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Tomotherapy Applied Total Lymphoid Irradiation and Allogeneic Hematopoietic Cell Transplantation Generates Mixed
Lisa Forrest1, John Fechner2, Jennifer Post2
1School of Veternary Medicine, University of Wisconsin, Madison, Wisconsin.
Radiation Research
|August 13, 2021
Summary
A novel tomotherapy-based conditioning regimen successfully induced mixed chimerism in rhesus macaques undergoing allogeneic hematopoietic cell transplantation, showing promise for transplant tolerance without graft-versus-host disease.
Area of Science:
- Immunology
- Transplantation Science
- Medical Physics
Background:
- Allogeneic hematopoietic cell (HC) transplantation is a critical therapy.
- Achieving stable chimerism and preventing graft-versus-host disease (GVHD) remain significant challenges.
- Novel conditioning regimens are needed to improve transplant outcomes.
Purpose of the Study:
- To develop and assess a new methodology for inducing immunological chimerism.
- To evaluate a non-myeloablative helical tomotherapy-based total lymphoid irradiation (TomoTLI) conditioning regimen.
- To test the feasibility of this protocol in a rhesus macaque model.
Main Methods:
- A feasibility study was conducted on seven rhesus macaques undergoing HC allo-transplants.
- Two tomotherapy protocols were compared: TomoTLI (n=5) and TomoTLI/total-body irradiation (TBI) (n=2).
- Donor HC infusions were performed between 1-haplotype matched donor/recipient pairs.
Main Results:
- Five out of seven animals achieved mixed chimerism.
- Three animals receiving the TomoTLI protocol alone demonstrated transient mixed chimerism without GVHD.
- Survival times for these animals were 33, 152, and >180 days.
- The addition of belatacept and TBI resulted in total chimerism and fatal GVHD.
Conclusions:
- Non-myeloablative TomoTLI is a feasible conditioning regimen for inducing mixed chimerism in HC transplantation.
- This approach shows potential for achieving transplant tolerance without GVHD.
- Combining TomoTLI with TBI and belatacept proved to be an unacceptable regimen due to fatal GVHD.
