中高劑量阿糖胞苷鞏固治療急性髓系白血病的臨床療效分析
發(fā)布時(shí)間：2018-09-14 16:30
【摘要】：目的:本研究采用回顧性的研究方法,觀察分析采用中劑量阿糖胞苷(Intermediate-dose Cytarabine,ID-Ara-C)和高劑量阿糖胞苷(High-dose Cytarabine,HD-Ara-C)鞏固治療急性髓系白血病(Acute Myeloid Leukemia,AML)的療效及安全性,為AML患者探索最佳的鞏固治療方案提供依據(jù)。方法:本研究主要以2011年01月至2016年10月期間,于大連醫(yī)科大學(xué)附屬第二醫(yī)院血液內(nèi)科收治的49例初發(fā)AML成人患者為研究對(duì)象,按阿糖胞苷劑量由低到高隨機(jī)分為3組(A、B、C組),其中主要是應(yīng)用ID-Ara-C(A組1.0g/m2,每12小時(shí)靜點(diǎn)1次,d1,d3,d5及B組2.0g/m2,每12小時(shí)靜點(diǎn)1次,d1,d3,d5)或HD-Ara-C(C組3.0g/m2,每12小時(shí)靜點(diǎn)1次,d1,d3,d5)單用及聯(lián)合(去甲氧)柔紅霉素、依托泊苷、米托蒽醌等一種其它化療藥物,進(jìn)行鞏固強(qiáng)化治療。其中ID-Ara-C組共連續(xù)完成6個(gè)周期,聯(lián)合用藥情況兩組均相同,HD-Ara-C組為單用阿糖胞苷,共連續(xù)完成3個(gè)周期。對(duì)入選患者每3個(gè)月隨訪一次,持續(xù)隨訪3-5年。期間采集其基本臨床資料,觀察比較三組患者用藥不良事件的發(fā)生率、疾病復(fù)發(fā)率、5年無(wú)病生存率及總體生存率等,采用SPSS19.0統(tǒng)計(jì)分析軟件進(jìn)行療效及安全性統(tǒng)計(jì)。結(jié)果:選取持續(xù)完成HD-Ara-C 3個(gè)周期,ID-Ara-C 6個(gè)周期治療并可評(píng)價(jià)療效的患者44例,其中男性23例,女性21例(男:女=1.09:1),中位年齡53歲(13歲-66歲),其中A組:58歲(15-66歲);B組:54歲(21-64歲);C組:26歲(13-38歲)。A組及B組年齡≥60歲的共11例(25.0%),C組所有患者年齡均小于40歲,無(wú)ECOG評(píng)分大于1分者,三組患者年齡分布不全相同,C組患者在年齡上與A組、B組均存在差異,且差異有統(tǒng)計(jì)學(xué)意義(P0.05),A組與B組患者年齡分布差異無(wú)統(tǒng)計(jì)學(xué)意義(P=0.150.05)。療效:A組:20例中CR率80%,PR率20%,復(fù)發(fā)5例(25.0%),死亡6例(30.0%),4例為復(fù)發(fā)后死亡(20.0%),1例為非復(fù)發(fā)死亡。B組:14例中CR率85.7%,PR率14.3%,復(fù)發(fā)5例(35.7%),死亡5例(35.7%),其中4例為復(fù)發(fā)后死亡(28.6%),1例非復(fù)發(fā)死亡,死因?yàn)榛熼g期肺內(nèi)感染。C組:10例患者均獲得CR,復(fù)發(fā)3例(30.0%),復(fù)發(fā)后死亡1例(10.0%),1例為復(fù)發(fā)后應(yīng)用其他方案再次獲得緩解并無(wú)病生存。三組復(fù)發(fā)率差異無(wú)統(tǒng)計(jì)學(xué)意義,(A vs.B,P=0.12;B vs.C,P=0.45;A vs.C,P=0.53)。三組均未達(dá)到中位OS、DFS,A組:估算3年OS率為66.2%,3年DFS率為65.5%,5年OS率為53.1%,5年DFS率為52.0%。B組:估算3年、5年OS率均為62.1%,3年、5年DFS率56.3%。C組:估算3年及5年OS率為90.0%,3年及5年DFS率為58.2%。三組OS差異無(wú)統(tǒng)計(jì)學(xué)意義,(A vs.B,P=0.64;B vs.C,P=0.16;A vs.C,P=0.31)。三組DFS差異無(wú)統(tǒng)計(jì)學(xué)意義,(A vs.B,P=0.66;B vs.C,P=0.55;A vs.C,P=0.8)。不良反應(yīng):三組患者均出現(xiàn)Ⅳ度骨髓抑制,骨髓抑制持續(xù)時(shí)間差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),中性粒細(xì)胞缺乏持續(xù)中位時(shí)間為9-11天。三組患者均出現(xiàn)不同程度的感染,A組感染率為50.5%,B組感染率67.9%,1例因感染死亡。C組感染率80.0%。C組總體感染率高于A組(B vs.A,P=0;C vs.A,P=0.006),B組和C組間感染率無(wú)差異(P=0.34)。C組肝功能損傷發(fā)生率高于A組(P=0.026),胃腸道反應(yīng)發(fā)生率高于其余兩組(A vs.C,P=0.0;B vs.C,P=0.014),A組和B組間非感染不良反應(yīng)發(fā)生率相當(dāng)(P0.05),三組均無(wú)嚴(yán)重心臟、肝臟、腎臟、神經(jīng)系統(tǒng)功能損傷。結(jié)論:本研究中高劑量阿糖胞苷化療方案應(yīng)用于年齡40歲AML,雖在療效上具備一定的優(yōu)勢(shì),較國(guó)內(nèi)外水平有所提高,但不明顯,并且存在較大的毒副反應(yīng),使其推廣受到限制,需要進(jìn)一步改進(jìn)。而中劑量阿糖胞苷可應(yīng)用于部分年齡60歲患者,毒副反應(yīng)相對(duì)低,并且具有同高劑量阿糖胞苷相近的療效,值得我們探索改進(jìn)。同時(shí)本研究初步探討了阿糖胞苷1g/m2及2g/m2的療效差別,發(fā)現(xiàn)以2g/m2阿糖胞苷鞏固治療AML的5年生存率高,不良反應(yīng)較1g/m2無(wú)明顯差別,初步反應(yīng)2g/m2阿糖胞苷療效更佳。但我們?nèi)孕钄U(kuò)大病例數(shù),進(jìn)一步研究阿糖胞苷治療AML的最佳劑量,同時(shí)望探討根據(jù)不同患者的年齡、預(yù)后分層、融合基因及疾病狀態(tài)等情況,詳細(xì)制定個(gè)體化治療方案,尋找新的療效好、毒性小化療藥物,以進(jìn)一步提高患者的療效及長(zhǎng)期生存時(shí)間。
[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.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R733.71
本文編號(hào)：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.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R733.71
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