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FLT3 内部串联重复不影响 AML 患者接受单倍体相合异基因造血干细胞移植后的预后。

FLT3 internal tandem duplication does not impact prognosis after haploidentical allogeneic hematopoietic stem cell transplantation in AML patients.

机构信息

Peking University People's Hospital, Peking University Institute of Hematology, Beijing, P.R. China.

Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Diseases, Beijing, P.R. China.

出版信息

Bone Marrow Transplant. 2019 Sep;54(9):1462-1470. doi: 10.1038/s41409-019-0456-x. Epub 2019 Feb 1.

Abstract

Acute myelogenous leukemia (AML) patients with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) have poor prognoses if treated with chemotherapy only, primarily as they experience increased relapse rates. To determine whether this alteration also affects outcomes after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT), we compared 334 consecutive FLT3-ITD-positive vs -negative patients with AML (other than acute promyelocytic leukemia) who underwent HID-HSCT. FLT3-ITD was detected in 39 of 334 patients (11.7%). The 2-year relapse rates for FLT3-ITD-positive and -negative patients were 16% and 17%, respectively (P = 0.774). The 3-year disease-free survival (DFS) rates for FLT3-ITD-positive and -negative patients were 74% (95% confidence interval [CI]: 64-81) and 73% (95% CI: 70-81), respectively; P = 0.872); while the 3-year overall survival (OS) rates were 72% (95% CI: 67-81) and 77% (95% CI: 72-84), respectively (P = 0.862). FLT3-ITD mutation had no influence on non-relapse mortality (NRM 15% vs 14%, P = 0.463). Multivariate analyses showed that disease status at HSCT and white blood cell count at diagnosis were independent risk factors associated with relapse, DFS, and OS. In conclusion, FLT3 mutation status has no impact on outcomes after HID-HSCT in patients with AML. HID-HSCT is therefore a valid option for AML patients with FLT3-ITD mutation.

摘要

急性髓系白血病(AML)患者如果仅接受化疗治疗,且存在胎肝酪氨酸激酶 3(FLT3)内部串联重复(ITD),则预后较差,主要是因为他们的复发率增加。为了确定这种改变是否也会影响 HLA 半相合供体(HID)异基因造血干细胞移植(allo-HSCT)后的结果,我们比较了 334 例连续的 AML(不包括急性早幼粒细胞白血病)FLT3-ITD 阳性和阴性患者接受 HID-HSCT 的情况。在 334 例患者中,有 39 例(11.7%)检测到 FLT3-ITD。FLT3-ITD 阳性和阴性患者的 2 年复发率分别为 16%和 17%(P=0.774)。FLT3-ITD 阳性和阴性患者的 3 年无病生存率(DFS)分别为 74%(95%置信区间[CI]:64-81)和 73%(95% CI:70-81),P=0.872);3 年总生存率(OS)分别为 72%(95% CI:67-81)和 77%(95% CI:72-84),P=0.862)。FLT3-ITD 突变对非复发死亡率(NRM 15%比 14%,P=0.463)没有影响。多因素分析显示,HSCT 时疾病状态和诊断时白细胞计数是与复发、DFS 和 OS 相关的独立危险因素。总之,FLT3 突变状态对 AML 患者接受 HID-HSCT 后的结果没有影响。因此,HID-HSCT 是 FLT3-ITD 突变的 AML 患者的一种有效选择。

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