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Durable remission of post-transplant relapsed FLT3-ITD AML in response to gilteritinib administration after a second transplant from the same donor.
International Journal of Hematology ( IF 1.7 ) Pub Date : 2020-03-17 , DOI: 10.1007/s12185-020-02858-1
Toshihiko Ando 1 , Haruna Sano 1 , Masako Yokoo 1 , Kana Kusaba 1 , Keisuke Kidoguchi 1 , Kyosuke Yamaguchi 1 , Hiroo Katsuya 1 , Satoshi Yoshihara 2 , Yasushi Kubota 1, 3 , Kensuke Kojima 1, 4 , Shinya Kimura 1
Affiliation  

Patients with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML) respond to conventional induction chemotherapy, with remission rates similar to those seen in other subtypes; however, they are much more likely to relapse and relapse is rapid. For this reason, eligible patients receive consolidation therapy with early allogenic transplantation, but the recurrence rate remains high, even after transplantation. Moreover, the optimal therapy for patients with FLT3-ITD AML who relapse after allogeneic hematopoietic stem cell transplantation remains unclear. Here, we report a case in which graft-versus-leukemia (GVL) effects were induced by gilteritinib administration after a second transplant from the same donor, resulting in sustained remission of early FLT3-ITD AML relapse after allogeneic transplantation. Several studies suggest that the benefits of FLT3 tyrosine kinase inhibitors (FLT3-TKI) after allogeneic transplantation are attributable to GVL induction, as well as direct effects on FLT3 mutation-positive leukemia cells. With this in mind, we induced lymphodepletion using L-PAM to further enhance GVL induction by donor lymphocytes and FLT3-TKI. We believe that enhancement of GVL induction by lymphodepletion should be considered before FLT3-TKI use, if the prognosis is very poor, such as in patients with recurrence following allogeneic transplantation.



中文翻译:

从同一供体进行第二次移植后,对吉尔替替尼给药后,移植后复发的FLT3-ITD AML持久缓解。

患有FMS样酪氨酸激酶3内部串联重复(FLT3-ITD)急性髓细胞性白血病(AML)的患者对常规诱导化疗有反应,缓解率与其他亚型相似。但是,它们更有可能复发并且复发很快。因此,合格的患者在早期异体移植中接受巩固治疗,但是即使在移植后,复发率仍然很高。而且,对于同种异体造血干细胞移植后复发的FLT3-ITD AML患者的最佳治疗方法仍不清楚。在这里,我们报道了一个案例,其中在同一个供体的第二次移植后,通过吉尔替替尼给药诱导了移植物抗白血病(GVL)效应,导致同种异体移植后早期FLT3-ITD AML复发的持续缓解。几项研究表明,同种异体移植后,FLT3酪氨酸激酶抑制剂(FLT3-TKI)的益处可归因于GVL诱导,以及对FLT3突变阳性白血病细胞的直接影响。考虑到这一点,我们使用L-PAM诱导了淋巴清除,以进一步增强供体淋巴细胞和FLT3-TKI对GVL的诱导。我们认为,如果预后很差,例如同种异体移植后复发的患者,则应在使用FLT3-TKI之前考虑通过淋巴清除术增强GVL诱导。我们使用L-PAM诱导淋巴衰竭,以进一步增强供体淋巴细胞和FLT3-TKI对GVL的诱导。我们认为,如果预后很差,例如同种异体移植后复发的患者,则应在使用FLT3-TKI之前考虑通过淋巴清除术增强GVL诱导。我们使用L-PAM诱导淋巴衰竭,以进一步增强供体淋巴细胞和FLT3-TKI对GVL的诱导。我们认为,如果预后非常差,例如同种异体移植后复发的患者,则应在使用FLT3-TKI之前考虑通过淋巴清除术增强GVL诱导。

更新日期:2020-03-17
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