Seiden M V, Anderson K C
Division of Hematology and Oncology, Massachusetts General Hospital, Boston, USA.
J Infus Chemother. 1996 Winter;6(1):17-22.
Over the last several years there has been significant progress in developing several techniques designed to detect contaminating tumor cells in bone marrow (BM) and peripheral blood progenitor cells (PBPC). These techniques include immunohistochemistry, in situ hybridization (ISH), flow cytometry, clonogenic tumor assays, and polymerase chain reaction (PCR) based assays. These assays have detection capabilities ranging from 1 tumor cell in 100 normal cells (ISH) to 1 tumor cell in a million tumor cells (RT-PCR). These techniques have confirmed that BM and PBPC are frequently contaminated with tumor cells, with most studies suggesting higher tumor contamination in the BM as compared to the PBPC. Comparison of immunocytochemistry with the clonogenic assay has demonstrated good but not perfect correlation of these two techniques. Gene marking studies have confirmed that these tumor cells are viable and capable of contributing to disease relapse. Many of the assays are at least semiquantitative and are effective at monitoring for persistent residual tumor cell contamination after ex vivo processing of autografts including purging strategies and/or positive selection techniques. Preliminary data are conflicting, although some data suggest that patients receiving autografts with residual tumor cell contamination do worse than patients receiving autografts free of detectable tumor cells. Many purging techniques are capable of reducing tumor contamination by 3 to 5 logs; positive selection techniques are probably slightly less effective, reducing tumor contamination by 3 to 4 logs. The clinical benefit of purging remains to be demonstrated in randomized clinical trials.
在过去几年中，在开发多种旨在检测骨髓（BM）和外周血祖细胞（PBPC）中污染性肿瘤细胞的技术方面取得了显著进展。这些技术包括免疫组织化学、原位杂交（ISH）、流式细胞术、克隆形成肿瘤检测以及基于聚合酶链反应（PCR）的检测。这些检测方法的检测能力范围从每100个正常细胞中检测出1个肿瘤细胞（ISH）到每百万个肿瘤细胞中检测出1个肿瘤细胞（逆转录PCR）。这些技术已经证实，BM和PBPC经常被肿瘤细胞污染，大多数研究表明，与PBPC相比，BM中的肿瘤污染更高。免疫细胞化学与克隆形成检测的比较表明，这两种技术之间存在良好但并非完美的相关性。基因标记研究证实，这些肿瘤细胞是有活力的，并且能够导致疾病复发。许多检测方法至少是半定量的，并且在监测自体移植物体外处理（包括清除策略和/或阳性选择技术）后持续存在的残留肿瘤细胞污染方面是有效的。初步数据相互矛盾，尽管一些数据表明，接受有残留肿瘤细胞污染的自体移植物的患者比接受无可检测肿瘤细胞的自体移植物的患者情况更差。许多清除技术能够将肿瘤污染降低3至5个对数；阳性选择技术可能效果稍差，将肿瘤污染降低3至4个对数。清除的临床益处仍有待在随机临床试验中得到证实。
