Transplantation tolerance: from theory to clinic

Area of Science:

• Immunology
• Transplantation Medicine
• Hematology

Background:

• Hematopoietic chimerism, the coexistence of host and donor blood cells, is crucial for transplant tolerance and cancer immunotherapy.
• Current methods for inducing chimerism and tolerance face challenges with immunosuppression and toxicity.

Purpose of the Study:

• To review clinically relevant methods for inducing hematopoietic chimerism and transplantation tolerance.
• To emphasize reduced intensity transplantation conditioning and post-transplantation cyclophosphamide strategies.

Main Methods:

• Focus on reduced intensity transplantation conditioning regimens.
• Highlight the use of high-dose, post-transplantation cyclophosphamide.
• Discuss strategies to prevent graft rejection and graft-versus-host disease (GVHD).

Main Results:

• Reduced intensity regimens facilitate transient donor-host immune cooperation for malignancy eradication without GVHD.
• These regimens have a favorable toxicity profile, expanding their application.
• Hematopoietic chimerism induction enables solid organ transplant tolerance without maintenance immunosuppression.

Conclusions:

• Reduced intensity transplantation and post-transplantation cyclophosphamide are effective strategies for inducing hematopoietic chimerism and transplantation tolerance.
• These approaches offer improved safety and broader applicability for malignant and non-malignant hematologic disorders and solid organ transplantation.