| Title: | Gilteritinib enhances graft-versus-leukemia effects against FLT3-ITD mutant leukemia after allogeneic hematopoietic stem cell transplantation |
| Authors: | Zhang, Zixuan Browse this author |
| Hasegawa, Yuta Browse this author |
| Hashimoto, Daigo Browse this author →KAKEN DB |
| Senjo, Hajime Browse this author |
| Kikuchi, Ryo Browse this author |
| Chen, Xuanzhong Browse this author |
| Yoneda, Kazuki Browse this author |
| Sekiguchi, Tomoko Browse this author |
| Kawase, Tatsuya Browse this author |
| Tsuzuki, Hirofumi Browse this author |
| Ishio, Takashi Browse this author |
| Ara, Takahide Browse this author |
| Ohigashi, Hiroyuki Browse this author |
| Nakagawa, Masao Browse this author →KAKEN DB |
| Teshima, Takanori Browse this author →KAKEN DB |
| Issue Date: | 1-May-2022 |
| Publisher: | Springer Nature |
| Journal Title: | Bone marrow transplantation |
| Volume: | 57 |
| Issue: | 5 |
| Start Page: | 775 |
| End Page: | 780 |
| Publisher DOI: | 10.1038/s41409-022-01619-4 |
| Abstract: | Allogeneic 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. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/87315 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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