摘要
目的:评价尼洛替尼二线与达沙替尼三线对一二线治疗失败的慢性髓性白血病(CML)的疗效,并分析疗效的影响因素。方法:将江苏省昆山市第三人民医院2014年1月-2018年12月伊马替尼一线治疗失败后采用尼洛替尼二线治疗的83例CML患者设为二线治疗组(简称二线组),尼洛替尼二线治疗失败后采用达沙替尼三线治疗的61例CML患者作为三线治疗组(简称三线组);另选伊马替尼一线治疗失败,但由于多种原因,患者在充分告知不更换药物治疗可能发生的严重后果后,仍要求继续伊马替尼治疗的37例CML患者作为对照组。比较各组患者治疗3、6、24个月的血液学、细胞遗传学和分子学反应。应用Logisti C回归分析影响二三线疗效的因素。结果:三组患者治疗3、6、12个月达完全血液学反应(CHR)、主要细胞遗传学反应(MCy R)、主要分子学反应(MMR)率比较差异均有统计学意义(P<0.05)。组间两两比较,二线组治疗3、6、12个月达CHR率分别为100.00%、97.59%、95.18%,高于三线组的90.16%、86.89%、83.61%和对照组的83.78%、75.68%、72.97%;三线组患者治疗6、12个月达CHR率高于对照组。二线组患者治疗3、6、12个月后达MCy R率分别为87.95%、93.98%、93.98%,三线组分别为80.33%、88.52%、86.89%,均高于对照组的67.57%、64.86%、48.65%。二线组患者治疗3、6、12个月达MMR率分别为19.28%、33.72%、60.24%,三线组分别为11.48%、26.23%、49.18%,均高于对照组的0.00%、2.70%、0.00%;二线组治疗12个月达MMR率高于三线组,差异均有统计学意义(P<0.05)。二线组与三线组患者治疗3、6、12个月达MCy R率,3、6个月达MMR率差异无统计学意义(P>0.05)。三组患者主要非血液不良反应中恶心呕吐发生率、血液学不良反应中1~2级贫血发生率差异有统计学意义(P<0.05)。三组的皮疹、眼睑水肿、腹泻、血小板减少、白细胞减少和中性粒细胞减少发生率差异无统计学意义(P>0.05)。组间两两比较,二线组、三线组恶心呕吐、1~2级贫血的发生率高于对照组,差异有统计学意义(P<0.05)。达MMR组与非MMR组Sokal积分、服药依从性、血液学不良反应比较差异有统计学意义(P<0.05)。Logistic回归分析显示,治疗期间减量或停药、3~4级血液学不良反应是影响二、三线疗效的主要因素(OR=22.160,2.715,95%CI=2.795-93.027,1.882-48.834)。结论:尼洛替尼二线与达沙替尼三线对一二线治疗失败的CML患者有较好的疗效。3~4级血液学不良反应、减量或停药是影响二、三线治疗疗效的危险因素。
Objective:To evaluate the efficacy of the second-line nilotinib and third-line dasatinib on chronic myelogenous leukemia(CML) with failed first-and second-line treatments,and analyze the influencing factors of the efficacy.Methods:Selected 83 patients in The Third People’s Hospital of Kunshan City,Jiangsu Province with CML who were treated with nilotinib as the second-line treatment after the failure of the first-line treatment with imatinib as the secondline treatment group(referred to as the second-line group) from January 2014 to December 2018,and 61 CML patients who were treated by dasatinib as the third-line treatment group(referred to as the third-line group) after the failure of the secondline treatment with nilotinib;the first-line treatment with imatinib failed,but due to various reasons,the patients were fully after being informed of the possible serious consequences of not changing the drug treatment,37 CML patients who were still required to continue imatinib treatment served as the control group.The hematological,genetic and molecular responses of each group were compared for 3,6,and 24 months of treatment.LogistiC regression was used to analyze the factors affecting the second and third line curative effects.Results:The three groups had statistically significant differences in the rates of achieving CHR,MCyR,and MMR at 3,6,and 12 months of treatment(P<0.05).Compared the two groups,the CHR rates of the second-line group at 3,6,and 12 months of treatment were 100.00%,97.59%,and 95.18%,respectively;higher than the third-line group’s 90.16%,86.89%,83.61% and the control group’s 83.78%,75.68% and 72.97%;the CHR rate of the third-line group was higher than that of the control group at 6 and 12 months of treatment.The rates of reaching MCyR at 3,6,and 12 months after treatment in the second-line group were 87.95%,93.98% and 93.98%,respectively,while those in the third-line group were 80.33%,88.52% and 86.89%,which were higher than those of the control group of 67.57%,64.86% and 48.65%.The rates of achieving MMR at 3,6,and 12 months of treatment in the second-line group were 19.28%,33.72% and 60.24%,respectively,and those in the third-line group were 11.48%,26.23% and 49.18%,which were higher than those of the control group of 0.00%,2.70% and 0.00%;The rate of reaching MMR within 12 months of treatment in the second-line group was higher than that of the third-line group,and the differences was statistically significant(P<0.05).There was no significant difference in the rate of reaching MCyR between the second-line group and the thirdline group at 3,6,and 12 months,and the rate of reaching MMR at 3 and 6 months(P>0.05).The incidence of nausea and vomiting among the three main non-hematological adverse reactions,and the incidence of grade 1~2 anemia among the hematological adverse reactions were statistically significant(P<0.05).There was no significant difference in the incidence of rash,eyelid edema,diarrhea,thrombocytopenia,leukopenia and neutropenia in the three groups(P>0.05).The incidence of nausea and vomiting and grade 1~2 anemia in the second-line group and the third-line group were higher than that of the control group,and the difference was statistically significant(P<0.05).There were statistically significant differences in Sokal score,medication compliance,and hematological adverse reactions between the MMR group and the non-MMR group(P<0.05).Logistic regression analysis showed that dose reduction or withdrawal during the treatment period,and grade 3~4 hematological adverse reactions were the main factors affecting the second and third line curative effects(OR=22.160,2.715,95% CI=2.795-93.027,1.882-48.834).Conclusion:The second-line nilotinib and the third-line dasatinib have a better effect on CML patients who have failed the first and second-line treatments.Grade 3~4 hematological adverse reactions,dose reduction or withdrawal are risk factors that affect the efficacy of second and third-line treatments.
作者
刘倩
徐静
吴杰
张兴利
邱宏春
LIU Qian;XU Jing;WU Jie;ZHANG Xing-Li;QIU Hong-Chun(Department of Hematology,The Third Peopled Hospital of Kunshan City,Kunsfum 215300,Jiangsu Province,China)
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2022年第1期30-35,共6页
Journal of Experimental Hematology
关键词
尼洛替尼
达沙替尼
二线
三线
慢性髓性白血病
影响因素
Nilotinib
dasatinib
second-line
third-line
chronic myelogenous leukemia
influencing factors
