含高三尖杉酯碱的诱导化疗方案对伴FLT-ITD突变急性髓系白血病患者疗效分析

发布时间：2018-03-22 11:37

本文选题：急性髓系白血病　切入点：FLT3-ITD　出处：《浙江大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的研究高三尖杉酯碱为主的联合化疗方案对染色体为正常核型的FLT3-ITD突变急性髓细胞白血病(AML)患者(除急性早幼粒细胞白血病)的疗效与安全性,并比较了该方案对于FLT3-ITD野生型的AML患者的疗效。方法回顾性分析了 2010年1月至2016年1月期间浙江大学医学院附属第一医院收治的初发急性髓细胞白血病患者,选择其中染色体为正常核型且检测过FLT3-ITD突变的患者,对未进行诱导化疗及随访资料不全患者进行删除。研究分析了这些患者化疗后的CR率及OS。依据诱导方案中是否含有高三尖杉酯碱进行分组,对比分析含有高三尖杉酯碱的诱导化疗方案对FLT3-ITD突变患者预后的影响。同时,分析了 FLT3-ITD突变AML患者的临床表现。结果2010年1月至2016年1月期间浙江大学医学院附属第一医院收治的初发急性髓细胞白血病患者(除急性早幼粒细胞白血病)共588例,其中正常核型患者350例,占59.6%。除外因非医学相关原因或早期死亡未完成诱导化疗的46例患者,余304例患者中FLT3突变患者58例,占19.1%,FLT3-ITD突变阳性患者初发时表现为高白细胞(100×109/L)比例显著高于野生型患者,FLT3-ITD突变患者伴有NPM1突变比例显著高于未突变患者。58名FLT3-ITD突变患者中接受含高三尖杉酯碱的诱导方案进行化疗的患者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碱的化疗方案包括IA或DA方案治疗的39例,另有1例采用AA方案化疗。中位随访18.87个月。FLT3-ITD突变患者治疗前骨髓原始细胞比例均值为72.9±2.36%,野生型比例为59.4±1.49%,p0.001;突变组患者外周血白细胞均值为76.21±8.8×109/L,野生型为37.2±3.5×109/L,p=0.002。FLT3-ITD突变患者58人首次诱导缓解率为39.7%,其中不含高三尖杉酯碱诱导方案组缓解率为45%,含高三尖杉酯碱组缓解率为27.8%,二者无显著差异,p=0.215;2疗程化疗后缓解率为60.3%,其中不含高三尖杉酯碱诱导方案组缓解率为62.5%,含高三尖杉酯碱组缓解率为55.6%,二者无显著差异,p=0.773,其中非高三尖杉酯碱组中位生存时间14.6±3.11月,而高三尖杉酯碱组中位生存时间未达到,二者间未见显著差异,p=0.900。结论FLT3-ITD突变是AML的独立危险因素,本研究发现该突变在正常核型患者中发生率为19.1%,具有发病时外周白细胞计数高、骨髓原始细胞比例高的临床特点,易合并有NPM1突变。FLT3-ITD突变患者初治CR率及OS均低于未突变患者,其中合并NPM1突变者CR率与FLT3-ITD未突变患者无显著差异,但OS可能存在差异。以高三尖杉酯碱为主的联合化疗方案不能改善FLT3-ITD突变患者的完全缓解率和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

【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.71

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