TKI治疗慢性髓系白血病的疗效及获得深层分子反应的相关影响因素分析

Analysis of Efficacy and Related Factors of Acquired Deep Molecular Response in Chronic Myeloid Leukemia Patients Treated with TKI

目的:评价酪氨酸激酶抑制剂(TKI)治疗慢性髓系白血病(CML)的疗效,探讨获得深层分子反应(DMR)的影响因素。方法:对我院接受TKI治疗的131例成人CML患者的临床资料及随访结果进行了分析,评价各时间点治疗反应的疗效,分析影响获得MR^(4.5)的相关因素。结果:131例患者中位随访24(6-120)个月,其中30例在中位伊马替尼治疗12(1-69.6)个月换为尼洛替尼治疗,13例在中位伊马替尼治疗31.2(3.1-87.6)个月时换达沙替尼。治疗3、6及12个月的获得主要细胞遗传学反应(MCyR)率分别为78%、79.4%及95.9%,获得完全细胞遗传学反应(CCyR)率分别为48.8%、66.7%及73.5%。60%的患者3个月时BCR-ABL^(IS)<10%,6个月BCR-ABL^(IS)<1%占56.3%,12个月BCR-ABL^(IS)<0.1%达55.2%。持续伊马替尼治疗组中53例(60.9%)获得MR^(4.5),31例(35.6%)能够获得稳定的MR^(4.5)。多因素分析显示,性别、诊断时WBC计数及3个月BCR-ABL^(IS)水平是获得MR^(4.5)的独立影响因素,3个月BCR-ABL^(IS)水平是获得稳定MR^(4.5)的独立影响因素。换第二代TKI组中18例(40.9%)获得MR^(4.5),3个月BCR-ABL^(IS)水平同样是获得MR^(4.5)的独立影响因素。结论:伊马替尼治疗新诊断CML患者获得细胞遗传学与分子学疗效优异,对于耐药或不能耐受患者换为第二代TKI同样能够获得满意的疗效且DMR率更高,获得早期分子反应预测MR^(4.5)和稳定的MR^(4.5)的累积发生率更高。

Objective： To evaluate the efficacy and related factors of acquired deep molecular response（ DMR） for treating patients with chronic myeloid leukemia（ CML） by using TKI. Methods： The clinical data of 131 TKI-treated patients with CML were analyzed retrospectively. The therapeutic effects of each time-points were evaluated,and the related factors of MR^4.5 were analyzed. Results： The median follow up-time of 131 cases with CML was 24 months（ 6-120 months）,among them the treatment of 30 patient was converted to nilotinib after a median of 12 months（ 1-69. 6 months） with imatinib,and 13 patient was converted to dasatinib treatment after a median of 31. 2 month（ 3.1-87. 6 months） with imatinib. After treatment for 3,6 and 12 month,the rate of major cytogenetic response（ MCyR） was 78%,79. 4% and 95. 9%,and the complete cytogenetic response（ CCyR） rate was 48. 8%,66. 7% and 73. 5%, respectively. 60% patients obtained BCR-ABL^IS 〈10% at 3 months,56. 3% patients obtained BCRABL^IS 〈1% at 6 months,55. 2% patients obtained BCR-ABL^IS〈 0. 1% at 12 months. In continued imatinib therapy group,53 patients（ 60. 9%） obtained MR^4.5,and 33 cases（ 37. 9%） obtained stable MR^4.5. Multivariate analysis showed that sex,WBC count at the time of diagnosis and BCR-ABL^IS level at 3 months were independent factors for obtaining MR^4.5.The 3-month BCR-ABL^IS level was an independent factor to obtain stable MR^4.5. 18 cases（ 40. 9%） in the second-generation TKI group received MR^4.5 and the 3-month BCR-ABL^IS level was also an independent predictor for MR^4.5. Conclusion：The excellent cytogenetic and molecular responses are observed in CML patients treated with cmatinib. Conversion to secondgeneration TKI therapy for patients with resistant or intolerant to imatinib also can achieve a satisfactory responseand a higher rate of deeper molecular remission. The higher incidence of early molecular response predicting MR^4.5 and stable MR^4.5 is achieved.