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对于急性髓系白血病且核型正常的患者,采用清髓性化疗并继以自体干细胞输注,可能会克服FLT3(胎儿肝酪氨酸激酶3)突变带来的不良预后影响。

Myeloablative chemotherapy followed by autologous stem cell infusion may overcome the adverse prognostic impact of FLT3 (foetal liver tyrosine kinase 3) mutations in patients with acute myeloid leukaemia and normal karyotype.

作者信息

Palmieri Salvatore, Ferrara Felicetto, Leoni Franco, Ciolli Stefania, Pollio Filiberto, D'Amico Maria Rosaria, Celentano Maria, Viola Assunta, Vicari Laura, Izzo Barbara, Pane Fabrizio

机构信息

Division of Haematology and Stem cell Transplantation Unit, Cardarelli Hospital, Naples, Italy.

出版信息

Hematol Oncol. 2007 Mar;25(1):1-5. doi: 10.1002/hon.794.

DOI:10.1002/hon.794
PMID:17036374
Abstract

In this study, we analysed the prognostic relevance of foetal liver tyrosine kinase 3 (FLT3) mutations in 73 patients with acute myeloid leukaemia (AML) with normal karyotype, who survived induction and consolidation and received autologous stem cell transplantation (ASCT) after successful mobilization of peripheral blood stem cell (PBSC). There were 44 males and 29 females with a median age of 54 years (range 20-77). Overall, 16 out of 73 autografted patients (22%) had FLT3 mutations. More in detail, FLT3/ITDs were detected in 10 out of 73 patients (14%), while FLT3 D835 mutations were detected in five cases (7%). One patient (1%) was found as having both abnormalities. White blood cell count (p=0.009), serum concentration of lactate dehydrogenase (p=0.01), and percentages of peripheral blood (p=0.002) and bone marrow blasts (p=0.03) were significantly higher in patients showing the FLT3 mutations. On the contrary, overall survival and disease-free survival were similar between patients with or without FLT3 mutations (p=0.73 and 0.78, respectively). In conclusion, our data suggest that myeloablative chemotherapy supported by auto-PBSCT may overcome the adverse prognostic implications of FLT3 mutations in AML. However, it is to consider that autografted patients are highly selected for best response to induction, consolidation and mobilization, as well as for minor non-haematologic toxicity.

摘要

在本研究中,我们分析了73例核型正常的急性髓系白血病(AML)患者中胎儿肝酪氨酸激酶3(FLT3)突变的预后相关性,这些患者诱导缓解和巩固治疗后存活,并在成功动员外周血干细胞(PBSC)后接受了自体干细胞移植(ASCT)。其中男性44例,女性29例,中位年龄54岁(范围20 - 77岁)。总体而言,73例接受自体移植的患者中有16例(22%)存在FLT3突变。更详细地说,73例患者中有10例(14%)检测到FLT3内部串联重复(FLT3/ITD),5例(7%)检测到FLT3 D835突变。1例患者(1%)同时存在这两种异常。FLT3突变患者的白细胞计数(p = 0.009)、血清乳酸脱氢酶浓度(p = 0.01)以及外周血(p = 0.002)和骨髓原始细胞百分比(p = 0.03)显著更高。相反,有或无FLT3突变患者的总生存期和无病生存期相似(分别为p = 0.73和0.78)。总之,我们的数据表明,自体PBSCT支持的清髓性化疗可能克服AML中FLT3突变的不良预后影响。然而,需要考虑的是,自体移植患者是经过高度筛选的,对诱导、巩固和动员治疗反应最佳,且非血液学毒性较小。

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Myeloablative chemotherapy followed by autologous stem cell infusion may overcome the adverse prognostic impact of FLT3 (foetal liver tyrosine kinase 3) mutations in patients with acute myeloid leukaemia and normal karyotype.对于急性髓系白血病且核型正常的患者,采用清髓性化疗并继以自体干细胞输注,可能会克服FLT3(胎儿肝酪氨酸激酶3)突变带来的不良预后影响。
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引用本文的文献

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Overcoming Resistance to FLT3 Inhibitors in the Treatment of -Mutated AML.克服 FLT3 抑制剂在治疗突变型 AML 中的耐药性。
Int J Mol Sci. 2020 Feb 24;21(4):1537. doi: 10.3390/ijms21041537.
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The role of FLT3 inhibitors as maintenance therapy following hematopoietic stem cell transplant.FLT3抑制剂在造血干细胞移植后作为维持治疗的作用。
Leuk Res Rep. 2018 Jul 19;10:26-36. doi: 10.1016/j.lrr.2018.06.003. eCollection 2018.