Tomotherapy Applied Total Lymphoid Irradiation and Allogeneic Hematopoietic Cell Transplantation Generates Mixed Chimerism in the Rhesus Macaque Model

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.

Conditioning with TLI/ATG in Hematopoietic Stem Cell Transplantation from Haploidentical Donors with Post-transplant Cyclophosphamide in Children in a Single Center During 2015-2017

Hematopoietic stem cell transplantation is a treatment alternative for some benign blood disorders. The use of nonmyeloablative con- ditioning with total lymphoid irradiation and anti-thymocyte globulin has decreased the incidence of acute graft-versus-host disease and can reduce the complications of total body irradiation and generate sustained chimerism. Posttransplant cyclophosphamide has also shown benefits. This is a retrospective, case-series study of pediatric patients with benign pathologies who were treated at Fundación Valle del Lili. A descriptive analysis was performed with measures of central tendency. Survival outcomes were calculated using the Kaplan-Meier estimator. Twelve patients (50% female) with benign blood disorders were included, with an average age of 8.2 ± 5.7 years. The type of donor was haploidentical in all cases; in half, the cellular source was bone marrow. Fifty percent had a diagnosis of immunodeficiencies. The average follow-up time was 28.9 months. The total lymphoid irradiation dose corresponded to a median of 750 centigrays (IQR: 400-750). Neutrophil grafting was achieved in 12/12 patients, and platelet grafting was achieved in 11/12 patients. The presentation of acute graft-versus-host disease was 58%. The transplant related mortality was 17%, and the 1-year overall survival was 83%. Conditioning with total lymphoid irradiation and anti-thymocyte globulin and the use of posttransplant cyclophosphamide is a viable alternative; however, it did not decrease the cases of acute graft-versus-host disease. Keywords: Stem cell transplant, Thymoglobulin, Lymphatic irradiation, Child, Adolescent