老年急性髓系白血病诱导治疗疗效与预后分析

发布时间：2018-08-17 12:09

【摘要】：目的:了解单中心真实世界中,老年AML患者的治疗情况。比较传统化疗方案与地西他滨联合减量化疗方案对老年AML患者的治疗疗效及安全性。对老年AML患者进行预后分析。方法:回顾性分析2009年5月至2016年5月吉林大学第一医院肿瘤中心血液科收治的290例老年AML(非APL)患者的临床、遗传学及分子生物学资料,按WHO诊断标准确诊。筛选完成1个疗程传统化疗方案(包括DA、IA、HA、MA、AA、CAG)或者地西他滨联合减量化疗方案(包括D-CAG、D-HAG、DCA+DA)诱导治疗的患者(共121例),在化疗间歇期骨髓抑制期、恢复期行骨髓穿刺评价疗效,并进行短期疗效分析。接着,筛选其中在2个疗程内达到CR的患者(共54例),纳入长期生存分析及预后分析。结果:在初次诱导治疗时使用传统化疗方案或地西他滨联合减量化疗方案的患者,1疗程CR率为32.23%、2疗程CR率为65.85%;传统化疗组1疗程CR率为29.27%(24/82),2疗程CR率为60.71%(34/56);地西他滨联合减量化疗组1疗程CR率为38.46%(15/39),2疗程CR率为76.92%(20/26)。将治疗1疗程达到CR与未达到CR的患者相比,发现影响CR率的因素为初诊时骨髓原始细胞比例(P=0.014)与初诊时外周血原始细胞比例分别为(P=0.001)。将2疗程达到CR与未达到CR的患者相比,未发现影响其CR率的因素(P0.05)。传统化疗组早期死亡率(6周内)为12.20%(10/82),地西他滨联合减量化疗组早期死亡率(6周内)为7.69%(3/39),其差异无统计学意义(P=0.665)。传统化疗组与地西他滨联合减量化疗组在不良反应方面差异无统计学意义(P0.05)。将在诱导治疗中使用了传统化疗方案或地西他滨联合减量化疗方案,且在2个疗程内达到CR的54例患者纳入生存分析。中位随访时间为15.0个月(1.3~81.6个月),中位生存时间为18.0个月(95%CI:15.1-20.9),中位无复发生存时间为11.0个月(95%CI:7.9-14.1)。1年OS率为62.0%,2年OS率为37.4%。1年RFS率为42.6%,2年RFS率为13.0%。标准化疗组中位生存时间为20个月,中位无复发生存时间为8个月。地西他滨联合减量化疗组中位生存时间为18个月,中位无复发生存时间为14个月。对可能影响老年AML预后的因素如年龄、性别、初诊WBC计数、初诊时骨髓原始细胞比例、初诊时外周血原始细胞比例、预后危险分层、诱导治疗方案等进行分析。单因素分析显示:对于OS,初诊骨髓原始细胞比例≥50%的患者(中位OS期11个月)OS明显低于初诊骨髓原始细胞比例50%的患者(中位OS期20个月)(P=0.003);初诊外周血原始细胞比例≥50%的患者(中位OS期9个月)OS明显低于初诊外周血原始细胞比例50%的患者(中位OS期20个月)(P=0.005);达CR后巩固治疗1疗程的患者(中位OS期4个月)OS明显低于达CR后巩固治疗≥2疗程的患者(中位OS期19个月)(P0.001),而其他因素对OS的影响无统计学意义。对于RFS,初诊骨髓原始细胞比例≥50%的患者(中位RFS期6个月)RFS明显低于初诊骨髓原始细胞比例50%的患者(中位RFS期14个月)(P=0.009);初诊外周血原始细胞比例≥50%的患者(中位RFS期5个月)RFS明显低于初诊外周血原始细胞比例50%的患者(中位RFS期14个月)(P=0.009);达CR后巩固治疗1疗程的患者(中位RFS期2个月)RFS明显低于达CR后巩固治疗≥2疗程的患者(中位RFS期12个月)(P0.001);继发性AML患者(中位RFS期0个月)RFS明显低于原发性AML患者(中位RFS期11个月)(P0.001),而其他因素对RFS的影响无统计学意义。多因素分析显示:影响老年AML患者OS的独立预后因素为骨髓原始细胞比例(P=0.030)、外周血原始细胞比例(P=0.037)及达CR后巩固疗程数(P=0.006);影响老年AML患者RFS的独立预后因素为外周血原始细胞比例(P=0.023)及达CR后巩固疗程数(P=0.001)。结论:1.本组患者染色体检出率为90.13%,其中异常克隆检出率为39.80%。随着年龄的增长,患者不良核型所占比例增高。2.传统化疗组患者CR率为60.71%,地西他滨联合减量化疗组患者CR率为76.92%,两组患者在CR率上差异均无统计学意义(P值均0.05)。3.传统化疗组和地西他滨联合减量化疗组在早期死亡率(6周内)、不良反应方面差异无统计学意义(P值均0.05)。4.将达到CR的54例患者纳入生存分析。中位生存时间为18.0个月(95%CI:15.1-20.9),中位无复发生存时间为11.0个月(95%CI:7.9-14.1)。1年OS率为62.0%,2年OS率为37.4%。1年RFS率为42.6%,2年RFS率为13.0%。传统化疗组与地西他滨联合减量化疗组在长期生存上差异无统计学意义。多因素分析:影响老年AML患者OS的独立预后因素为骨髓原始细胞比例(P=0.030)、外周血原始细胞比例(P=0.037)及达CR后巩固疗程数(P=0.006);影响老年AML患者RFS的独立预后因素为外周血原始细胞比例(P=0.023)及达CR后巩固疗程数(P=0.001)。
[Abstract]:Objective:To investigate the treatment of elderly AML patients in the real world in a single center.To compare the efficacy and safety of traditional chemotherapy regimen with that of dicitabine combined with subtractive therapy regimen in elderly AML patients.To analyze the prognosis of elderly AML patients.Methods:A retrospective analysis was made from May 2009 to May 2016 in the Cancer Center of the First Hospital of Jilin University. 290 elderly patients with AML (non-APL) were diagnosed according to WHO diagnostic criteria according to clinical, genetic and molecular biology data. One course of conventional chemotherapy (including DA, IA, HA, MA, AA, CAG) or combination of dicitabine and subtractive therapy (including D-CAG, D-HAG, DCA+DA) was selected and treated intermittently. Secondly, 54 patients with CR in 2 courses were selected and included in the long-term survival analysis and prognosis analysis. Results: Patients with conventional chemotherapy regimen or combination of dicitabine reduction regimen in the initial induction therapy, 1 course C The CR rate was 32.23% and 65.85% in two courses, 29.27% (24/82) in one course and 60.71% (34/56) in two courses in the traditional chemotherapy group, 38.46% (15/39) in one course and 76.92% (20/26) in two courses in the combined subtractive therapy group. The ratio of primordial cells (P = 0.014) to peripheral blood primordial cells (P = 0.001) at the time of initial diagnosis. No factors affecting the CR rate were found in the patients who had reached CR for two courses (P 0.05). The early mortality rate (within 6 weeks) in the traditional chemotherapy group was 12.20% (10/82) and that in the combination therapy group (within 6 weeks) was 7.69% (3/39). There was no significant difference in adverse reactions between the conventional chemotherapy group and the combination therapy group (P = 0.665). The median survival analysis included 54 patients who had achieved CR in 2 courses and received conventional chemotherapy or combination therapy with the reduction therapy. Follow-up time was 15.0 months (1.3-81.6 months), median survival time was 18.0 months (95% CI: 15.1-20.9), median recurrence-free survival time was 11.0 months (95% CI: 7.9-14.1). One-year OS rate was 62.0%, two-year OS rate was 37.4%. One-year RFS rate was 42.6%, two-year RFS rate was 13.0%. The median survival time in standardized treatment group was 20 months, and median recurrence-free survival time was 8.0%. The median survival time was 18 months and the median non-recurrence survival time was 14 months in the combined subtractive therapy group. Univariate analysis showed that OS was significantly lower in patients with OS (median OS period was 11 months) than in patients with OS (median OS period was 20 months) (P = 0.003); OS was significantly lower in patients with OS (median OS period was 9 months) than in patients with OS (median OS period was 9 months). The OS of 50% patients (median OS period 20 months) (P = 0.005); the OS of 1 course of consolidation therapy after CR (median OS period 4 months) was significantly lower than that of 19 months (median OS period 19 months) after CR (median OS period > 2 courses) (P 0.001), while other factors had no significant effect on OS. In 6 months of RFS, RFS was significantly lower than that in 50% of the patients (median RFS period was 14 months) (P = 0.009); in 5 months of RFS, RFS was significantly lower than that in 50% of the patients (median RFS period was 14 months) (P = 0.009); in 1 course of consolidation therapy after CR, RFS was significantly lower than that in 50% of the patients (median RFS period was 5 months). The RFS of patients (median RFS period 2 months) was significantly lower than that of patients (median RFS period 12 months) (P 0.001) with CR consolidation therapy (> 2 months) and those of secondary AML (median RFS period 0 months) were significantly lower than those of primary AML (median RFS period 11 months) (P 0.001), while other factors had no significant effect on RFS. The independent prognostic factors of OS in ML patients were the ratio of bone marrow primordial cells (P = 0.030), the ratio of peripheral blood primordial cells (P = 0.037) and the consolidation course after reaching CR (P = 0.006); the independent prognostic factors of RFS in elderly AML patients were the ratio of peripheral blood primordial cells (P = 0.023) and the consolidation course after reaching CR (P = 0.001). The rate of CR was 60.71% in the traditional chemotherapy group and 76.92% in the combination and subtraction therapy group. There was no significant difference in the CR rate between the two groups (P 0.05). The median survival time was 18.0 months (95% CI: 15.1-20.9), and the median recurrence-free survival time was 11.0 months (95% CI: 7.9-14.1). One-year OS rate was 62.0%, and two-year OS rate was 37.4%. Multivariate analysis showed that the independent prognostic factors of OS in elderly AML patients were the ratio of bone marrow primordial cells (P = 0.030), the ratio of peripheral blood primordial cells (P = 0.037) and the consolidation course after CR (P = 0.006). The independent prognostic factors of RFS in elderly AML patients were the ratio of peripheral blood primordial cells (P = 0.023) and the number of consolidation courses after reaching CR (P = 0.001).
【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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