Effects of Ultra-High Dose-Rate Radiotherapy (FLASH-RT) on the Hematopoietic and Immune Systems: An Animal Study

Ultra-high dose-rate radiotherapy, also known as FLASH radiotherapy (FLASH-RT), reduces radiation-induced damage in several organs. This study aimed to compare the effects of FLASH-RT and conventional dose-rate radiotherapy (CONV-RT) at 3 Gy and 5 Gy of total-body irradiation (TBI) on the survival of the hematopoietic system, peripheral blood cells, and immune-related responses. C57BL/6N male mice were divided into controls (0 Gy), FLASH-RT (109 Gy/s), and CONV-RT (0.067 Gy/s) groups. FLASH-RT was performed using the DIRAMS LINAC, producing 6-MeV electron beams. Irradiated mice were sacrificed on days 1, 2, 4, 7, 14, 21, and 28 after TBI at 3 Gy and 5 Gy. Peripheral blood cell counts were not significantly different between the FLASH-RT and CONV-RT groups, except for platelets on days 2-28 after 5 Gy TBI. FLASH-RT initially caused a greater reduction in myeloblasts in bone marrow, platelets and eosinophils in peripheral blood than CONV-RT. The white pulp area in the spleen decreased from days 1-7 after TBI, but gradually increased from day 14 after FLASH-RT, with the white pulp area in the FLASH-RT group being significantly larger than that in the CONV-RT group at day 14 and 28. The T-lymphocytes of the CONV-RT group recovered less than those of the FLASH-RT group at day 14 after 3 Gy and at day 28 after 5 Gy, respectively. FLASH-RT can induce similar damage and recovery patterns in the hematopoietic system as CONV-RT, but FLASH-RT might cause a faster recovery of T-lymphopenia than CONV-RT.