伴Ph阳性附加染色体异常慢性髓性白血病的生物学特征及疗效分析  

Analysis of clinical features and prognosis of patients with chronic myelogenous leukemia harboring additional chromosomal abnormalities in Ph-positive cells

作　　者：董晓燕 李玉龙 邬成业 商保军 张琳 程薇 朱尊民 Dong Xiaoyan;Li Yulong;Wu Chengye;Shang Baojun;Zhang Lin;Cheng Wei;Zhu Zunmin(Institute of Hematology,Henan Provincial People's Hospital Henan Key Laboratory of Hematopathology Henan Key Laboratory of Stem Cell Differentiation and Modification,People's Hospital of Zhengzhou University People's Hospital of Henan University,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院血液病研究所,河南省血液病理重点实验室,河南省干细胞分化与调控重点实验室,郑州大学人民医院,河南大学人民医院,郑州450003

出　　处：《中华血液学杂志》2021年第8期660-665,共6页Chinese Journal of Hematology

基　　金：河南省医学科技攻关计划项目(SB20191094)。

摘　　要：目的探讨Ph阳性附加染色体异常(ACA/Ph^(+))对初诊慢性期(CP)和治疗中进展为加速期和急变期慢性髓性白血病(CML-AP/BP)患者生物学特征、疗效和预后的影响。方法回顾性分析2013年1月至2020年6月河南省人民医院收治的410例Ph^(+)CML[初诊CML-CP 348例,治疗中进展为AP/BP(进展期CML)62例]患者的临床资料,根据ELN2020标准将其分为高危、非高危和无ACA/Ph^(+)三组,并比较分析高危/非高危ACA/Ph^(+)对其生物学特征、疗效和预后的影响。结果①348例初诊CML-CP患者,合并ACA/Ph^(+)者20例(5.75%),其中高危ACA/Ph^(+)组3例,非高危ACA/Ph^(+)组17例;无ACA/Ph^(+)组328例。伴ACA/Ph^(+)和无ACA/Ph^(+)组患者的基本临床特征差异无统计学意义(P值均>0.05);非高危ACA/Ph^(+)组和无ACA/Ph^(+)组间完全血液学缓解(CHR)率、完全细胞遗传学反应(CCyR)率、主要分子学反应(MMR)率和5年总生存(OS)率差异均无统计学意义(P值均>0.05);非高危ACA/Ph^(+)组5年无进展生存(PFS)率显著低于无ACA/Ph^(+)组(42.0%对74.5%,χ^(2)=4.766,P=0.029)。②62例进展期CML患者,合并ACA/Ph^(+)者41例(66.13%),其中高危ACA/Ph^(+)组28例,非高危ACA/Ph^(+)组13例;无ACA/Ph^(+)组21例。高危ACA/Ph^(+)组患者中位PLT水平(42.5×10^(9)/L)低于非高危(141×10^(9)/L)和无ACA/Ph^(+)组(109×10^(9)/L)(χ^(2)=4.968,P=0.083);三组间ABL激酶区点突变发生率差异无统计学意义(P=0.652)。高危ACA/Ph^(+)组CCyR率显著低于无ACA/Ph^(+)组(5.3%对46.7%,χ^(2)=5.851,P=0.016)。高危ACA/Ph^(+)组5年OS率为46.2%,非高危ACA/Ph^(+)组为64.3%,无ACA/Ph^(+)组为77.8%,其中高危ACA/Ph^(+)组患者5年OS率明显低于无ACA/Ph^(+)组(χ^(2)=3.878,P=0.049)。亚组分析显示高危Ⅰ组(^(+)8,^(+)Ph或含^(+)8/^(+)Ph的复杂ACA)CML患者的5年OS率为54.5%,与无ACA/Ph^(+)组相比差异无统计学意义(χ^(2)=1.514,P=0.219);高危Ⅱ组[含-7/7q-或i(17q)或含2个及以上高危ACA的复杂核型]为28.6%,显著低于无ACA/Ph^(+)组(χ^(2)=Objective To investigate the effects of additional chromosomal abnormalities(ACA)in Philadelphia chromosome-positive(Ph^(+))cells on biological characteristics,therapy efficacy,and prognosis of patients with primary chronic myeloid leukemia(CML)-chronic phase(CP)and those who developed CML-accelerated phase/blast phase(AP/BP)during therapy.Methods The clinical data of 410 patients with Ph^(+)CML,including 348 patients with primary CML-CP and 62 patients who progressed to CML-AP/BP during treatment,who were admitted to Henan People's Hospital from January 2013 to June 2020 were retrospectively analyzed to categorize into high-risk,non-high-risk,and non-ACA groups according to the ELN2020 criteria.The effects of high-and non-high-risk ACA on biological characteristics,therapy efficacy,and prognosis were compared.Results①Among the 348 patients with primary CML-CP,20 patients(5.75%)had ACA,including 3 and 17 patients with high-risk and non-high-risk ACA,respectively,whereas the remaining 328 patients did not have ACA.There were no significant differences in baseline clinical characteristics between those with and without ACA(P>0.05 for all).The rates of complete hematological response,complete cytogenetic response,major molecular remission,and 5-year overall survival(OS)were not significantly different between the non-high-risk ACA and non-ACA groups(P>0.05 for all);however,the 5-year progression-free survival of the non-high-risk ACA group(42.0%)was significantly lower than that of the non-ACA group(74.5%)(χ^(2)=4.766,P=0.029).②Of the 62 patients who progressed to CML-AP/BP during treatment,41 patients(66.13%)had ACA,including 28 and 13 patients with high-risk and non-high-risk ACA,respectively,whereas the remaining 21 patients did not have ACA.Platelet counts of the high-risk ACA group(42.5×10^(9)/L)were lower than those of the non-high-risk(141×10^(9)/L)and non-ACA groups(109×10^(9)/L)(χ^(2)=4.968,P=0.083).There was no significant difference in the incidence of point mutations in ABL kinase among the thre

关 键 词：附加染色体 白血病 髓性 慢性 BCR-ABL阳性 预后 

分 类 号：R733.72[医药卫生—肿瘤]