Department of Medical and Surgical Sciences, Section of Hematology, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Via del Pozzo 71, 41124 Modena, Italy.
Pediatric Hematology/Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy.
Int J Mol Sci. 2018 Nov 6;19(11):3492. doi: 10.3390/ijms19113492.
Acute myeloid leukemia (AML) with gene mutations is currently recognized as a distinct entity, due to its unique biological and clinical features. We summarize here the results of published studies investigating the clinical application of minimal/measurable residual disease (MRD) in patients with -mutated AML, receiving either intensive chemotherapy or hematopoietic stem cell transplantation. Several clinical trials have so far demonstrated a significant independent prognostic impact of molecular MRD monitoring in -mutated AML and, accordingly, the Consensus Document from the European Leukemia Net MRD Working Party has recently recommended that -mutated AML patients have MRD assessment at informative clinical timepoints during treatment and follow-up. However, several controversies remain, mainly with regard to the most clinically significant timepoints and the MRD thresholds to be considered, but also with respect to the optimal source to be analyzed, namely bone marrow or peripheral blood samples, and the correlation of MRD with other known prognostic indicators. Moreover, we discuss potential advantages, as well as drawbacks, of newer molecular technologies such as digital droplet PCR and next-generation sequencing in comparison to conventional RQ-PCR to quantify -mutated MRD. In conclusion, further prospective clinical trials are warranted to standardize MRD monitoring strategies and to optimize MRD-guided therapeutic interventions in -mutated AML patients.
急性髓系白血病（AML）伴基因突变目前被认为是一种独特的实体，因其具有独特的生物学和临床特征。我们在这里总结了关于接受强化化疗或造血干细胞移植的突变 AML 患者中微小残留病（MRD）临床应用的已发表研究结果。到目前为止，几项临床试验已经证明了分子 MRD 监测在突变 AML 中的显著独立预后影响，因此，欧洲白血病网 MRD 工作组的共识文件最近建议突变 AML 患者在治疗和随访期间的有意义的临床时间点进行 MRD 评估。然而，仍存在一些争议，主要涉及最具临床意义的时间点和要考虑的 MRD 阈值，但也涉及要分析的最佳来源，即骨髓或外周血样本，以及 MRD 与其他已知预后指标的相关性。此外，我们还讨论了与传统实时定量 PCR（RQ-PCR）相比，新型分子技术（如数字液滴 PCR 和下一代测序）在定量突变 MRD 方面的潜在优势和缺点。总之，需要进一步的前瞻性临床试验来标准化 MRD 监测策略，并优化突变 AML 患者的 MRD 指导治疗干预。
