Miflin G, Stainer C J, Carter G I, Byrne J L, Haynes A P, Russell N H
Department of Haematology, Nottingham City Hospital.
Br J Haematol. 1999 Nov;107(2):429-40. doi: 10.1046/j.1365-2141.1999.01709.x.
Serial samples were collected from 38 patients following allogeneic transplantation using either unmanipulated peripheral blood stem cells (PBSC) (n = 18) or bone marrow (BM) (n = 20) to assess the incidence of mixed chimaerism using PCR amplification of five VNTR regions. After amplification, products were analysed using the Applied Biosystems ABI PRISM 377 Automated DNA Sequencer and GeneScan software GenoTyper program to determine a quantitative measure of chimaerism. The sensitivity of detection using this method was 0.1%. In the immediate post-transplant period (up to day 30) a significantly lower incidence of mixed chimaerism (MC) occurred in recipients of PBSC compared to BM (P < 0.0005). Between 1 and 6 months there was a significantly lower incidence of low-level MC in patients receiving PBSCT compared to BMT (4/14 v 8/11 respectively, P = 0.04) in patients who had not rejected their grafts or relapsed. Similarly, beyond 6 months 0/9 PBSCT patients compared to 4/9 BMT patients showed MC (P = 0.02). Beyond day 30 13/33 (39%) patients showed intermittent low-level MC, but this was not predictive for subsequent relapse. A rapidly increasing proportion of recipient haemopoiesis was predictive of graft rejection or relapse. Stable continuous MC without relapse was seen in one patient transplanted with PBSC for severe aplastic anaemia. These results suggest that the incidence of intermittent low-level MC is relatively high in the first 6 months following unmanipulated haemopoietic stem cell transplantation but reduces with time and is significantly lower in recipients of PBSC.
对38例接受异基因移植的患者采集系列样本,这些患者使用的是未处理的外周血干细胞(PBSC)(n = 18)或骨髓(BM)(n = 20),通过对五个VNTR区域进行PCR扩增来评估混合嵌合体的发生率。扩增后,使用应用生物系统公司的ABI PRISM 377自动DNA测序仪和GeneScan软件的GenoTyper程序分析产物,以确定嵌合体的定量指标。使用该方法的检测灵敏度为0.1%。在移植后的即刻阶段(至第30天),接受PBSC的患者中混合嵌合体(MC)的发生率显著低于接受BM的患者(P < 0.0005)。在1至6个月期间,未发生移植物排斥或复发的患者中,接受PBSCT的患者低水平MC的发生率显著低于接受BMT的患者(分别为4/14和8/11,P = 0.04)。同样,在6个月之后,0/9例接受PBSCT的患者与4/9例接受BMT的患者出现MC(P = 0.02)。在第30天之后,13/33(39%)的患者出现间歇性低水平MC,但这对随后的复发并无预测价值。受者造血迅速增加的比例可预测移植物排斥或复发。1例因严重再生障碍性贫血接受PBSC移植的患者出现了稳定持续的MC且未复发。这些结果表明,在未处理的造血干细胞移植后的前6个月,间歇性低水平MC的发生率相对较高,但随时间降低,且在接受PBSC的患者中显著更低。