慢性髓性白血病患者酪氨酸激酶抑制剂治疗3个月分子反应的预后价值
Predictive value of molecular response after treatment with tyrosine kinase inhibitor for 3 months in patients with chronic myeloid leukemia
摘要目的 了解慢性髓性白血病(CML)患者酪氨酸激酶抑制剂(TKI)治疗早期BCR-ABL转录本水平检测的预后价值,为CML患者进行早期预后评估和治疗选择提供依据.方法 通过实时定量PCR方法检测53例CML患者TKI治疗前后不同时间BCR-ABL转录本的水平,分析治疗3个月时BCR-ABL水平与之后获得的分子反应、疾病进展以及突变情况的关系.结果 30例初诊CML患者外周血BCR-ABL转录本水平中位值为43.99%,作为分子反应评价的基线.TKI治疗3个月BCR-ABLmRNA≤4.40%(降低超过1个对数级)31例(58.49%)患者,>4.40%(降低小于1个对数级)者22例(41.51%),前者治疗18个月获得主要分子学反应(MMR)的比例明显高于后者(90.32%对18.18%,P=0.000);36个月累积完全分子学反应(CMR)的比例前者也明显高于后者(48.39%对0,P=0.000).治疗3个月BCR-ABL水平越低获得MMR越早,但BCR-ABL mRNA>4.40%组检测到BCR-ABL激酶区突变患者的比例明显高于BCR-ABL mRNA≤4.40%组(22.73%比0,P=0.021),虽然患者疾病进展的比例有增高的趋势,但差异无统计学意义(P=0.052).结论 TKI治疗3个月时BCR-ABL转录本水平对患者的预后评估有重要价值,可能有助于早期优化CML患者的治疗,提高患者的疗效.
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abstractsObjective To understand the predictive value of early monitoring BCR-ABL transcripts in patients with chronic myeloid leukemia (CML) after treatment with tyrosine kinase inhibitor (TKI),and to provides the information for early assessment of prognosis and treatment options.Methods BCR-ABL transcripts of 53 CML patients before and after TKI treatment were detected by using real-time quantitative RT-PCR.The relationship between BCR-ABL transcripts level after TKI treatment for 3 months and the later molecular response,progression and mutation was analyzed.Results The median values of BCR-ABL transcripts in peripheral blood samples from 30 newly diagnosed patients were 43.99%,which was used as a baseline of BCR-ABL transcripts for molecular response evaluation.Of 53 patients,31 (58.49%) had a BCR-ABL mRNA ≤4.40% (reduced more than 1 log) and 22 (41.51%) greater than 4.40% (reduced to less than 1 log) after 3 months of TKI treatment.The former 31 patients had a significantly higher 18-months cumulative incidence of major molecular response (MMR) (90.32%vs 18.18%,P=0.000) and 3-year cumulative incidence of complete molecular response (CMR) (48.39% vs 0,P=0.000) compared with the latter 22 patients.The lower BCR-ABL level was,the earlier MMR reached.The proportion of patients with a mutation in group of BCR-ABL mRNA >4.40% was significantly higher than that of BCR-ABL mRNA ≤4.40% (22.73% vs 0,P=0.021).The incidence of progression increased in group of BCR-ABL mRNA >4.40%,but the difference was not statistically significant (P=0.052).Conclusions It is important for the prognosis evaluation of the patients to monitor the level of BCR-ABL transcripts at 3 months after TKI treatment,which might help to early optimization of treatment and to improve curative effect of CML patients.
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