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

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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)
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)

Submitter: 橋本 大吾

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