本文選題：急性髓系白血病　切入點：FLT3-ITD　出處：《浙江大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的研究高三尖杉酯堿為主的聯(lián)合化療方案對染色體為正常核型的FLT3-ITD突變急性髓細(xì)胞白血病(AML)患者(除急性早幼粒細(xì)胞白血病)的療效與安全性,并比較了該方案對于FLT3-ITD野生型的AML患者的療效。方法回顧性分析了 2010年1月至2016年1月期間浙江大學(xué)醫(yī)學(xué)院附屬第一醫(yī)院收治的初發(fā)急性髓細(xì)胞白血病患者,選擇其中染色體為正常核型且檢測過FLT3-ITD突變的患者,對未進(jìn)行誘導(dǎo)化療及隨訪資料不全患者進(jìn)行刪除。研究分析了這些患者化療后的CR率及OS。依據(jù)誘導(dǎo)方案中是否含有高三尖杉酯堿進(jìn)行分組,對比分析含有高三尖杉酯堿的誘導(dǎo)化療方案對FLT3-ITD突變患者預(yù)后的影響。同時,分析了 FLT3-ITD突變AML患者的臨床表現(xiàn)。結(jié)果2010年1月至2016年1月期間浙江大學(xué)醫(yī)學(xué)院附屬第一醫(yī)院收治的初發(fā)急性髓細(xì)胞白血病患者(除急性早幼粒細(xì)胞白血病)共588例,其中正常核型患者350例,占59.6%。除外因非醫(yī)學(xué)相關(guān)原因或早期死亡未完成誘導(dǎo)化療的46例患者,余304例患者中FLT3突變患者58例,占19.1%,FLT3-ITD突變陽性患者初發(fā)時表現(xiàn)為高白細(xì)胞(100×109/L)比例顯著高于野生型患者,FLT3-ITD突變患者伴有NPM1突變比例顯著高于未突變患者。58名FLT3-ITD突變患者中接受含高三尖杉酯堿的誘導(dǎo)方案進(jìn)行化療的患者18例,包括HAE方案9例,HAA方案5例以及HA方案4例。接受不含高三尖杉酯堿的化療方案包括IA或DA方案治療的39例,另有1例采用AA方案化療。中位隨訪18.87個月。FLT3-ITD突變患者治療前骨髓原始細(xì)胞比例均值為72.9±2.36%,野生型比例為59.4±1.49%,p0.001;突變組患者外周血白細(xì)胞均值為76.21±8.8×109/L,野生型為37.2±3.5×109/L,p=0.002。FLT3-ITD突變患者58人首次誘導(dǎo)緩解率為39.7%,其中不含高三尖杉酯堿誘導(dǎo)方案組緩解率為45%,含高三尖杉酯堿組緩解率為27.8%,二者無顯著差異,p=0.215;2療程化療后緩解率為60.3%,其中不含高三尖杉酯堿誘導(dǎo)方案組緩解率為62.5%,含高三尖杉酯堿組緩解率為55.6%,二者無顯著差異,p=0.773,其中非高三尖杉酯堿組中位生存時間14.6±3.11月,而高三尖杉酯堿組中位生存時間未達(dá)到,二者間未見顯著差異,p=0.900。結(jié)論FLT3-ITD突變是AML的獨立危險因素,本研究發(fā)現(xiàn)該突變在正常核型患者中發(fā)生率為19.1%,具有發(fā)病時外周白細(xì)胞計數(shù)高、骨髓原始細(xì)胞比例高的臨床特點,易合并有NPM1突變。FLT3-ITD突變患者初治CR率及OS均低于未突變患者,其中合并NPM1突變者CR率與FLT3-ITD未突變患者無顯著差異,但OS可能存在差異。以高三尖杉酯堿為主的聯(lián)合化療方案不能改善FLT3-ITD突變患者的完全緩解率和OS。
[Abstract]:Objective to study the combined chemotherapy of homoharringtonine based mutation in acute myeloid leukemia of chromosomes as normal karyotype FLT3-ITD (AML) patients (except for acute promyelocytic leukemia) and the clinical efficacy and safety, and compare the curative effect of AML patients with the scheme for the wild type FLT3-ITD. Methods a retrospective analysis of patients primary acute myeloid leukemia treated in the First Affiliated Hospital of Medical College of Zhejiang University during the period from January 2010 to January 2016, the normal karyotype and chromosome detection of FLT3-ITD mutations in patients of induced chemotherapy and follow-up data were not deleted. Of these patients after chemotherapy, CR rate and OS. basis by scheme whether it contains homoharringtonine group, comparative analysis of effect of induction chemotherapy with homoharringtonine on prognosis of patients with FLT3-ITD mutations. When analyzing FLT3-ITD mutation of clinical manifestations of AML patients. The First Affiliated Hospital during the period from January 2010 to January 2016 at the Zhejiang University School of medicine in primary acute myeloid leukemia patients (except for acute promyelocytic leukemia) a total of 588 cases, including 350 cases of patients with normal karyotype, accounting for 59.6%. in addition to external non medical reasons related to early death or not 46 cases of induction chemotherapy patients, more than 304 cases of patients with FLT3 mutations in 58 cases, accounting for 19.1%, FLT3-ITD mutation positive patients with primary performance high white blood cells (100 * 109/L) was significantly higher than that of wild type patients, patients with FLT3-ITD mutations associated with NPM1 mutation was higher than that without mutation in patients with.58 patients with FLT3-ITD mutations accept the induction regimen containing homoharringtonine chemotherapy in 18 cases, including 9 cases of HAE, 4 cases HAA 5 cases and HA scheme. Accept without homoharringtonine chemotherapy The scheme includes 39 cases of treatment of IA or DA regimen, and 1 cases were treated with AA chemotherapy. The median follow-up was 18.87 months before treatment in patients with the.FLT3-ITD mutation percentage of bone marrow blasts mean was 72.9 + 2.36%, 59.4 + 1.49% the proportion of wild type and p0.001 mutation group; peripheral blood cell of patients with a mean of 76.21 + 8.8 * 109/L, wild type was 37.2 + 3.5 * 109/L, p=0.002.FLT3-ITD mutation in 58 patients with first complete remission rate was 39.7%, which does not contain homoharringtonine induced group remission rate was 45%, including homoharringtonine group and the remission rate was 27.8%, no significant difference between the two p= 0.215; after 2 cycles of chemotherapy the remission rate was 60.3%, which does not contain homoharringtonine induced group remission rate was 62.5%, including homoharringtonine group and the remission rate was 55.6%, no significant difference between the two p=0.773, including non homoharringtonine group, the median survival time was 14.6 + 3.11 months, and homoharringtonine group Does not meet the survival time, there were no significant differences among the two p=0.900., the FLT3-ITD mutation is an independent risk factor of AML, this study found that the mutation in normal karyotype in patients with incidence of 19.1%, with the onset of peripheral white blood cell count, clinical features of higher percentage of bone marrow blast cells, usually associated with mutations in NPM1.FLT3-ITD the mutation rate of OS and CR patients were lower than those of non mutation patients with NPM1 mutation rate of CR and FLT3-ITD patients without mutations had no significant difference, but OS may be different. No chemotherapy combined with homoharringtonine mainly improved the complete remission rate and OS. mutation in FLT3-ITD patients

【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R733.71

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