二代酪氨酸激酶抑制剂治疗慢性粒细胞白血病的安全性
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摘要
目的探讨二代酪氨酸激酶抑制剂(TKI-Ⅱ)治疗慢性粒细胞白血病(CML)的疗效及安全性。方法选取2013年1月至2018年1月于广州市白云区人民医院进行治疗的CML患者109例作为研究对象,其中服用一代酪氨酸酶抑制剂(TKI-Ⅰ)伊马替尼患者61例,服用TKI-Ⅱ制剂患者共48例,其中达沙替尼患者27例、尼洛替尼患者21例。比较两组患者治疗效果、不良反应发生率。结果 TKI-Ⅱ组患者累积完全血液学缓解(CHR)、主要细胞遗传学缓解(MCyR)、完全细胞遗传学缓解(CCyR)、主要分子学缓解率(MMR)、5年总体生存率(OS)均高于TKI-Ⅰ组,但组间比较差异均无统计学意义(均P>0.05)。TKI-Ⅱ组患者的不良反应包括非血液学不良反应、Ⅲ～Ⅳ级血液学不良反应发生率略低于TKI-Ⅰ组,但组间比较差异均无统计学意义(均P>0.05)。结论 TKI-Ⅱ治疗CML临床疗效显著,可使患者获得相对持久的血液学甚至细胞遗传学缓解效果,延长患者的生存周期,且用药安全性良好,可作为治疗CML的首选药物。
Objective To explore the efficacy and safety of second-generation tyrosine kinase inhibitors(TKI-Ⅱ) in the treatment of chronic myeloid leukemia(CML). Methods A total of 109 patients with CML who were treated in the Baiyun District People's Hospital of Guangzhou from January 2013 to January 2018 were selected as the study subjects. Among them, 61 patients took imatinib,the first-generation tyrosinase inhibitor(TKI-Ⅰ), and 48 patients took TKI-Ⅱ preparations, including 27 patients with Dasatinib and 21 patients with Nilotinib. The therapeutic effect and incidence of adverse reactions were compared between the 2 groups. Results The cumulative complete hematological remission(CHR), major cytogenetic remission(MCyR), complete cytogenetic remission(CCyR),major molecular remission rate(MMR) and 5-year overall survival rate(OS) in the TKI-Ⅱ group were higher than those in the TKI-Ⅰgroup, but there was no significant difference between the 2 groups(P>0.05). The incidence of adverse reactions in the TKI-Ⅱ group including non-hematological adverse reactions and grade Ⅲ-Ⅳ hematological adverse reactions was slightly lower than that in the TKI-Ⅰ group, but there was no significant difference between the 2 groups(P>0.05). Conclusion TKI-Ⅱ is effective in the treatment of CML. It can provide relatively long-lasting effects on hematological and even cytogenetic remission, and prolong the life cycle of patients, and it has good safety. It can be used as the first choice for the treatment of CML.
Objective To explore the efficacy and safety of second-generation tyrosine kinase inhibitors(TKI-Ⅱ) in the treatment of chronic myeloid leukemia(CML). Methods A total of 109 patients with CML who were treated in the Baiyun District People's Hospital of Guangzhou from January 2013 to January 2018 were selected as the study subjects. Among them, 61 patients took imatinib,the first-generation tyrosinase inhibitor(TKI-Ⅰ), and 48 patients took TKI-Ⅱ preparations, including 27 patients with Dasatinib and 21 patients with Nilotinib. The therapeutic effect and incidence of adverse reactions were compared between the 2 groups. Results The cumulative complete hematological remission(CHR), major cytogenetic remission(MCyR), complete cytogenetic remission(CCyR),major molecular remission rate(MMR) and 5-year overall survival rate(OS) in the TKI-Ⅱ group were higher than those in the TKI-Ⅰgroup, but there was no significant difference between the 2 groups(P>0.05). The incidence of adverse reactions in the TKI-Ⅱ group including non-hematological adverse reactions and grade Ⅲ-Ⅳ hematological adverse reactions was slightly lower than that in the TKI-Ⅰ group, but there was no significant difference between the 2 groups(P>0.05). Conclusion TKI-Ⅱ is effective in the treatment of CML. It can provide relatively long-lasting effects on hematological and even cytogenetic remission, and prolong the life cycle of patients, and it has good safety. It can be used as the first choice for the treatment of CML.
引文
[1]马洪霞,陈蕾,焦雪丽,等.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[J].中国实用医药,2016,11(4):118-119.
[2]何思润,秦群,徐文泉.酪氨酸激酶抑制剂治疗慢性粒细胞白血病的不良反应及临床对策[J].中国现代应用药学,2016,33(7):963-966.
[3]扈臣媛,闫志凌,徐开林.慢性粒细胞白血病患者酪氨酸激酶抑制剂的耐药管理[J].国际输血及血液学杂志,2017,40(1):35-40.
[4]Constance C,Trudeau L,Jolicoeur EM,et al.Cardiologist's perspective to the European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia[J].Leukemia,2017,31(3):771-772.
[5]金芳芳,赖斌斌,张莺莺,等.酪氨酸激酶抑制剂在慢性粒细胞白血病慢性期及进展期疗效比较及耐药性分析[J].中国慢性病预防与控制,2018,26(2):146-150.
[6]程雅馨.伊马替尼治疗慢性粒细胞白血病耐药机制及相关药物作用进展[J].医学综述,2016,22(2):313-318.
[7]胡敏,袁凯锋,李晓明,等.伊马替尼、尼洛替尼和达沙替尼对慢性粒细胞白血病慢性期患者的临床疗效[J].中国临床药理学杂志,2016,32(6):511-513.
[8]李青,程辉,游泳,等.慢性粒细胞白血病患者酪氨酸激酶抑制剂停药原因分析[J].白血病·淋巴瘤,2017,26(10):611-613.
[9]曾慧敏,张乐萍.儿童慢性粒细胞白血病临床特点及治疗进展[J].中华临床医师杂志(电子版),2016,10(11):1617-1621.
[10]Sau?ele S,Richter J,Hochhaus A,et al.The concept of treatment-free remission in chronic myeloid leukemia[J].Leukemia,2016,30(8):1638-1647.
[11]黄林,石庆之.老年慢性粒细胞白血病慢性期患者酪氨酸激酶抑制剂治疗进展[J].中国老年学杂志,2016,36(17):4382-4384.
[12]程雅馨.酪氨酸激酶抑制剂在慢性粒细胞性白血病治疗中的应用效果[D].合肥:安徽医科大学,2016.
[13]王媛媛,史春雷,费海荣,等.二代酪氨酸激酶抑制剂治疗慢性粒细胞白血病的近期疗效研究[J].山西医药杂志,2016,45(24):2912-2914.
[14]Hermel DJ,Nael A,Lu YT,et al.Gelatinous bone marrow transformation and emergence of clonal Philadelphia-negative cytogenetic abnormalities with excess blasts in a patient with chronic myeloid leukemia treated with dasatinib[J].Anticancer Drugs,2019,30(4):416-421.
[15]Gugliotta G,Castagnetti F,Breccia M,et al.Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia[J].Am J Hematol,2016,91(6):617-622.
[16]任薇如,吕素娟,任娜娜,等.酪氨酸激酶抑制剂治疗慢性期老年人慢性粒细胞白血病的疗效及安全性分析[J].国际输血及血液学杂志,2016,39(6):471-475.
[17]吕素娟,朱焕玲,李向龙,等.二代酪氨酸激酶抑制剂治疗慢性髓细胞白血病临床疗效分析[J].四川大学学报(医学版),2016,47(2):287-291.
[2]何思润,秦群,徐文泉.酪氨酸激酶抑制剂治疗慢性粒细胞白血病的不良反应及临床对策[J].中国现代应用药学,2016,33(7):963-966.
[3]扈臣媛,闫志凌,徐开林.慢性粒细胞白血病患者酪氨酸激酶抑制剂的耐药管理[J].国际输血及血液学杂志,2017,40(1):35-40.
[4]Constance C,Trudeau L,Jolicoeur EM,et al.Cardiologist's perspective to the European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia[J].Leukemia,2017,31(3):771-772.
[5]金芳芳,赖斌斌,张莺莺,等.酪氨酸激酶抑制剂在慢性粒细胞白血病慢性期及进展期疗效比较及耐药性分析[J].中国慢性病预防与控制,2018,26(2):146-150.
[6]程雅馨.伊马替尼治疗慢性粒细胞白血病耐药机制及相关药物作用进展[J].医学综述,2016,22(2):313-318.
[7]胡敏,袁凯锋,李晓明,等.伊马替尼、尼洛替尼和达沙替尼对慢性粒细胞白血病慢性期患者的临床疗效[J].中国临床药理学杂志,2016,32(6):511-513.
[8]李青,程辉,游泳,等.慢性粒细胞白血病患者酪氨酸激酶抑制剂停药原因分析[J].白血病·淋巴瘤,2017,26(10):611-613.
[9]曾慧敏,张乐萍.儿童慢性粒细胞白血病临床特点及治疗进展[J].中华临床医师杂志(电子版),2016,10(11):1617-1621.
[10]Sau?ele S,Richter J,Hochhaus A,et al.The concept of treatment-free remission in chronic myeloid leukemia[J].Leukemia,2016,30(8):1638-1647.
[11]黄林,石庆之.老年慢性粒细胞白血病慢性期患者酪氨酸激酶抑制剂治疗进展[J].中国老年学杂志,2016,36(17):4382-4384.
[12]程雅馨.酪氨酸激酶抑制剂在慢性粒细胞性白血病治疗中的应用效果[D].合肥:安徽医科大学,2016.
[13]王媛媛,史春雷,费海荣,等.二代酪氨酸激酶抑制剂治疗慢性粒细胞白血病的近期疗效研究[J].山西医药杂志,2016,45(24):2912-2914.
[14]Hermel DJ,Nael A,Lu YT,et al.Gelatinous bone marrow transformation and emergence of clonal Philadelphia-negative cytogenetic abnormalities with excess blasts in a patient with chronic myeloid leukemia treated with dasatinib[J].Anticancer Drugs,2019,30(4):416-421.
[15]Gugliotta G,Castagnetti F,Breccia M,et al.Rotation of nilotinib and imatinib for first-line treatment of chronic phase chronic myeloid leukemia[J].Am J Hematol,2016,91(6):617-622.
[16]任薇如,吕素娟,任娜娜,等.酪氨酸激酶抑制剂治疗慢性期老年人慢性粒细胞白血病的疗效及安全性分析[J].国际输血及血液学杂志,2016,39(6):471-475.
[17]吕素娟,朱焕玲,李向龙,等.二代酪氨酸激酶抑制剂治疗慢性髓细胞白血病临床疗效分析[J].四川大学学报(医学版),2016,47(2):287-291.