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- Title
Tomotherapy Applied Total Lymphoid Irradiation and Allogeneic Hematopoietic Cell Transplantation Generates Mixed Chimerism in the Rhesus Macaque Model.
- Authors
Forrest, Lisa; Fechner, John; Post, Jennifer; Van Asselt, Nathaniel; Kvasnica, Kevin; Haynes, Lynn D.; Coonen, Jenny; Brunner, Kevin; Haynes, W. John; Little, Christopher; Burlingham, William J.; Hematti, Peiman; Strober, Samuel; Kaufman, Dixon B.
- Abstract
Development of a new methodology to induce immunological chimerism after allogeneic hematopoietic cell (HC) transplantation in a rhesus macaque model is described. The chimeric state was achieved using a non-myeloablative, helical tomotherapy-based total lymphoid irradiation (TomoTLI) conditioning regimen followed by donor HC infusions between 1-haplotype matched donor/recipient pairs. The technique was tested as a feasibility study in an experimental group of seven rhesus macaques that received the novel TomoTLI tolerance protocol and HC allo-transplants. Two tomotherapy protocols were compared: TomoTLI (n = 5) and TomoTLI/total-body irradiation (TBI) (n = 2). Five of seven animals developed mixed chimerism. Three of five animals given the TomoTLI protocol generated transient mixed chimerism with no graft-versus-host disease (GVHD) with survival of 33, 152 and >180 days. However, the inclusion of belatacept in addition to a single fraction of TBI resulted in total chimerism and fatal GVHD in both animals, indicating an unacceptable conditioning regimen.
- Subjects
TOTAL body irradiation; HEMATOPOIETIC stem cell transplantation; MACAQUES; RHESUS monkeys; CHIMERISM; GRAFT versus host disease; IRRADIATION
- Publication
Radiation Research, 2021, Vol 196, Issue 6, p623
- ISSN
0033-7587
- Publication type
Article
- DOI
10.1667/RADE-20-00246.1