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同种异体二次移植后接受吉特替尼治疗后,FLT3-ITD AML 移植后复发患者获得持久缓解。

Durable remission of post-transplant relapsed FLT3-ITD AML in response to gilteritinib administration after a second transplant from the same donor.

机构信息

Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.

Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

出版信息

Int J Hematol. 2020 Aug;112(2):249-253. doi: 10.1007/s12185-020-02858-1. Epub 2020 Mar 17.

Abstract

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.

摘要

携带 FMS 样酪氨酸激酶 3 内部串联重复(FLT3-ITD)的急性髓系白血病(AML)患者对常规诱导化疗有反应,缓解率与其他亚型相似;然而,他们更有可能复发,且复发迅速。出于这个原因,符合条件的患者接受早期同种异体移植的巩固治疗,但即使在移植后,复发率仍然很高。此外,对于接受异基因造血干细胞移植后复发的 FLT3-ITD AML 患者,最佳治疗方法仍不清楚。在这里,我们报告了一例在第二次来自同一供体的移植后,通过吉特替尼给药诱导移植物抗白血病(GVL)效应,导致异基因移植后早期 FLT3-ITD AML 复发的持续缓解。几项研究表明,FLT3 酪氨酸激酶抑制剂(FLT3-TKI)在异基因移植后的益处归因于 GVL 诱导以及对 FLT3 突变阳性白血病细胞的直接作用。考虑到这一点,我们使用 L-PAM 进行淋巴细胞耗竭,以进一步增强供体淋巴细胞和 FLT3-TKI 的 GVL 诱导。我们认为,如果预后非常差,例如在异基因移植后复发的患者中,在使用 FLT3-TKI 之前,应该考虑通过淋巴细胞耗竭增强 GVL 诱导。

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