Chimerism analysis within 6 months of allogeneic stem cell transplantation predicts relapse in acute myeloid leukemia

Chimerism analysis within 6 months of allogeneic stem cell transplantation predicts relapse in acute myeloid leukemia
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DOI:
10.1038/sj.bmt.1705582
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发表时间:
2007-03-01
影响因子:
4.8
通讯作者:
Verdonck, L. F.
Verdonck, L. F.
中科院分区:
医学3区
文献类型:
--
作者:
Huisman, C.;De Weger, R. A.;Verdonck, L. F.

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嵌合分析作为造血干细胞移植(SCT)后复发的预后指标的作用是有争议的。我们通过短串联重复聚合酶链反应(PCR)监测T细胞和非T细胞亚群的嵌合状态,并回顾性评估96例急性髓性白血病患者在骨髓清除(MA)或低强度调节SCT后的临床结果。MA组80例患者中有56%在所有时间点表现出完全供体嵌合(CC),而6%的混合嵌合(MC)减少,8%的稳定嵌合,25%的MC增加和3%的MC增加和减少。在16例RIC患者中,这些百分比分别为12%,50%,6%,6%和19%,以及6%的未移植。96名患者中有43人复发。复发前的最后一次嵌合评估显示,只有8例患者的MC增加。在SCT后1至6个月的样本中,与MC/ MC增加相比,CC/ MC减少与较低的复发风险(31%对83%,P < 0.000)和死亡率(38%对83%,P < 0.000)显著相关。然而,复发的发展非常迅速。只有通过高度敏感的方法对嵌合状态进行非常频繁的监测,才能识别即将发生的复发,并允许早期免疫干预。
The role of chimerism analysis as a prognostic indicator of relapse after hematopoietic stem cell transplantation (SCT) is controversial. We monitored chimerism status by short tandem repeat-based polymerase chain reaction (PCR) in T- and non-T-cell subsets and retrospectively evaluated clinical outcome in 96 patients with acute myeloid leukemia after myeloablative (MA) or reduced-intensity conditioning SCT. Fifty-six percent of 80 patients in the MA group demonstrated complete donor chimerism (CC) at all time points, whereas 6% had decreasing mixed chimerism (MC), 8% stable MC, 25% increasing MC and 3% increasing and decreasing MC. In 16 RIC patients, these percentages were 12, 50, 6, 6 and 19, respectively, together with 6% nonengraftment. Forty-three out of 96 patients experienced relapse. The last chimerism evaluation before relapse revealed increasing MC in only eight patients. In samples taken between 1 and 6 months post SCT, CC/decreasing MC was significantly related with a lower risk of relapse (31 versus 83%, P < 0.000) and mortality (38 versus 83%, P < 0.000) than with MC/ increasing MC. However, the development of relapse was very rapid. Only very frequent monitoring of chimerism status by highly sensitive methods might identify impending relapse and allow early immunological intervention.