中高剂量阿糖胞苷巩固治疗急性髓系白血病的临床疗效分析
发布时间：2018-09-14 16:30
【摘要】：目的:本研究采用回顾性的研究方法,观察分析采用中剂量阿糖胞苷(Intermediate-dose Cytarabine,ID-Ara-C)和高剂量阿糖胞苷(High-dose Cytarabine,HD-Ara-C)巩固治疗急性髓系白血病(Acute Myeloid Leukemia,AML)的疗效及安全性,为AML患者探索最佳的巩固治疗方案提供依据。方法:本研究主要以2011年01月至2016年10月期间,于大连医科大学附属第二医院血液内科收治的49例初发AML成人患者为研究对象,按阿糖胞苷剂量由低到高随机分为3组(A、B、C组),其中主要是应用ID-Ara-C(A组1.0g/m2,每12小时静点1次,d1,d3,d5及B组2.0g/m2,每12小时静点1次,d1,d3,d5)或HD-Ara-C(C组3.0g/m2,每12小时静点1次,d1,d3,d5)单用及联合(去甲氧)柔红霉素、依托泊苷、米托蒽醌等一种其它化疗药物,进行巩固强化治疗。其中ID-Ara-C组共连续完成6个周期,联合用药情况两组均相同,HD-Ara-C组为单用阿糖胞苷,共连续完成3个周期。对入选患者每3个月随访一次,持续随访3-5年。期间采集其基本临床资料,观察比较三组患者用药不良事件的发生率、疾病复发率、5年无病生存率及总体生存率等,采用SPSS19.0统计分析软件进行疗效及安全性统计。结果:选取持续完成HD-Ara-C 3个周期,ID-Ara-C 6个周期治疗并可评价疗效的患者44例,其中男性23例,女性21例(男:女=1.09:1),中位年龄53岁(13岁-66岁),其中A组:58岁(15-66岁);B组:54岁(21-64岁);C组:26岁(13-38岁)。A组及B组年龄≥60岁的共11例(25.0%),C组所有患者年龄均小于40岁,无ECOG评分大于1分者,三组患者年龄分布不全相同,C组患者在年龄上与A组、B组均存在差异,且差异有统计学意义(P0.05),A组与B组患者年龄分布差异无统计学意义(P=0.150.05)。疗效:A组:20例中CR率80%,PR率20%,复发5例(25.0%),死亡6例(30.0%),4例为复发后死亡(20.0%),1例为非复发死亡。B组:14例中CR率85.7%,PR率14.3%,复发5例(35.7%),死亡5例(35.7%),其中4例为复发后死亡(28.6%),1例非复发死亡,死因为化疗间期肺内感染。C组:10例患者均获得CR,复发3例(30.0%),复发后死亡1例(10.0%),1例为复发后应用其他方案再次获得缓解并无病生存。三组复发率差异无统计学意义,(A vs.B,P=0.12;B vs.C,P=0.45;A vs.C,P=0.53)。三组均未达到中位OS、DFS,A组:估算3年OS率为66.2%,3年DFS率为65.5%,5年OS率为53.1%,5年DFS率为52.0%。B组:估算3年、5年OS率均为62.1%,3年、5年DFS率56.3%。C组:估算3年及5年OS率为90.0%,3年及5年DFS率为58.2%。三组OS差异无统计学意义,(A vs.B,P=0.64;B vs.C,P=0.16;A vs.C,P=0.31)。三组DFS差异无统计学意义,(A vs.B,P=0.66;B vs.C,P=0.55;A vs.C,P=0.8)。不良反应:三组患者均出现Ⅳ度骨髓抑制,骨髓抑制持续时间差异无统计学意义(P0.05),中性粒细胞缺乏持续中位时间为9-11天。三组患者均出现不同程度的感染,A组感染率为50.5%,B组感染率67.9%,1例因感染死亡。C组感染率80.0%。C组总体感染率高于A组(B vs.A,P=0;C vs.A,P=0.006),B组和C组间感染率无差异(P=0.34)。C组肝功能损伤发生率高于A组(P=0.026),胃肠道反应发生率高于其余两组(A vs.C,P=0.0;B vs.C,P=0.014),A组和B组间非感染不良反应发生率相当(P0.05),三组均无严重心脏、肝脏、肾脏、神经系统功能损伤。结论:本研究中高剂量阿糖胞苷化疗方案应用于年龄40岁AML,虽在疗效上具备一定的优势,较国内外水平有所提高,但不明显,并且存在较大的毒副反应,使其推广受到限制,需要进一步改进。而中剂量阿糖胞苷可应用于部分年龄60岁患者,毒副反应相对低,并且具有同高剂量阿糖胞苷相近的疗效,值得我们探索改进。同时本研究初步探讨了阿糖胞苷1g/m2及2g/m2的疗效差别,发现以2g/m2阿糖胞苷巩固治疗AML的5年生存率高,不良反应较1g/m2无明显差别,初步反应2g/m2阿糖胞苷疗效更佳。但我们仍需扩大病例数,进一步研究阿糖胞苷治疗AML的最佳剂量,同时望探讨根据不同患者的年龄、预后分层、融合基因及疾病状态等情况,详细制定个体化治疗方案,寻找新的疗效好、毒性小化疗药物,以进一步提高患者的疗效及长期生存时间。
[Abstract]:Objective: To observe and analyze the efficacy and safety of mid-dose Cytarabine (ID-Ara-C) and high-dose Cytarabine (HD-Ara-C) in the consolidation of acute myeloid leukemia (AML) by retrospective study, and to explore the best consolidation therapy for AML patients. Methods: From January 2011 to October 2016, 49 adult patients with primary AML were randomly divided into three groups (group A, B, C) according to the dosage of cytarabine, mainly using ID-Ara-C (group A: 1.0g/m2, every 12 hours). One point, d1, d3, d5, and 2.0g/m2 in group B, once every 12 hours, d1, d3, d5, or HD-Ara-C (group C, 3.0g/m2, once every 12 hours, d1, d3, d5) alone or in combination (noroxydaunorubicin, etoposide, mitoxantrone) with one of the other chemotherapeutic agents, were administered intensive consolidation therapy. Patients in HD-Ara-C group were followed up every three months for 3-5 years. The incidence of adverse events, disease recurrence rate, 5-year disease-free survival rate and overall survival rate were observed and compared among the three groups. SPSS 19.0 was used for statistical analysis. Results: 44 patients, including 23 males and 21 females (male: female = 1.09:1), with a median age of 53 years (13-66 years), were enrolled in the study. Group A was 58 years (15-66 years); Group B was 54 years (21-64 years); Group C was 26 years (13-38 years). There were 11 patients (25.0%) in group C, all patients were younger than 40 years old, no ECOG score greater than 1 point. The age distribution of the three groups was not the same. There were significant differences between group C and group A, and between group B and group A (P 0.05). There was no significant difference in age distribution between group A and group B (P = 0.150.05). In group B, CR rate was 85.7%, PR rate was 14.3%, recurrence rate was 35.7%, 5 cases died after recurrence (25.0%), 6 cases died (30.0%), 4 cases died after recurrence (20.0%) and 1 case died of non-recurrence. There was no significant difference in the recurrence rates among the three groups (A vs. B, P = 0.12; B vs. C, P = 0.45; A vs. C, P = 0.53). None of the three groups reached the median OS, DFS, group A: the estimated 3-year OS rate was 66.2%, 3-year DFS rate was 65.5%, and 5-year OS rate was 53.1%. Group B: Estimated 3-year, 5-year OS rates were 62.1%, 3-year, 5-year DFS rates were 56.3%. Group C: Estimated 3-year and 5-year OS rates were 90.0%, 3-year and 5-year DFS rates were 58.2%. There was no significant difference among the three groups of OS (A vs.B, P = 0.64; B vs.C, P = 0.16; A vs.C, P = 0.31). There was no significant difference among the three groups of DFS (A vs.B, P = 0.66; B vs.C, P = 0.55; A. C, P = 0.8; P = 0.8). The median duration of neutrophil deficiency was 9-11 days. The infection rate was 50.5% in group A, 67.9% in group B, and 80.0% in group C. The incidence of liver function injury was higher in group C than in group A (P = 0.026), and the incidence of gastrointestinal reaction was higher in group C than in the other two groups (A vs. C, P = 0.0; B vs. C, P = 0.014). The incidence of non-infectious adverse reactions was similar between group A and B (P 0.05). There was no serious heart, liver, kidney, nerve, spirit in all three groups. CONCLUSION: High dose cytarabine chemotherapy regimen in this study can be applied to AML aged 40 years old, although it has certain advantages in curative effect and has a higher level than that at home and abroad, but it is not obvious, and there are serious toxic and side effects, which restricts its popularization and needs further improvement. At the same time, this study preliminarily explored the difference of the efficacy between cytarabine 1g/m2 and cytarabine 2g/m2. It was found that the 5-year survival rate of AML consolidated with cytarabine 2g/m2 was higher than that of AML consolidated with cytarabine 2g/m2, and the adverse reactions were not significantly different from that of 1g/m2. But we still need to enlarge the number of cases and further study the optimal dosage of cytarabine in the treatment of AML. At the same time, we hope to explore the different age, prognosis stratification, fusion genes and disease status of patients, and to develop a detailed individualized treatment program to find new effective, small toxic chemotherapy drugs for further development. Improve the efficacy and long-term survival of patients.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.71
本文编号：2243255
[Abstract]:Objective: To observe and analyze the efficacy and safety of mid-dose Cytarabine (ID-Ara-C) and high-dose Cytarabine (HD-Ara-C) in the consolidation of acute myeloid leukemia (AML) by retrospective study, and to explore the best consolidation therapy for AML patients. Methods: From January 2011 to October 2016, 49 adult patients with primary AML were randomly divided into three groups (group A, B, C) according to the dosage of cytarabine, mainly using ID-Ara-C (group A: 1.0g/m2, every 12 hours). One point, d1, d3, d5, and 2.0g/m2 in group B, once every 12 hours, d1, d3, d5, or HD-Ara-C (group C, 3.0g/m2, once every 12 hours, d1, d3, d5) alone or in combination (noroxydaunorubicin, etoposide, mitoxantrone) with one of the other chemotherapeutic agents, were administered intensive consolidation therapy. Patients in HD-Ara-C group were followed up every three months for 3-5 years. The incidence of adverse events, disease recurrence rate, 5-year disease-free survival rate and overall survival rate were observed and compared among the three groups. SPSS 19.0 was used for statistical analysis. Results: 44 patients, including 23 males and 21 females (male: female = 1.09:1), with a median age of 53 years (13-66 years), were enrolled in the study. Group A was 58 years (15-66 years); Group B was 54 years (21-64 years); Group C was 26 years (13-38 years). There were 11 patients (25.0%) in group C, all patients were younger than 40 years old, no ECOG score greater than 1 point. The age distribution of the three groups was not the same. There were significant differences between group C and group A, and between group B and group A (P 0.05). There was no significant difference in age distribution between group A and group B (P = 0.150.05). In group B, CR rate was 85.7%, PR rate was 14.3%, recurrence rate was 35.7%, 5 cases died after recurrence (25.0%), 6 cases died (30.0%), 4 cases died after recurrence (20.0%) and 1 case died of non-recurrence. There was no significant difference in the recurrence rates among the three groups (A vs. B, P = 0.12; B vs. C, P = 0.45; A vs. C, P = 0.53). None of the three groups reached the median OS, DFS, group A: the estimated 3-year OS rate was 66.2%, 3-year DFS rate was 65.5%, and 5-year OS rate was 53.1%. Group B: Estimated 3-year, 5-year OS rates were 62.1%, 3-year, 5-year DFS rates were 56.3%. Group C: Estimated 3-year and 5-year OS rates were 90.0%, 3-year and 5-year DFS rates were 58.2%. There was no significant difference among the three groups of OS (A vs.B, P = 0.64; B vs.C, P = 0.16; A vs.C, P = 0.31). There was no significant difference among the three groups of DFS (A vs.B, P = 0.66; B vs.C, P = 0.55; A. C, P = 0.8; P = 0.8). The median duration of neutrophil deficiency was 9-11 days. The infection rate was 50.5% in group A, 67.9% in group B, and 80.0% in group C. The incidence of liver function injury was higher in group C than in group A (P = 0.026), and the incidence of gastrointestinal reaction was higher in group C than in the other two groups (A vs. C, P = 0.0; B vs. C, P = 0.014). The incidence of non-infectious adverse reactions was similar between group A and B (P 0.05). There was no serious heart, liver, kidney, nerve, spirit in all three groups. CONCLUSION: High dose cytarabine chemotherapy regimen in this study can be applied to AML aged 40 years old, although it has certain advantages in curative effect and has a higher level than that at home and abroad, but it is not obvious, and there are serious toxic and side effects, which restricts its popularization and needs further improvement. At the same time, this study preliminarily explored the difference of the efficacy between cytarabine 1g/m2 and cytarabine 2g/m2. It was found that the 5-year survival rate of AML consolidated with cytarabine 2g/m2 was higher than that of AML consolidated with cytarabine 2g/m2, and the adverse reactions were not significantly different from that of 1g/m2. But we still need to enlarge the number of cases and further study the optimal dosage of cytarabine in the treatment of AML. At the same time, we hope to explore the different age, prognosis stratification, fusion genes and disease status of patients, and to develop a detailed individualized treatment program to find new effective, small toxic chemotherapy drugs for further development. Improve the efficacy and long-term survival of patients.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.71
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