摘要
目的比较慢性髓性白血病(CML)患者酪氨酸激酶抑制剂(TKI)治疗中细胞遗传学反应和分子学反应的相关性和一致性。方法同期采集419例CML患者的1030对骨髓和外周血标本,以G显带法进行骨髓染色体核型分析,以实时定量PCR法检测外周血BCR.ABL转录本水平。结果全部1030对标本中,骨髓Ph+细胞比例与外周血BCR.ABL水平之间有显著相关性r=O.655,P〈0.01)。不同的细胞遗传学反应所对应的BCR.ABL水平之间差异有统计学意义(P〈0.01)。在完全细胞遗传学反应(CCyR)组中,93.8%的患者国际标准化BCR-ABL转录本水平(BCR-ABLIs)≤1%。在BCR.ABLIS≤0.1%组中,97.5%的患者为CCyR。细胞遗传学反应按未达部分细胞遗传学反应、部分细胞遗传学反应和CCyR分组与分子学反应按BCR.ABL“〉10%、≤10%~〉1%和≤1%分组的一致率为86.2%(1030对中888对)。采集279例CML慢性期患者TKI一线治疗第1年内的497对标本,治疗3个月时主要细胞遗传学反应与BCR.ABL“≤10%、治疗6和12个月时CCyR与BCR.ABL“≤l%的一致率分别为89.0%、83.5%和92.1%。结论CML患者在TKI治疗中,细胞遗传学反应和分子学反应具有显著的相关性和较高的一致性,但采用细胞遗传学和分子学分析评估早期疗效时存在一定的差异。
Objective Compare the correlation and the concordance of simultaneous bone marrow cytogenetic and peripheral blood molecular responses in patients with chronic myeloid leukemia (CML) during tyrosine kinase inhibitor (TKI) treatment. Methods A total of 1 030 pairs of simultaneous bone marrow and peripheral blood samples from 419 patients with CML during TKI treatment were analyzed with standard G-banding techniques and real-time quantitative reverse transcriptase PCR (Q-PCR). Results The Spearman correlation coefficient for the paired analysis of the percentage of Ph-positive metaphases versus Q-PCR (BCR-ABL/ABL) values was 0.655 (n=l 030, P〈0.01 ). There was a significant difference in terms of BCR-ABL values among all three cytogenetic response groups of no partial cytogenetic (no PCyR), partial cytogenetic (PCyR) and complete cytogenetic responses (CCyR) (P〈 0.01 ). 93.8% of the patients in CCyR had BCR-ABLIS.[International Scale (IS)], and 97.5% of those with BCR-ABL〈0.1% (IS) were in CCyR. There was good concordance of 86.2% ( 888 of 1030 samples) when BCR-ABL values according to cutoffs of BCR-ABL〉10% (IS), 〈10%-〉1% (IS) and 〈1% (IS) were coupled with cytogenetic responses including no PCyR, PCyR and CCyR. Furthermore, 497 pairs of samples from 279 patients with newly diagnosed CML in chronic phase during the first year on TKI as first- line therapy were analyzed. Concordances between major cytogenetic response and BCR-ABL〈I 0% (IS) at 3 months, CCyR and BCR-ABL〈1% (IS) at 6 months and 12 months were 89%, 83.5% and 92.1%, respectively. Conclusions There were significant correlation and concordance between cytogenetic and molecular responses, and some differences in assessment of early responses between using cytogenetic and molecular analyses in CML patients during TKI treatment.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2014年第2期104-108,共5页
Chinese Journal of Hematology
基金
北京市科学技术委员会基金(z131100004013026)
北京大学人民医院研究与发展基金(RDC2012-20)