Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia.
Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia.
复制标题
酪氨酸激酶抑制剂治疗1个月后，BCR-ABL1早期的转录本作为慢性髓样白血病的治疗反应指标。
DOI：
10.1371/journal.pone.0171041
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Mustjoki S
中科院分区：
文献类型：
--
作者：
El Missiry M;Hjorth-Hansen H;Richter J;Olson-Strömberg U;Stenke L;Porkka K;Kreutzman A;Mustjoki S
在慢性粒细胞白血病(CML)中，早期治疗预测对于识别总体预后较差的患者非常重要。我们研究了用酪氨酸激酶抑制剂(TKI)治疗1个月后bcr-abl1转录水平降低来预测治疗反应的可行性。纳入52例接受TKI治疗的一线CML患者(伊马替尼26例，达沙替尼21例，尼洛替尼5例)，分别在诊断(Dg)、1、3、6、12、18、24和36个月检测bcr-abl1转录水平。1个月时bcr-abl1转录本与初始bcr-abl1转录本水平相比的倍数变化被用来指示早期治疗反应。在我们的队列中，21%的患者在1个月后bcr-abl1转录水平没有下降，被归类为反应差。令人惊讶的是，这些患者在dg时bcr-abl1转录水平低于应答者(31%比48%，p=0.0083)。反应差的患者更容易出现脾肿大(55%比15%；p<；0.01)和骨髓中Ph+CD34+CD38-细胞的比例更高(91%比75%，p<；0.05)。应答差的患者主要分子应答率较低(12M18%比%，P<；0.01；18M27%比75%，P<；0.01；24M55%比87%，P<；0.01)。总而言之，早期治疗反应分析定义了一个生物学上不同的长期结果较差的患者亚组。
In chronic myeloid leukemia (CML), early treatment prediction is important to identify patients with inferior overall outcomes. We examined the feasibility of using reductions in BCR-ABL1 transcript levels after 1 month of tyrosine kinase inhibitor (TKI) treatment to predict therapy response. Fifty-two first-line TKI-treated CML patients were included (imatinib n = 26, dasatinib n = 21, nilotinib n = 5), and BCR-ABL1 transcript levels were measured at diagnosis (dg) and 1, 3, 6, 12, 18, 24, and 36 months. The fold change of the BCR-ABL1 transcripts at 1 month compared to initial BCR-ABL1 transcript levels was used to indicate early therapy response. In our cohort, 21% of patients had no decrease in BCR-ABL1 transcript levels after 1 month and were classified as poor responders. Surprisingly, these patients had lower BCR-ABL1 transcript levels at dg compared to responders (31% vs. 48%, p = 0.0083). Poor responders also significantly more often had enlarged spleen (55% vs. 15%; p<0.01) and a higher percentage of Ph+ CD34+CD38- cells in the bone marrow (91% vs. 75%, p<0.05). The major molecular response rates were inferior in the poor responders (at 12m 18% vs. 64%, p<0.01; 18m 27% vs. 75%, p<0.01; 24m 55% vs. 87%, p<0.01). In conclusion, early treatment response analysis defines a biologically distinct patient subgroup with inferior long-term outcomes.