中大剂量阿糖胞苷巩固治疗细胞遗传学低中危的年轻急性髓系白血病疗效分析

发布时间：2018-02-21 09:24

  本文关键词： 白血病 髓细胞性 急性 阿糖胞苷 巩固治疗 疗效比较性研究　出处：《浙江大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的：探讨中大剂量阿糖胞苷巩固治疗细胞遗传学中低危的年轻急性髓系白血病(60岁),不同单次剂量,不同总累积量及不同疗程数对预后的影响及毒副作用。方法：收集2010年1月至2015年1月期间我院收治的经“DA/IA3+7”等诱导方案治疗,1-2个疗程后达完全缓解的初发AML,筛选出年龄60岁,细胞遗传学低中危,并采用1次及以上中大剂量阿糖胞苷强化巩固化疗的病例142例。对患者身高体重、确诊时血象、外周血异常细胞百分比、染色体、骨髓原始细胞百分比、白血病微小残留病灶等资料进行回顾性分析研究,电话随访了解生存情况。根据患者阿糖胞苷单次剂量,总累积量,化疗疗程数,对患者进行分组,对2年的OS、RFS指标进行评估,并比较化疗期间不良事件。结果：共纳入142例AML患者(60岁=。(1)据单次剂量分组,IDAC-1组(1.0 g/m~2/q12h～1.5 g/m~2/q12h)17例, IDAC-2组(1.6 g/m~2/q12h～1.9 g/m~2/q12h)71例,HDAC组(2.0 g/m~2/q12h～3.0 g/m~2/ql2h)54例。HDAC组在OS上显著优于IDAC-1组(p=0.014),且IDAC-2组与IDAC-1组相比OS也有改善的趋势(p=0.092)。不同单次剂量分组间RFS无统计学差异。COX多因素分析提示单次剂量是OS潜在的危险因素(总P=0.078, IDAC-2 vs IDAC-1:HR 0.566, 95%CI 0.216-1.479, p=0.245; HDAC vs IDAC-1:HR 0.243,95%CI 0.071-0.832,p=0.009)。(2)据总累积量分组,低Ara-C累积组(12 g/m~2)30例,中Ara-C累积组(12g/m~2～36 g/m~2)105例患者,高Ara-C累积组(≥36 g/m~2)7例。中Ara-C累积组在OS上显著优于低Ara-C累积组(p=0.018),高Ara-C累积组与低Ara-C累积组相比,OS有改善的趋势(p=0.076)。不同总累积量分组间RFS无统计学差异。COX多因素分析提示总累积量是OS潜在的危险因素(总P=0.097,中累积量vs低累积量：HR 0.367,95%CI 0.148-0.911, p=0.031;高累积量vs低累积量：p=0.980)。(3)据疗程数分组,1疗程组43例,2疗程组72例,3+4疗程组27例。不同疗程数间OS无统计学差异。3+4疗程组在RFS上显著优于1疗程组(p=0.035)及2疗程组(p=0.037)。COX多因素分析提示疗程数是RFS的潜在危险因素(总P--0.121,1次vs 3+4次：HR 2.695,95%CI 0.747-9.719, p=0.130;2次vs 3+4次：HR 3.559,95% CI 1.052-12.045, p=0.041)。随着Ara-C剂量及疗程数增加,复发率有下降趋势,但观察期内各组间复发率,早期复发率,死亡率无显著性差异。血液学不良反应方面,4次化疗间中性粒细胞缺乏时间无明显差异(P=0.588),各分组间粒缺时间亦无明显差异。结论：对于细胞遗传学低中危的年轻初发急性髓细胞白血病患者(60岁),单次Ara-C化疗剂量1.5 g/m~2/q12h,总Ara-C累积量12 g/m~2能改善患者的OS。化疗疗程数≥3次,可改善患者RFS,并且不同剂量,不同疗程数分组在主要的血液学不良反应方面相似,患者可耐受3疗程及以上的较大剂量的阿糖胞苷化疗。
[Abstract]:Objective: to investigate the effect of medium and high dose cytarabine on the treatment of young acute myeloid leukemia with low and dangerous cytogenetics. Methods: from January 2010 to January 2015, the primary AMLs treated with "DA/IA3 7" and other induction regimens were collected to complete remission, and the age was 60 years. One hundred and forty two patients with moderate and high dose cytarabine reinforcement chemotherapy were enrolled in this study. The height and weight of the patients, the percentage of abnormal peripheral blood cells, the percentage of chromosomes, and the percentage of bone marrow primordial cells were measured. According to the single dose of cytosine arabinoside, the total cumulative dose, the number of chemotherapy courses, the patients were divided into groups to evaluate the 2-year OSN RFS index, according to the single dose of cytarabine, the total cumulative dose, the number of chemotherapy courses, and so on. The adverse events during chemotherapy were compared. Results: a total of 142 patients with AML were divided into two groups according to a single dose: 17 patients in the IDAC-1 group received 1.0 g / mt2q12hmnrm2g / mh, and 17 patients in the IDAC-2 group had 1.6gmmmmmmmm2rq12h 1.9 g / m2q12h 1.9 g / m2q12hwe, 71 patients in the HDAC group received 2.0 gmmmmmm2q2q2hnmnmmmmmmmr2ql2hmmmmmmmmr2ql2hmmmmmmmmr2ql2hm2hmmmmmmmr2ql2hm2gmmmmr2ql2hm2gmmmmr2ql2hdc, respectively. There was no significant difference in RFS between different single dose groups. Cox multivariate analysis showed that single dose was a potential risk factor for OS (total P0. 078, IDAC-2 vs IDAC-1:HR 0. 566, 95 CI 0. 216-1.479, p0. 245; HDAC vs IDAC-1:HR 0. 2439 CI 0. 2439 CI 0. 071-0. 832 CI 0. 009). In the low Ara-C accumulation group, 30 patients were diagnosed as 12g / mng, and in the middle Ara-C accumulation group, there were 236g / mng / mor 2105patients in the middle Ara-C accumulation group. The high Ara-C accumulation group (鈮，

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