Abteilung Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Am Klinikum 1, 07740, Jena, Germany.
Abteilung für Hämatologie und internistische Onkologie, Universität Leipzig, Leipzig, Germany.
J Cancer Res Clin Oncol. 2019 Jun;145(6):1645-1650. doi: 10.1007/s00432-019-02910-6. Epub 2019 Apr 2.
The advent of tyrosine kinase inhibitor (TKI) therapies has revolutionized the treatment of chronic myeloid leukemia (CML). The European LeukemiaNet (ELN) recommends quantification of BCR-ABL1 transcripts by real-time quantitative PCR every 3 months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR, MR, MR) maintain remission after treatment stop, assessment of DMR is crucial. However, systematically collected molecular data, monitored with sensitive standardized assays, are not available outside clinical trials.
Data were collected on the standardized assessment of molecular response in the context of real-life practice. BCR-ABL1 transcript levels after > 2 years of TKI therapy were evaluated for DMR by local laboratories as well as standardized EUTOS laboratories. Since standardized molecular monitoring is a prerequisite for treatment discontinuation, central surveillance of the performance of the participating laboratories was carried out.
Between 2014 and 2017, 3377 peripheral blood samples from 1117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCR-ABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of the patients, the initial transcript type had not been reported. Response levels (EUTOS laboratory) were: no MMR, n = 197 (6.51%); MMR, n = 496 (16.40%); MR, n = 685 (22.64%); MR, n = 937 (30.98%); MR, n = 710 (23.47%). With a Cohen's kappa coefficient of 0.708, a substantial agreement between EUTOS-certified and local laboratories was shown.
Multicenter DMR assessment is feasible in the context of real-life clinical practice in Europe. Information on the BCR-ABL1 transcript type at diagnosis is crucial to accurately monitor patients' molecular response during or after TKI therapy.
酪氨酸激酶抑制剂（TKI）治疗的出现彻底改变了慢性髓性白血病（CML）的治疗方式。欧洲白血病网络（ELN）建议在 TKI 治疗期间每 3 个月通过实时定量 PCR 定量检测 BCR-ABL1 转录本。由于一部分在深度分子反应（DMR：MR 、MR 、MR ）中达到缓解的患者在治疗停止后仍能维持缓解，因此评估 DMR 至关重要。然而，在临床试验之外，并没有系统收集的分子数据，也没有使用敏感的标准化检测方法进行监测。
本研究收集了在真实环境下对分子缓解进行标准化评估的数据。当地实验室以及标准化 EUTOS 实验室评估了 TKI 治疗>2 年后的 DMR 患者的 BCR-ABL1 转录本水平。由于标准化分子监测是停止治疗的前提，因此对参与实验室的性能进行了集中监测。
2014 年至 2017 年，3377 份来自 1117 例 CML 患者的外周血样本被送到六个欧洲国家的 11 个标准化参考实验室。BCR-ABL1 转录本类型为 b3a2（41.63%）、b2a2（29.99%）、b2a2/b3a2（3.58%）和非典型（0.54%）。对于 23.72%的患者，初始转录本类型未报告。EUTOS 实验室的反应水平为：无主要分子学缓解（MMR），n=197（6.51%）；MMR，n=496（16.40%）；MR ，n=685（22.64%）；MR ，n=937（30.98%）；MR ，n=710（23.47%）。Cohen's kappa 系数为 0.708，EUTOS 认证实验室与当地实验室之间具有高度一致性。
在欧洲的真实临床实践中，多中心 DMR 评估是可行的。在 TKI 治疗期间或之后，诊断时有关 BCR-ABL1 转录本类型的信息对于准确监测患者的分子反应至关重要。
