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通过短串联重复序列嵌合体分析监测异基因骨髓移植后的残留疾病并指导供体白细胞输注。

Monitoring of residual disease and guided donor leucocyte infusion after allogeneic bone marrow transplantation by chimaerism analysis with short tandem repeats.

作者信息

de Weger R A, Tilanus M G, Scheidel K C, van den Tweel J G, Verdonck L F

机构信息

Departments of Pathology and Haematology, University Medical Centre, Utrecht, The Netherlands.

出版信息

Br J Haematol. 2000 Sep;110(3):647-53. doi: 10.1046/j.1365-2141.2000.02233.x.

DOI:10.1046/j.1365-2141.2000.02233.x
PMID:10997977
Abstract

In this study, we analysed the chimaeric status of peripheral blood leucocytes (PBLs) in recipients of allogeneic bone marrow transplantation (BMT) with the use of short tandem repeat (STR) microsatellite markers for monitoring the efficacy of BMT and donor leucocyte infusions (DLIs). A set of four STR markers was used with a highly discrimative capacity between individuals. STRs were detected by polymerase chain reaction (PCR) and were analysed by gene scanning (STR-GS). Between June 1990 and December 1998, 52 patients treated with BMT for chronic myeloid leukaemia (CML) were analysed. Seventeen patients relapsed after BMT and two patients never achieved remission after BMT. Fourteen of the 17 patients achieved a complete donor chimaerism after BMT, as detected by the presence of only donor STR-GS fragments, and in three cases a weak recipient STR-GS signal remained persistently detectable after BMT. A reappearance or increase of recipient STR-GS signals was indicative of relapse, which was mostly detected by STR-GS several months before relapse was diagnosed clinically. Nineteen patients were treated with DLI for reappearance of CML after BMT which resulted in complete remission in 17 patients, concordant with the disappearance of recipient STR-GS signals. More importantly, DLI treatment could be guided based upon the STR-GS data, which prevented unnecessary extra DLI courses that could cause toxicity. This study indicates that STR-GS is an effective and reliable method for monitoring BMT recipients.

摘要

在本研究中,我们利用短串联重复序列(STR)微卫星标记分析了异基因骨髓移植(BMT)受者外周血白细胞(PBLs)的嵌合状态,以监测BMT和供体白细胞输注(DLI)的疗效。使用一组四个具有高度个体鉴别能力的STR标记。通过聚合酶链反应(PCR)检测STR,并通过基因扫描(STR-GS)进行分析。在1990年6月至1998年12月期间,对52例接受BMT治疗慢性髓性白血病(CML)的患者进行了分析。17例患者在BMT后复发,2例患者在BMT后未达到缓解。17例患者中有14例在BMT后实现了完全供体嵌合,通过仅存在供体STR-GS片段检测到,在3例中,BMT后仍持续可检测到微弱的受者STR-GS信号。受者STR-GS信号的再次出现或增加表明复发,这大多在临床诊断复发前数月通过STR-GS检测到。19例患者在BMT后因CML复发接受了DLI治疗,其中17例患者完全缓解,这与受者STR-GS信号的消失一致。更重要的是,可以根据STR-GS数据指导DLI治疗,这避免了可能导致毒性的不必要的额外DLI疗程。本研究表明,STR-GS是监测BMT受者的一种有效且可靠的方法。

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Monitoring of residual disease and guided donor leucocyte infusion after allogeneic bone marrow transplantation by chimaerism analysis with short tandem repeats.通过短串联重复序列嵌合体分析监测异基因骨髓移植后的残留疾病并指导供体白细胞输注。
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