CML慢性期伴附加染色体异常患者TKI疗效分析

TKI efficacy in CML patients with additional chromosomal abnormality

目的探讨细胞遗传学特征对慢性粒细胞白血病(CML)初诊患者用药的指导意义。方法收集2018年1月-2021年12月初诊的93例CML慢性期患者的临床资料、R显带染色体核型分析结果,根据有无附加染色体核型异常分为典型易位组及附加染色体异常组,回顾性分析经酪氨酸激酶抑制剂(TKI)治疗后血液学疗效和分子生物学疗效。结果93例CML患者BCR-ABL基因阳性率为100%,常规染色体核型R显带阳性检出率为100%,其中典型Ph染色体t(9;22)(q34;q11)易位占比87.1%,伴有+8、-Y等附加染色体异常核型占比12.9%,治疗后均实现完全血液学缓解。与典型易位组相比,附加染色体异常组BCR-ABLIS达标比例差异无统计学意义(P分别为0.047,0.040)。但在典型易位组中,经尼罗替尼治疗后分子达标比例3、6、12个月显著高于伊马替尼,主要分子反应也显著增高。附加染色体异常组中,尼罗替尼治疗后分子达标比例3、6、12个月显著高于伊马替尼,主要分子反应也显著高于伊马替尼,但均未达到深度分子生物学缓解,差异有统计学意义(P分别为0.003,0.006)。结论伴附加染色体异常初诊CML慢性期患者使用二代TKI分子达标率更高,细胞遗传学特征对CML慢性期患者治疗策略选择有指导意义。

Objective To explore the significance of cytogenetic characteristics in dictating treatment for patients with initial chronic myelocytic leukemia(CML) diagnosis. Methods The clinical data, R dominant band karyotype analysis results of 93 patients with chronic phase CML diagnosed from January, 2018 to December,2021 were collected and divided into the typical ectopic group and the additional chromosomal abnormality group according to the presence or absence of additional karyotype abnormality, and the hematological efficacy and molecular biological efficacy after treatment with tyrosine kinase inhibitors(TKI) were retrospectively analyzed. Results 93 patients with primary CML had 100% BCR-ABL gene positivity, and 100% of conventional chromosomal karyotype R apparent generation positivity, of which 87.1% had the typical Ph chromosome t(9;22)(q34;q11) translocation and 12.9% had additional chromosomal abnormal karyotypes such as +8 and-Y. All patients achieved complete hematologic response after TKI therapy. There was no statistical difference in the proportion of BCR-ABLISattainment in the additional chromosomal abnormality group compared with the typical ectopic group(P=0.047, 0.040). However, in the typical ectopic group, the molecular attainment rates were significantly higher with nilotinib at 3, 6, and 12 months than with imatinib, and the major molecular response was also significantly increased. In the additional chromosomal abnormality group, the percentage of molecular attainment after nilotinib treatment was significantly higher at 3, 6 and 12months than with imatinib, and the major molecular response was also significantly higher than imatinib, but none of them achieved the MR4.0 and MR4.5, with statistically significant differences in the results(P =0.003, 0.006). Conclusion Patients with additional chromosomes abnormality have a higher molecule response with second-generation TKI, and cytogenetic features are instructive in the choice of treatment strategy for patients with chronic phase of CML.