Sarasquete María Eugenia, García-Sanz Ramón, González David, Martínez Joaquín, Mateo Gema, Martínez Pilar, Ribera José Maria, Hernández José Mariano, Lahuerta Juan José, Orfão Alberto, González Marcos, San Miguel Jesus F
Grupo Español de Mieloma (GEM-PETHEMA), Red Española de Mieloma (G03/136), Servicio de Hematología, Hospital Universitario de Salamanca, Centro de Investigación del Cáncer (CIC), Universidad de Salamanca, Spain.
Haematologica. 2005 Oct;90(10):1365-72.
Minimal residual disease (MRD) studies are useful in multiple myeloma (MM). However, the definition of the best technique and clinical utility are still unresolved issues. The aim of this study was to analyze and compare the clinical utility of MRD studies in MM with two different techniques: allelic-specific oligonucleotide real-time quantitative PCR (ASO-RQ-PCR), and flow cytometry (FCM).
Bone marrow samples from 32 MM patients who had achieved complete response after transplantation were evaluated by ASO-RQ-PCR, using TaqMan technology, and multiparametric FCM.
ASO-RQ-PCR was only applicable in 75% of patients for a variety of technical reasons, while FCM was applicable in up to 90%. Therefore, simultaneous PCR/FCM analysis was possible in only 24 patients. The number of residual tumor cells identified by both techniques was very similar (mean=0.29%, range=0.001-1.61%, correlation coefficient=0.861). However, RQ-PCR was able to detect residual myelomatous cells in 17 patients while FCM only did so in 11; thus, 6 cases were FCM negative but PCR positive, all of them displaying a very low number of clonal cells (median=0.014%, range=0.001-0.11). Using an MRD threshold of 0.01% (10(-4)) two risk groups with significantly different progression-free survival could be identified by either PCR (34 vs. 15m, p=0.04) or FCM (27 vs. 10m, p=0.05).
Although MRD evaluation by ASO-RQ-PCR is slightly more sensitive and specific than FCM, it is applicable in a lower proportion of MM patients and is more time-consuming, while both techniques provide similar prognostic information.
微小残留病（MRD）研究在多发性骨髓瘤（MM）中具有重要意义。然而，最佳检测技术的定义及其临床应用仍未解决。本研究旨在分析和比较两种不同技术——等位基因特异性寡核苷酸实时定量聚合酶链反应（ASO-RQ-PCR）和流式细胞术（FCM）——在MM中进行MRD研究的临床应用价值。
对32例移植后达到完全缓解的MM患者的骨髓样本，采用TaqMan技术通过ASO-RQ-PCR以及多参数FCM进行评估。
由于各种技术原因，ASO-RQ-PCR仅适用于75%的患者，而FCM的适用率高达90%。因此，仅24例患者能够同时进行PCR/FCM分析。两种技术鉴定出的残留肿瘤细胞数量非常相似（平均值=0.29%，范围=0.001 - 1.61%，相关系数=0.861）。然而，RQ-PCR能够检测出17例患者中的残留骨髓瘤细胞，而FCM仅检测出11例；因此，有6例患者FCM检测为阴性但PCR检测为阳性，所有这些病例中克隆细胞数量都非常少（中位数=0.014%，范围=0.001 - 0.11）。使用0.01%（10⁻⁴）的MRD阈值，通过PCR（34个月对15个月，p = 0.04）或FCM（27个月对10个月，p = 0.05）均可识别出无进展生存期显著不同的两个风险组。
尽管通过ASO-RQ-PCR评估MRD比FCM稍敏感且特异，但它在MM患者中的适用比例较低且耗时较长，而两种技术提供的预后信息相似。
