费城染色体阴性细胞出现克隆性染色体异常对慢性髓性白血病疗效影响的临床观察

The influence of additive clonal chromosome abnormalities in Ph negative cells on the efficacy of chronic myeloid leukemia

目的探讨酪氨酸激酶抑制剂(TKI)治疗期间费城染色体阴性细胞出现克隆性染色体异常(CCA/Ph^-)对慢性髓性白血病(CML)治疗疗效的影响。方法回顾性分析河南省肿瘤医院2014年7月至2017年12月检出CCA/Ph^-的28例CML患者的临床资料。单因素分析采用Kaplan-Meier法,多因素分析采用Cox比例风险模型法。结果纳入28例CML患者,男17例,女11例,首次检出CCA/Ph^-时患者的中位年龄为42.5岁。CCA/Ph^-以+8为主异常最常见,占60.7%,7号染色体为主异常占14.3%。64.3%的CCA/Ph^-呈一过性出现,35.7%为反复出现(出现次数≥2次)。42.9%患者血象呈二系或三系减低。89.3%患者获主要细胞遗传学反应(MCyR),25.0%患者获主要分子学反应(MMR)。中位随访26.5个月。至随访结束,32.1%患者TKI治疗失败,中位无失败治疗时间为8(1~41)月。单因素分析显示:CCA/Ph^-出现频率、CCA/Ph^-出现时血象是否正常等因素与治疗失败有关联(P值均<0.05);CCA/Ph^-出现时血象是否正常与MMR率有关联(P<0.05)。多因素分析显示:CCA/Ph^-出现时血象两系或三系减低是影响MMR率的独立危险因素(RR=3.868,95%CI 1.216~12.298,P=0.022),但对治疗失败率的影响不显著。结论TKI治疗期间CCA/Ph^-出现时伴血象两系或三系减低是影响CML患者MMR率的独立危险因素。CCA/Ph^-反复出现者的治疗失败率较CCA/Ph^-一过性出现者显著升高。TKI治疗期间出现CCA/Ph^-时血象减低者是否需要停药、减量或更换其他TKI治疗,应结合CML治疗反应和ABL激酶区突变综合评估。

Objective To investigate the influence of additional clonal chromosome abnormalities in Ph negative cells(CCA/Ph^-)on the efficacy of chronic myeloid leukemia(CML)after tyrosine kinase inhibitors(TKI)treatment.Methods The clinical data of 28 CML patients with CCA/Ph^- treated in Henan Cancer Hospital from July 2014 to December 2017 were analyzed retrospectively.The univariate analysis was carried out by Kaplan-Meier method.Multivariate analysis was done by Cox proportional risk model.Results A total of 28 CCA/Ph^- patients were recruited including 17 males and 11 females with median age of 42.5 years old.The most common CCA/Ph^- were trisomy 8(60.7%),monosomy 7(14.3%).64.3%CCA/Ph^- were transient and 35.7% recurrent(more than 2 times).Cytopenia in two or three lineages of peripheral blood was seen in 42.9% patients.As to the efficacy,89.3% patients achieved major cytogenetic response(MCyR),25%with major molecular response(MMR).The median follow-up time was 26.5 months.Treatment failure(TF)of TKI occurred in 32.1%patients with median duration of response 8(1-41)months.Univariate analysis showed that TF rate was significantly correlated with the frequency of CCA/Ph^- and cytopenia(all P<0.05).The MMR rate was also significantly correlated with cytopenia(P<0.05).Cytopenia of two lineages or pancytopenia was an independent risk factor related to MMR rate(RR=3.868,95%CI 1.216-12.298,P=0.022).Conclusions Cytopenia in CCA/Ph^- appears to be an independent risk factor of MMR in CML patients with TKI treatment.The recurrent CCA/Ph^- may link to higher treatment failure rate.Drug withdrawal or alternative strategy should be considered according to response and the ABL kinase mutations.