摘要目的 观察酪氨酸激酶抑制剂(TKI)治疗后出现Ph细胞染色体异常(chromosomalabnormalities in Ph negative cells,Ph-CA)慢性髓性白血病(CML)患者的临床特征、染色体特点、转归,为临床治疗提供依据.方法 收集并分析2011年9月至2015年7月接受TKI治疗后H出现Ph CA的8例CML患者的临床资料,染色体核型分析采用R显带方法,BCR-AB L融合基因检测采用实时定量PCR方法.结果 8例出现Ph-CA患者中,男6例,女2例,中位年龄51(31～75)岁;Sokal评分低危6例,中危2例.应用伊马替尼出现Ph-CA4例、应用达沙替尼出现1例、应用尼洛替尼出现3例,出现Ph-CA时TKI应用的中位时间为12.0(1.7～34.5)个月;染色体异常以+8最常见,占50.0％,其次为-7(25.0％);Ph-CA出现时8例患者均获得完全血液学反应,但未获得主要分子学反应(MMR);至随访截止,1例患者Ph CA仍持续存在,余7例已消失,持续时间为6.2 (2.5～31.5)个月;Ph-CA消失后1例患者获得MMR,2例获得完全分子学反应,但1例患者再次出现Ph-克隆.结论 伊马替尼、达沙替尼及尼洛替尼治疗CML后均可出现Ph-CA,其中以+8最常见,因此CML患者的细胞遗传学监测十分必要,尽管多数Ph-CA可白行消失,但若出现-7/7q-、复杂核型等,需密切监测.

abstractsObjective To observe the clinical features,characteristics and outcomes of chromosomal abnormalities in Philadelphia negative cells (Ph-CA) of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitor (TKI),and provide the evidence for clinical treatment.Methods We collected and analyzed the clinical and laboratory data of 8 CML patients treated in the affiliated Tumor Hospital of Zhengzhou University from September 2011 to July 2015 and Ph-CA occurred after TKI therapy.Karyotypes and BCR-ABL fusion genes were analyzed by R-banding and real-time quantitative polymerase chain reaction (RT-PCR),respectively.Results 6 cases were male and 2 cases were female,with a median age of 51 (31-75) years old.6 patients had low Sokal risk scores and 2 had intermediate scores.4 cases of Ph-CA occurred with imatinib,1 case with dasatinib and 3 cases with nilotinib.The median duration of Ph-CA appearance was 12.0 (1.7-34.5)months since taking TKI.Chromosomal abnormality +8 was the most common type in Ph-CA,which accounted for 50.0％,followed by-7 (25.0％).When found Ph CA,all patients had complete hematologic response (CHR),but none got main molecular response (MMR).The Ph-CA had gone in 7 cases at the end of follow-up and the median duration was 6.2 (2.5-31.5) months.After Ph-CA disappeared,1 patient obtained MMR and 2 cases achieved complete molecular response (CMR),but Ph+ clone recurred in 1 case.Conclusion Ph CA can be found in CML patients treated with imatinib,dasatinib and nilotinib,and +8 is the most common Ph-CA.So detection of karyotype is significant during treatment.Although most Ph CA can disappear,-7/7q-or other complex karyotypes should be monitored closely.