酪氨酸激酶抑制剂治疗慢性粒细胞白血病的临床疗效分析

Efficacy of Tyrosine Kinase Inhibitor in Treatment of Chronic Myeloid Leukemia Patients

目的回顾性分析酪氨酸激酶抑制剂(TKI)治疗慢性粒细胞白血病(CML)的临床疗效。方法对近十年来在我院门诊接受治疗的655例CML患者的临床资料及随访结果进行回顾性分析。其中551例患者为慢性期,62例为加速期,42例为急变期。83例患者仅接受了干扰素治疗,572例接受了伊马替尼(慢性期400mg/d,加速/急变期600mg/d)。治疗期间定期监测患者血液学、细胞及分子遗传学反应,参照2011年版CML指南评价治疗反应及疗效,采用Kaplan-Meier曲线进行生存分析。结果随访结束时总完全血液学缓解(CHR)、主要细胞遗传学缓解(MCyR)、完全细胞遗传学缓解(CCyR)和主要分子生物学缓解(MMR)率分别为92.1%、75.8%、73.1%和47.9%。所有患者总体1年、3年、5年和10年总生存(OS)率为(96.3±0.8)%、(86.3±1.8)%、(79.0±2.4)%和(66.5±4.8)%,1年、3年、5年和10年无事件生存(EFS)率为(92.2±1.1)%、(77.9±2.1)%、(67.9±6.8)%和(35.8±6.0)%,慢性期患者累积获得CHR、MCyR、CCyR和MMR的比例分别达到98.7%、82.5%、79.4%和52.4%。加速期和急变期患者,其疗效显著降低。早慢性期疗效好于晚慢性期,尽早开始TKI治疗能使患者明显获益,早期分子学反应预示更好的远期疗效,伊马替尼耐药的患者换用二代TKI后,随访结束时MCyR率为43.5%,MMR率为25.5%。结论慢性期CML患者接受TKI治疗的疗效及预后较好,且越早用药,疗效和预后也越好。

Objective To evaluate the effects of tyrosine kinase inhibitors（TKI）in the treatment of chronic myeloid leukemia.Methods There were total 655cases of chronic myeloid leukemia treated in one single-institution enrolled in this study.The dosage of TKI Imatinib was 400mg/d for chronic phase,600mg/d for accelerated and blast phase respectively.Complete blood count,cytogenetic and molecular studies were regularly monitored during the course of therapy.The therapeutic effect was evaluated and the survival analysis was performed.Results The total complete hematologic response（CHR）,major cytogenetic response（MCyR）,complete cytogenetic response（CCyR）and major molecular response（MMR）rates were 92.1%,75.8%,73.1% and 47.9% respectively.1-year,3-year,5-year and 10-year overall survival（OS）rates were（96.3±0.8）%,（86.3±1.8）%,（79.0±2.4）%and（66.5±4.8）%respectively.1year,3-year,5-year and 10-year event-free survival（EFS）rates were（92.2±1.1）%,（77.9±2.1）%,（67.9±6.8）%and（35.8±6.0）%respectively.The proportion of the patients in chronic phase achieving CHR,MCyR,CCyR and MMR were 98.7%,82.5%,79.4%and 52.4%respectivly.Compared with chronic phase patients,the efficacy of IM in the treatment of accelerated phase and blast phase patients was significantly lower.The effect of TKI in early chronic phase was better than that in late chronic phase.Early molecular response was associated with a better 5-year EFS,but not OS.Conclusion CML patients in chronic phase treated with TKI have a better outcome.The earlier TKI be used,the better the prognosis and efficacy be achieved.