附加染色体异常对慢性髓系白血病慢性期患者酪氨酸激酶抑制剂疗效的影响

Effect of Additional Chromosomal Abnormalities on the Outcome of CML-CP Patients Receiving TKI Therapy

目的:探讨附加染色体异常对酪氨酸激酶抑制剂伊马替尼治疗慢性髓系白血病慢性期(CML-CP)患者效果及预后的影响。方法:利用Graphpad 6. 0软件,采用Kaplan-Meier法、Long-rank检验和x^2检验等方法,比较苏州大学附属第一医院2009年5月至2014年10月589例(根据核型异常分为5组) CML-CP接受伊马替尼治疗的患者服用伊马替尼3、6、12个月时BCR-ABL1^(IS)达标的水平、累积主要分子学缓解(MMR)、累积完全细胞遗传学缓解(CCyR)、无进展生存(PFS)、无事件生存(EFS)、总体生存(OS)的差异。结果:与单纯t(9; 22)组相比,伴有附加染色体异常组3个月和6个月BCR-ABL1^(IS)达标的比例均偏低,2组间差异有统计学意义[50%(12/24) vs73. 94%(261/353),P <0. 05; 50%(10/20) vs 72. 05%(232/322)(P <0. 05)];与单纯t(9; 22)组相比,变异型易位组仅6个月BCR-ABL1^(IS)达标的比例偏低,2组间差异有统计学意义[53. 3%(16/30) vs 72. 05%(232/322)(P <0. 05)]。伴有附加染色体异常组与其他4组比较,伴有附加染色体异常组4年的累积CCyR率和EFS率均最低,差异有统计学意义(P <0. 05,P <0. 01)。两两比较仅伴有附加染色体异常组与单纯t(9; 22)组在累积CCyR和EFS水平上差异有统计学意义(47. 25%vs 84. 01%,P <0. 05; 75. 03%vs 90. 01%)(P <0. 01)。结论:附加染色体异常影响CML-CP患者TKI治疗的效果,该类患者治疗效果欠佳,预后较差。

Objectives:Toexplorethe effect of additionalchromosomal abnormalities onthe prognosisand outcome of CML-CP patients receiving imatinib therapy.Methods:The clinical and genetic data of 589 CML-CPpatients receiving imatinibtreatment between May 2009 and October 2014 in the 1 st Affiliated Hospital of Soochow University were analyzed,the 589patientsweredivided into 5groups according to thekaryotypesat theinitial diagnosis.The OS(overall survival),PFS(progression-free survival),EFS(event-free survival),Cumulative MMR(major molecular remission)and Cumulative CCyR(complete cytogenetic remission)were calculated by using the Kaplan-TMeier method andcomparedby using the log-rank text by Graphpad 6.0.The p2 test was used to compare the frequency of optimal molecular response at 3,6,12 months among the 5 groups.Results:There was significant difference about the frequency ofoptimal molecularresponseat 3and6monthsbetween CML-CPpatientswithadditionalchromosomal abnormalities andthosewithclassict(9;22)[50%(12/24)vs73.94%(261/353),P<0.05;50%(10/20)vs 72.05%(232^322)(P<0.05)],andthesame significantdifference wasfoundat 6monthsbetween thegroupwith variant translocationsandthat withclassict(9;22)[53.3%(16/30)vs 72.05%(232/322)(P<0.05)].TheP values ofcumulativeCCyR(P<0.05)andEFS(P<0.01)for 4yeas were statisticallysignificantbetween CML-CP patients with additional chromosomal abnormalities and the other 4 groups.Compared one to another,there was the significant difference in cumulative CCyRand EFS for 4 years between CML-CP patients with additional chromosomal abnormalities and those with classic t(9;22)(47.25%84.01%)(P<0.05);(77.03%^90.01%)(P<0.01).Conclusion:The additional chromosomal abnormalities influence the outcome of CML-CP patients receiving imatinib treatment,which make poor prognosis.