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使用短串联重复序列标记的多重PCR扩增对淋巴细胞和髓细胞混合嵌合体进行连续定量,分别预测外周血CD34+选择细胞异体移植后的移植物排斥和复发。

Serial quantification of lymphoid and myeloid mixed chimerism using multiplex PCR amplification of short tandem repeat-markers predicts graft rejection and relapse, respectively, after allogeneic transplantation of CD34+ selected cells from peripheral blood.

作者信息

Fernández-Avilés F, Urbano-Ispizua A, Aymerich M, Colomer D, Rovira M, Martínez C, Nadal E, Talarn C, Carreras E, Montserrat E

机构信息

Institute of Haematology and Oncology, Hospital Clínic of Barcelona, University of Bacelona, Spain.

出版信息

Leukemia. 2003 Mar;17(3):613-20. doi: 10.1038/sj.leu.2402854.

DOI:10.1038/sj.leu.2402854
PMID:12646952
Abstract

We used multiplex amplification of nine microsatellite sequences (PCR-STR) to analyse chimerism in pure populations of T cells and neutrophils from peripheral blood from 40 patients submitted to an allogeneic transplant, 22 having received a T-cell depleted (TCD) peripheral blood graft by means of CD34(+) selection (allo-PBT/CD34(+)), and 18, an unmodified graft (allo-SCT; 13 allogeneic bone marrow transplants and five allo-PBT). T-cell mixed chimerism (TcMC) was observed in 16 of the 22 (72.3%) patients receiving an allo-PBT/CD34(+), but in only one of the 18 (5.5%) patients receiving an allo-SCT (P=0.0001). TcMC was transient (n=6), stable (n=7), and associated with poor haematopoietic engraftment (n=4). All patients with TcMC who developed graft failure had more than 30% of host T cells. Myeloid MC (MyMC) was observed in four (19%) allo-PBT/CD34(+) patients and in three (17%) allo-SCT patients (P=NS). Five out of seven (71%) patients with MyMC relapsed, all of them diagnosed with myeloid malignancies, as compared with two of the 20 (10%) patients with complete donor chimerism (P&<0.0001). In conclusion, TcMC appears in a significant number of allo-PBT/CD34(+) patients and may be associated with poor engraftment when the percentage of host T cells is >30%; likewise, MyMC appears in a small percentage of recipients of both allo-PBT/CD34(+) and allo-SCT patients, and is associated with leukaemia relapse in myeloid malignancies.

摘要

我们采用9个微卫星序列的多重扩增(PCR-STR)技术,分析了40例接受同种异体移植患者外周血中T细胞和中性粒细胞纯群体的嵌合现象。其中22例患者通过CD34(+)选择接受了T细胞去除(TCD)的外周血移植(allo-PBT/CD34(+)),18例接受了未处理的移植(allo-SCT;13例同种异体骨髓移植和5例allo-PBT)。在接受allo-PBT/CD34(+)的22例患者中,有16例(72.3%)观察到T细胞混合嵌合(TcMC),但在接受allo-SCT的18例患者中仅1例(5.5%)观察到(P=0.0001)。TcMC为短暂性(n=6)、稳定性(n=7),且与造血植入不良相关(n=4)。所有发生移植失败的TcMC患者宿主T细胞均超过30%。在4例(19%)allo-PBT/CD34(+)患者和3例(17%)allo-SCT患者中观察到髓系嵌合(MyMC)(P=无显著性差异)。7例MyMC患者中有5例(71%)复发,均被诊断为髓系恶性肿瘤,而20例完全供体嵌合患者中有2例(10%)复发(P<0.0001)。总之,大量allo-PBT/CD34(+)患者出现TcMC,当宿主T细胞百分比>30%时可能与植入不良相关;同样,MyMC在allo-PBT/CD34(+)和allo-SCT患者的一小部分受者中出现,且与髓系恶性肿瘤的白血病复发相关。

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