Zanaglio Camilla, Bernardi Simona, Gandolfi Lisa, Farina Mirko, Re Federica, Polverelli Nicola, Zollner Tatiana, Turra Alessandro, Morello Enrico, Malagola Michele, Russo Domenico
Chair of Hematology, Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy.
CREA Laboratory (Centro di Ricerca Emato-Oncologica AIL), ASST Spedali Civili di Brescia, Brescia, Italy.
Case Rep Oncol. 2020 Oct 15;13(3):1263-1269. doi: 10.1159/000510440. eCollection 2020 Sep-Dec.
Real-time quantitative PCR (RT-qPCR) is the gold standard to quantify the BCR-ABL1 transcript for molecular response monitoring in chronic myeloid leukemia (CML) patients, and it plays a pivotal role in clinical decision-making process, even if it presents technical limits. Increasing data suggest that digital PCR (dPCR) is more accurate and reliable than RT-qPCR in CML minimal residual disease monitoring and in patients' selection for treatment discontinuation. But what about the identification of treatment discontinuation failures? We present the case of a CML patient enrolled both in a study aiming to comparatively assess molecular response by RT-qPCR and dPCR and in the progressive arm of the OPTkIMA trial. This is a phase III trial including CML patients randomized to receive a fixed versus a progressive intermittent tyrosine kinase inhibitor regimen. At 24 months, because of two consecutive detections of MR by RT-qPCR, the patient resumed daily treatment. Conversely, dPCR revealed a stability of molecular response and even a slight decreasing of transcript over time. An additional specimen was sampled one month after the first MR detection because of clinical decision: RT-qPCR resulted MR and dPCR confirmed the transcript's stability. Nowadays, the resumption of therapy is RT-qPCR-driven despite its limits in detection and robustness. In this case, according to dPCR, the patient could have continued intermittent treatment and the stability of response was then confirmed by RT-qPCR. So, dPCR could be able to better identify peculiar clinical response to therapy.
实时定量聚合酶链反应（RT-qPCR）是慢性髓性白血病（CML）患者分子反应监测中定量BCR-ABL1转录本的金标准，它在临床决策过程中起着关键作用，即使它存在技术局限性。越来越多的数据表明，在CML微小残留病监测以及选择停止治疗的患者方面，数字PCR（dPCR）比RT-qPCR更准确、可靠。但是在识别治疗中断失败方面呢？我们介绍了一例CML患者，该患者既参与了一项旨在通过RT-qPCR和dPCR比较评估分子反应的研究，也参与了OPTkIMA试验的进展组。这是一项III期试验，纳入了随机接受固定或进展性间歇酪氨酸激酶抑制剂方案的CML患者。在24个月时，由于RT-qPCR连续两次检测到微小残留病，该患者恢复了每日治疗。相反，dPCR显示分子反应稳定，甚至转录本随时间略有下降。由于临床决策，在首次检测到微小残留病一个月后采集了额外的样本：RT-qPCR结果显示为微小残留病，dPCR证实了转录本的稳定性。如今，尽管RT-qPCR在检测和稳健性方面存在局限性，但治疗的恢复仍由RT-qPCR驱动。在这种情况下，根据dPCR，患者本可以继续间歇治疗，随后RT-qPCR证实了反应的稳定性。因此，dPCR可能能够更好地识别对治疗的特殊临床反应。
