via combined kidney and HCT have advanced.

Purpose of the Study:

  • To evaluate macrochimerism achievement in clinical tolerance induction strategies.
  • To compare efficacy and safety of different protocols in HLA-matched and mismatched living donor kidney transplantation.
  • To assess the Stanford protocol's effectiveness in inducing transplant tolerance.

Main Methods:

  • Comparison of three major clinical tolerance induction strategies.
  • Utilizing combined kidney and hematopoietic cell transplantation.
  • Monitoring chimerism levels and patient outcomes in HLA-matched and mismatched recipients.

Main Results:

  • The Stanford protocol demonstrated efficacy in HLA-matched kidney transplantation, allowing 80% of participants to stop immunosuppressants.
  • Consistent multi-lineage macrochimerism exceeding one year is achievable with the Stanford protocol in HLA-mismatched cases.
  • The safety profile of the Stanford protocol aligns with conventional transplantation.

Conclusions:

  • The Stanford protocol is effective for inducing tolerance in kidney transplantation.
  • Macrochimerism is achievable and facilitates immunosuppression withdrawal.
  • Further research will test complete immunosuppression cessation in the second post-transplant year for mismatched cases.