| Literature DB >> 35228711 |
Zixuan Zhang1, Yuta Hasegawa1, Daigo Hashimoto2, Hajime Senjo1, Ryo Kikuchi1, Xuanzhong Chen1, Kazuki Yoneda1, Tomoko Sekiguchi1, Tatsuya Kawase3, Hirofumi Tsuzuki3, Takashi Ishio1, Takahide Ara1, Hiroyuki Ohigashi1, Masao Nakagawa1, Takanori Teshima1.
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.Entities:
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Year: 2022 PMID： 35228711 DOI： 10.1038/s41409-022-01619-4
Source DB: PubMed Journal: Bone Marrow Transplant ISSN： 0268-3369 Impact factor: 5.483