Gilteritinib enhances graft-versus-leukemia effects against FLT3-ITD mutant leukemia after allogeneic hematopoietic stem cell transplantation

Zhang, Zixuan; Hasegawa, Yuta; Hashimoto, Daigo et al.

Bone marrow transplantation, 2022, 57(5), 775-780

Permalink : https://hdl.handle.net/2115/87315

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アクセス権
open access
URI
https://hdl.handle.net/2115/87315
タイトル
Gilteritinib enhances graft-versus-leukemia effects against FLT3-ITD mutant leukemia after allogeneic hematopoietic stem cell transplantation
著者
Zhang, Zixuan ; Hasegawa, Yuta ; Hashimoto, Daigo ; Senjo, Hajime ; Kikuchi, Ryo ; Chen, Xuanzhong ; Yoneda, Kazuki ; Sekiguchi, Tomoko ; Kawase, Tatsuya ; Tsuzuki, Hirofumi ; Ishio, Takashi ; Ara, Takahide ; Ohigashi, Hiroyuki ; Nakagawa, Masao ; Teshima, Takanori
著者名
Zhang, Zixuan
著者名
Hasegawa, Yuta
e-Rad_Researcher
20419576
著者名
Hashimoto, Daigo
著者名
Senjo, Hajime
著者名
Kikuchi, Ryo
著者名
Chen, Xuanzhong
著者名
Yoneda, Kazuki
著者名
Sekiguchi, Tomoko
著者名
Kawase, Tatsuya
著者名
Tsuzuki, Hirofumi
著者名
Ishio, Takashi
著者名
Ara, Takahide
著者名
Ohigashi, Hiroyuki
e-Rad_Researcher
80435859
著者名
Nakagawa, Masao
e-Rad_Researcher
40284096
著者名
Teshima, Takanori
言語
英語
発行日
2022-05-01
出版者
Springer Nature
収録物名
Bone marrow transplantation
巻(号)
57(5)
ページ
775-780
抄録
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.
資源タイプ
学術雑誌論文
出版タイプ
Accepted Manuscript
PISSN
0268-3369
関連情報 (isVersionOf)
出版社版DOI
https://doi.org/10.1038/s41409-022-01619-4