Effect of lethal total body irradiation on bone marrow chimerism, acute graft-versus-host disease, and tumor engraftment in mouse models: impact of different radiation techniques using low- and high-energy X-rays.

Abstract

Effects of X‑ray energy levels used for myeloablative lethal total body irradiation (TBI) delivery prior to bone marrow transplantation (BMT) in preclinical mouse models were examined. In mouse models, single-fraction myeloablative TBI at alethal dose was delivered using two different X‑ray devices, either low (160 kV cabinet irradiator) or high energy (6MV linear accelerator), before semi-allogeneic hematopoietic stem-cell transplantation (HSCT) to ensure bone marrow (BM) chimerism, graft-versus-host disease (GVHD), and tumor engraftment. Recipient mice were clinically followed for 80days after bone marrow transplantation (BMT). Flow cytometry was performed to assess donor chimerism and tumor engraftment in recipient mice. Both X‑ray irradiation techniques delivered a10 Gy single fraction of TBI, presented alethal effect, and could allow near-complete early donor chimerism on day13. However, low-energy irradiation increased Tcells' alloreactivity compared to high-energy irradiation, leading to clinical consequences for GVHD and tumor engraftment outcomes. The alloreactive effect differences might be attributed to the distinction in inflammatory status of irradiated recipients at donor cell infusion (D0). Delaying donor cell administration (D1 after lethal TBI) attenuated Tcells' alloreactivity and clinical outcomes in GVHD mouse models. Different X‑ray irradiation modalities condition Tcell alloreactivity in experimental semi-allogeneic BMT. Low-energy X‑ray irradiator induces apost-TBI inflammatory burst and exacerbates alloreactive reactions. This technical and biological information should be considered in interpreting GVHD/ graft-versus-leukemia effect results in mice experimental models of BMT.