初治360例急性早幼粒细胞白血病临床特征及预后分析

发布时间：2018-05-16 02:08

本文选题：急性早幼粒细胞白血病 + 维A酸　；参考：《吉林大学》2017年硕士论文

【摘要】：目的:研究单中心360例APL患者的临床特征及治疗效果(近期效果和远期效果),分析影响APL治疗效果的预后因素。方法:回顾性分析2009年1月至2016年5月于吉林大学第一医院肿瘤中心就诊的360例初治APL患者资料,患者经诱导、巩固、维持治疗,于治疗后第21~28天行骨穿评价治疗效果,将完成诱导治疗的患者纳入生存分析。结果:本研究纳入360例患者,其中低危组59例(占16.4%)、中危组204例(占56.7%)、高危组97例(占26.9%),三组患者在血红蛋白水平(F=0.438,P=0.153)、活化部分凝血活没时间APTT(F=0.46,P=0.727)、凝血酶原时间PT(F=0.95,P=0.608)、纤维蛋白原FBG1.0 g/L所占比例(c2=1.27,P=0.53),无统计学意义;而在年龄(F=97.08,P0.001)、FBG水平(F=13.49,P=0.012)、纤维蛋白原1.5 g/L所占比例(c2=9.79,P=0.007)、PML-RARαS型(c2=12.15,P=0.02),差异有统计学意义。在初诊的360例患者中,3例放弃治疗,29例早期死亡,余328例达CR,无耐药相关的治疗失败。早期死亡主要原因为脑出血(65.5%),早期死亡与获得CR的患者临床特征相比,在初诊时高白细胞计数(P=0.01)、低血小板计数(P=0.04)、高危组(P0.001)方面差异有统计学意义,而PML-RARα融合基因L、S型、FLT3-TID(+)差异无统计学意义。低、中、高三组患者的CR率分别为98.3%、95.1%、80.9%,高危组患者CR率与低、中危组相比差异具有统计学意义(c2=21.41,P0.001)。328例获得CR的患者,27例未行巩固治疗,余301例患者中290例患者在我院接受了2~3个疗程的巩固治疗。分子生物学完全缓解率为99.2%(264/266)。中位达分子生物学转阴的疗程数为2。低、中、高三组患者达分子生物学转阴的疗程数分别为2.3±1.9、2.1±0.8和2.2±1.0,差异无统计学意义(F=0.094,P=0.516)。高危组应用中/大剂量阿糖胞苷的患者32例(47.1%),中位达分子生物学转阴的疗程数为2.2±1.1,应用其他治疗方案分子生物学转阴的疗程数为2.3±1.0,两者差异无统计学意义(t=0.08,P=0.936)。中位随访时间33个月(3~91个月),3年的OS率和RFS率分别为95.4%和91.6%。对可能影响APL预后的因素如年龄、性别、初诊白细胞计数、危险分层、FLT3-ITD阳性、CD56表达、PML-RARα融合基因L型、S型等纳入单因素分析。对于OS:CD56阳性表达患者的OS率明显低于对照组(P=0.024),巩固治疗中不加维A酸组OS率明显低于加维A酸组(P=0.013),而其他因素对OS的影响差异无统计学意义。对于RFS:初诊白细胞数≥10×109/L的患者明显低于初诊白细胞10×109/L(P=0.017),危险分层的高危组RFS率明显低于低、中危组(P=0.035),CD56阳性表达患者的RFS率明显低于对照组(P=0.004),巩固治疗中不加维A酸组RFS率明显低于加维A酸组(P=0.013),达分子生物学缓解的疗程数≥3的患者RFS率明显低于1疗程或2疗程(P=0.035),其他因素的影响差异无统计学意义。将对OS与RFS预后有影响的单因素纳入多因素分析,结果显示,CD56是影响APL患者OS的独立危险因素,初诊白细胞数、危险分层、CD56表达是影响RFS的独立危险因素。结论:1.本研究的APL患者总体CR率为91.9%,其中低、中、高三组患者的CR率分别为98.3%、95.1%和80.9%(c2=21.41,P0.001)。分子生物学完全缓解率为99.2%(264/266)。2.患者的早期死亡率为8.1%,高危组患者早期死亡率高达19.1%,与达到CR的患者相比,差异有统计学意义的为初诊时高白细胞计数(P=0.01)、低血小板数(P=0.04),危险分层中高危组(P0.001),而PML-RARα融合基因L、S及FLT3-TID(+)无统计学意义。3.生存分析:共286例患者纳入生存分析,3年OS率和RFS率分别为95.4%和91.6%。单因素分析:影响OS的因素为CD56表达、巩固治疗中加或不加维A酸;影响RFS的为初诊白细胞数、危险分层、巩固治疗中加或不加维A酸、达分子生物学缓解的疗程数。多因素分析:影响OS的预后因素为CD56表达,影响RFS的预后因素为初诊白细胞数、危险分层、CD56表达。
[Abstract]:Objective: To study the clinical features and therapeutic effect (short-term effect and long-term effect) of 360 APL patients in a single center, and to analyze the prognostic factors affecting the effect of APL. Methods: a retrospective analysis of the data of 360 cases of primary APL patients in the cancer center of No.1 Hospital of Jilin University from January 2009 to May 2016 was analyzed, and the patients were induced, consolidated and maintained. 21~28 days after treatment, the effect of bone wear evaluation was performed, and the patients completed the induction therapy were included in the survival analysis. Results: This study included 360 patients, including 59 in low risk group (16.4%), 204 in middle risk group (56.7%), 97 in high risk group (26.9%) and three in hemoglobin level (P=0.153), and activated partial coagulation time A PTT (F=0.46, P=0.727), prothrombin time PT (F=0.95, P=0.608), the proportion of fibrinogen FBG1.0 g/L (c2=1.27, P=0.53), no statistical significance, but in age (F=97.08, P0.001), fibrinogen, the proportion of fibrinogen, the difference is statistically significant. Of the 360 patients with primary diagnosis, 3 were given up treatment, 29 died early, 328 were CR, and no drug resistance related treatment failed. The main cause of early death was cerebral hemorrhage (65.5%). Early death was compared with the clinical features of CR, high white cell count (P= 0.01), low platelet count (P=0.04), and high risk group (P0.001) at first diagnosis. Statistical significance, but the PML-RAR alpha fusion gene L, S, FLT3-TID (+) difference was not statistically significant. The CR rate in the lower, middle and high three groups were 98.3%, 95.1%, 80.9% respectively. The rate of CR in the high-risk group was lower than that in the middle risk group, and the difference was statistically significant (c2=21.41, P0.001) in.328 cases received CR, 27 cases were not consolidated, and the remaining 301 patients were 290. The patients received a 2~3 course of consolidation therapy in our hospital. The total remission rate of molecular biology was 99.2% (264/266). The course number of middle molecular biology turned negative for molecular biology was 2. low. The number of treatment courses in the middle and high three groups was 2.3 + 1.9,2.1 + 0.8 and 2.2 + 1 respectively. There was no statistical difference (F=0.094, P=0.516). 32 cases (47.1%) were treated with medium / large dose cytarabine. The number of course of middle molecular biology turned negative was 2.2 + 1.1. The number of treatment courses was 2.3 + 1 with other therapies. The difference was not statistically significant (t=0.08, P=0.936). The median follow-up time was 33 months (3~91 months), and the OS rate and RFS rate of 3 years were 95.4%, respectively. The factors that might affect the prognosis of APL, such as age, sex, initial leukocyte count, risk stratification, FLT3-ITD positive, CD56 expression, PML-RAR alpha fusion gene L, S type, were included in the single factor analysis. The OS rate for OS:CD56 positive patients was significantly lower than that in the control group (P= 0.024), and the OS rate in the unmodified A acid group was significantly lower than that of the Guci in the consolidation therapy. There was no significant difference in the effect of other factors on the effect of A acid group (P=0.013) on OS. For patients with primary leukocyte number more than 10 * 109/L, 10 x 109/L (P=0.017) was significantly lower than that of first diagnosed leukocyte. The RFS rate in high-risk group was significantly lower than that in low risk group (P=0.035). The RFS rate of the positive expression of CD56 was significantly lower than that of the control group (P=0.004). In the treatment, the rate of RFS in the A group was significantly lower than that of the vitamin A group (P=0.013). The RFS rate of the patients with the molecular biological remission of more than 3 was significantly lower than that of the 1 course or 2 course of treatment (P=0.035). There was no significant difference in the influence of other factors. The single factor affecting the prognosis of OS and RFS was included in the multivariate analysis. The results showed that CD56 was the influence of APL. The independent risk factors of patients with OS, primary leukocyte count, risk stratification and CD56 expression are independent risk factors for RFS. Conclusion: the overall CR rate of APL patients in 1. studies was 91.9%, of which the rate of CR was 98.3%, 95.1% and 80.9% (c2=21.41, P0.001) in the lower, middle and high three groups respectively. The total remission rate of the molecular biology was 99.2% (264/266).2. patients. Early mortality was 8.1%, and early mortality in high-risk groups was 19.1%. Compared with CR patients, there were significant differences in high white cell count (P=0.01), low platelet count (P=0.04), high-risk group (P0.001), PML-RAR alpha fusion gene L, S and FLT3-TID (+) without statistically significant.3. survival analysis: a total of 286 cases. The patients were included in the survival analysis. The 3 year OS rate and the RFS rate were respectively 95.4% and 91.6%. single factor analysis. The factors affecting OS were CD56 expression, plus or without adding vitamin A acid; the number of primary leukocytes, the risk stratification, the consolidation of the treatment and the number of treatment courses in the treatment of molecular biological remission. The later factor was CD56 expression, and the prognostic factors of RFS were the number of newly diagnosed white blood cells, risk stratification and CD56 expression.

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

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