甲磺酸伊马替尼治疗慢性粒细胞白血病慢性期100例追踪观察  

Efficacy and safety evaluation of imatinib mesylate for chronic granulocytic leukemia patients in chronic phase: a 4.5-year follow-up of 100 cases

作　　者：江倩[1] 陈珊珊[1] 江滨[1] 江浩[1] 丘镜滢[1] 刘艳荣[1] 张艳[1] 秦亚溱[1] 陆颖[1] 黄晓军[1] 陆道培[1] 

机构地区：[1]北京大学人民医院 血液病研究所,100044

出　　处：《中华血液学杂志》2006年第11期721-726,共6页Chinese Journal of Hematology

摘　　要：目的评价甲磺酸伊马替尼治疗Ph阳性(Ph+)慢性粒细胞白血病(CML)慢性期的有效性与安全性。方法100例Ph+CML第1次慢性期(多为干扰素α治疗失败的晚慢性期)患者持续口服甲磺酸伊马替尼400 mg／d(93例)或600 mg／d(7例)。结果中位追踪49．0(4．5～58．0)个月,累积获得的完全血液学缓解率为100％,主要细胞遗传学缓解(MCyR)率为86．0％,完全细胞遗传学缓解(CCyR)率为76．0％,CCyR患者中主要分子学缓解率为68．8％,完全分子学缓解率为26．6％,预计54个月无疾病进展率和总生存率分别为90．0％和92．6％。治疗中,18．0％和28．0％的患者分别出现了Ⅲ级白细胞和血小板减少。多因素分析显示,年龄≥60岁(P=0．033,RR=4．196)和治疗前外周血中嗜碱粒细胞比例≥0．05(P=0．012,RR=4．173)为独立预示Ⅲ级白细胞减少发生的危险因素。非血液学毒性发生普遍,大多程度轻微。10．0％和13．0％的患者分别检出了Ph+和Ph-细胞克隆演变,除个别Ph+细胞克隆演变者外多数处于疾病稳定状态。多因素分析显示,治疗前骨髓中存在高比例(100％)的Ph+细胞(P=0．027,RR=0．523或P=0．004,RR=0．424)和治疗中出现Ⅲ级白细胞减少(P=0．001,RR=0．306或P=0．004,RR=0．337)为独立影响MCyR或CCyR获得时间和比例的不利因素。结论甲磺酸伊马替尼明显提高Ph+CML慢性期患者的细胞遗传学和分子学疗效,改善生活质量,延长无疾病进展生存期。Objective To evaluate the efficacy and safety of imatinib mesylate （imatinib） in patients with Philadelphia chromosome-positive （Ph-positive） chronic granulocytic leukemia （CGL） in chronic phase. Methods One-hundred patients with Ph-positive CGL in the first chronic phase （ most patients were in late chronic phase after failure in interferon-α therapy） were treated with imatinib 400 mg （n = 93 ） or 600 mg （ n = 7） once daily. Results With a median follow-up of 49 （ range 4.5 -58.0 ） months, cumulative complete hematological response （CHR） rate was 100%, major cytogenetic response （MCyR） rate 86.0% and complete cytogenetic response （CCyR） rate 76.0%. Among patients with CCyR, cumulative major molecular response （MMoR） rate 68.8% and complete molecular response （CMoR） rate 26.6%. The estimated 54- month progression-free survival rate was 90.0% , and overall survival rate 92.6%. Grade 3 leukocytopenia occurred in 18.8% of the patients, and grade 3 thrombocytopenia in 28.0% during therapy. Multivariate analysis for severe hematological toxicities revealed that age over 60 years （P = 0. 033, RR = 4. 196 ） and peripheral basophils≥5% （P = 0. 012, RR = 4. 173 ） before therapy were independent predictive factors for grade 3 leukocytopenia. Nonhematological toxicities were common and tolerable. Clonal evolution Ph-positive cell and Ph-negative cell emerged in 10.0% and 13.0% of the patients, respectively. So far, all patients with Ph-negative cell clonal evolution remained in CHR. Multivariate analysis for MCyR or CCyR showed that high percentage （ 100% ） of marrow Ph-positive cells before therapy （ P = 0. 027, RR = 0.523 or P = 0. 004, RR = 0. 424 ） and occurrence of grade 3 leukocytopenia during therapy （ P = 0. 001, RR = 0. 306 or P = 0. 004, RR = 0. 337 ） were risk factors for suboptimal responses. Conclusions Imatinib significantly improves eytogenetie and molecular response rates, quality of life, and progression-free survival for patients with P

关 键 词：白血病 髓样 慢性 费城染色体 伊马替尼 

分 类 号：R733.7[医药卫生—肿瘤]