Cole-Sinclair M F, Foroni L, Hoffbrand A V
Department of Haematology, Royal Free Hospital Medical School, Hampstead, London, UK.
Baillieres Clin Haematol. 1994 Jun;7(2):183-233. doi: 10.1016/s0950-3536(05)80200-8.
Cure can now be achieved in a proportion of patients with ALL. However, relapse and eventual treatment failure occur in many cases receiving identical treatment, presumably as a result of failure to eradicate MRD. While for many years marrow morphology has been the standard by which leukaemic remission has been assessed, more sensitive techniques have been developed for detection of MRD including immunophenotypic analysis, and as discussed in this chapter, methods which detect leukemia-associated clonal genetic changes at the karyotypic and genomic levels. Table 10 lists the applicability and sensitivity of various markers used in MRD analysis in ALL. It is apparent that of the karyotypic and molecular approaches described, only PCR-based strategies for detection of either leukaemia-specific translocations or clonal Ag receptor rearrangements are reliably applicable to a high proportion of both B- and T-ALL at sufficiently high sensitivity. Initial clinical studies of patients undergoing therapy for ALL using a variety of PCR-based methods suggest that in some cases a persistent or increasing level of residual disease may be predictive for clinical relapse, although a number of technical factors and the phenomena of oligo-clonality and clonal evolution may limit the usefulness of this analysis in a few instances. From current available data it appears that in order to define the potential predictive value of PCR detection of MRD a large number of patients will need to be prospectively assessed over several years at multiple time points during and after therapy, preferably using more than one semi-quantitative PCR approach. In addition to reliable prediction of clinical relapse allowing appropriate individual treatment modification, progress in the molecular detection of MRD in ALL is also likely to be of benefit in the assessment of the efficacy of autograft purging and the evaluation of new therapeutic strategies such as the use of biological response modifiers to eliminate a low tumour burden.
现在，一部分急性淋巴细胞白血病（ALL）患者能够被治愈。然而，许多接受相同治疗的患者会出现复发并最终治疗失败，推测这是由于未能根除微小残留病（MRD）所致。多年来，骨髓形态学一直是评估白血病缓解情况的标准，但已开发出更敏感的技术来检测MRD，包括免疫表型分析，并且如本章所讨论的，还有在核型和基因组水平检测白血病相关克隆基因变化的方法。表10列出了ALL中MRD分析所使用的各种标志物的适用性和敏感性。很明显，在所描述的核型和分子方法中，只有基于聚合酶链反应（PCR）的策略，用于检测白血病特异性易位或克隆性抗原受体重排，能够以足够高的敏感性可靠地应用于高比例的B-ALL和T-ALL。使用多种基于PCR的方法对接受ALL治疗的患者进行的初步临床研究表明，在某些情况下，残留疾病水平持续或升高可能预示临床复发，尽管一些技术因素以及寡克隆性和克隆进化现象可能在少数情况下限制这种分析的实用性。从目前可得的数据来看，为了确定PCR检测MRD的潜在预测价值，需要在数年时间里对大量患者在治疗期间和治疗后的多个时间点进行前瞻性评估，最好使用不止一种半定量PCR方法。除了能够可靠地预测临床复发从而允许进行适当的个体化治疗调整外，ALL中MRD分子检测的进展还可能有助于评估自体移植净化的疗效以及评估新的治疗策略，如使用生物反应调节剂来消除低肿瘤负荷。
