2024-03-29T01:00:12Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/873152022-11-29T17:26:40Zhdl_2115_20040hdl_2115_121Gilteritinib enhances graft-versus-leukemia effects against FLT3-ITD mutant leukemia after allogeneic hematopoietic stem cell transplantationZhang, ZixuanHasegawa, YutaHashimoto, DaigoSenjo, HajimeKikuchi, RyoChen, XuanzhongYoneda, KazukiSekiguchi, TomokoKawase, TatsuyaTsuzuki, HirofumiIshio, TakashiAra, TakahideOhigashi, HiroyukiNakagawa, MasaoTeshima, Takanori490Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative therapy for FLT3 internal tandem duplication mutant (FLT3-ITD+) acute myeloid leukemia, but relapse rate is high. A recent study showed that sorafenib, a first generation FLT3 and multikinase inhibitor, enhanced graft-versus-leukemia (GVL) effects against FLT3-ITD+ leukemia via interleukin-15 (IL-15) production. However, it remains to be clarified whether this effect could be mediated by selective FLT3 inhibition. We investigated whether gilteritinib, a selective FLT3 inhibitor, could enhance GVL effects against FLT3-ITD transfected Ba/F3 leukemia (Ba/F3-FLT3-ITD) in mice. Oral administration of gilteritinib from day +5 to +14 after allo-SCT reduced expression of the co-inhibitory receptors PD-1 and TIGIT on donor CD8(+) T cells and enhanced IL-15 expression in Ba/F3-FLT3-ITD. Bioluminescent imaging using luciferase-transfected Ba/F3-FLT3-ITD demonstrated that gilteritinib significantly suppressed leukemia expansion after allo-SCT, whereas it did not impact the morbidity or mortality of graft-versus-host disease (GVHD), resulting in significant improvement of overall survival. In conclusion, short-term administration of gilteritinib after allo-SCT enhanced GVL effects against FLT3-ITD+ leukemia without exacerbating GVHD.Springer NatureJournal Articleapplication/pdfhttp://hdl.handle.net/2115/87315https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/87315/2/24292_2_merged_1644504406.pdf0268-3369Bone marrow transplantation5757757802022-05-01enginfo:doi/10.1038/s41409-022-01619-4author