Failure of immunologic purging in mantle cell lymphoma assessed by polymerase chain reaction detection of minimal residual disease
Failure of immunologic purging in mantle cell lymphoma assessed by polymerase chain reaction detection of minimal residual disease
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DOI：
10.1182/blood.v90.10.4212
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发表时间：
1997-11-15
期刊：
影响因子：
20.3
通讯作者：
Gribben, JG
中科院分区：
文献类型：
--
作者：
Andersen, NS;Donovan, JW;Gribben, JG
为了评估通过聚合酶链反应（PCR）检测微小残留病（MRD）的临床意义，我们分析了在丹娜 - 法伯癌症研究所接受骨髓移植（BMT）的26例套细胞淋巴瘤（MCL）患者的样本。在研究的26例MCL患者中，有19例（73%）的BCL - 1/IgH易位以及克隆重排的Ig重链基因（IgH）为通过聚合酶链反应（PCR）扩增检测和随访MRD提供了分子标记。IgH基因测序分析显示，MCL中存在体细胞突变，这是抗原驱动过程的特征，表明在MCL中，最终的恶性转化发生在成熟B细胞中。在19例具有可通过PCR扩增标记的患者中，17例接受了自体骨髓移植，1例接受了异基因骨髓移植，1例接受了同基因骨髓移植。所有患者在骨髓移植时骨髓（BM）中都有可通过PCR检测到的MRD，无论是否有骨髓组织学受累病史。与其他B细胞恶性肿瘤不同，我们发现用补体介导的裂解进行免疫净化仅在2例患者中根除了可通过PCR检测到的MCL。此外，MRD的回输与不良预后相关。在自体骨髓移植后2年重新分期时，超过一半接受自体骨髓移植的患者已经复发。在4例未回输残留淋巴瘤的MCL患者中，包括异基因和同基因骨髓移植患者，只有1例复发。骨髓移植后MRD检测持续存在也与高复发概率相关，尽管有1例患者在淋巴结部位复发前外周血或骨髓中没有可通过PCR检测到的MRD。我们得出结论，对疾病特异性标记进行PCR扩增是一种评估MCL患者MRD及其临床意义的可行且敏感的方法。此外，PCR扩增为评估净化和干细胞采集程序的改进提供了一种工具，这些改进可能是治疗这种原本无法治愈的疾病所必需的。（C）1997年，美国血液学会
To assess the clinical significance of minimal residual disease (MRD) detection by polymerase chain reaction (PCR) we analyzed samples from 26 patients with mantle cell lymphoma (MCL) who had undergone bone marrow transplantation (BMT) at the Dana-Farber Cancer Institute. The BCL-1/lgH translocation and clonally rearranged lg heavy chain genes (lgH) provided molecular markers for detection and follow-up of MRD by polymerase chain reaction (PCR) amplification in 19 of the 26 (73%) MCL patients studied. lgH gene sequencing analysis showed somatic mutations in MCL that are characteristic of an antigen driven process suggesting that, in MCL, the final malignant transformation occurs in a mature B cell. Of the 19 patients with a PCR amplifiable marker, 17 underwent autologous, 1 an allogeneic, and 1 a syngeneic bone marrow transplantation (BMT). All patients had PCR-detectable MRD in the bone marrow (BM) at the time of BMT, irrespective of any history of histological BM involvement. In contrast to other B-cell malignancies, we found that immunological purging with complement-mediated lysis eradicated PCR-detectable MCL in only two patients. Moreover reinfusion of MRD was associated with a poor outcome. More than half of the patients undergoing autologous BMT had relapsed by the time of restaging at 2 years after autologous BMT. In four MCL patients in whom no residual lymphoma was reinfused, including the allogeneic and the syngeneic BMT, only one patient relapsed. Persistence of MRD detection after BMT was also associated with a high probability of relapse, although one patient did not have PCR-detectable MRD in peripheral blood or BM before relapse at nodal sites. We conclude that PCR amplification of disease-specific markers is a feasible and sensitive method to assess MRD and its clinical significance in patients with MCL. Moreover, PCR amplification provides a tool to evaluate modifications of purging and stem cell collection procedures that may be required for the management of this otherwise incurable disease. (C) 1997 by The American Society of Hematology.