Sensitivity of hematological malignancies to graft-versus-host effects: an EBMT megafile analysis
Sensitivity of hematological malignancies to graft-versus-host effects: an EBMT megafile analysis
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DOI：
10.1038/leu.2014.145
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发表时间：
2014-11-01
期刊：
影响因子：
11.4
通讯作者：
Ruutu, T.
中科院分区：
文献类型：
--
作者：
Stern, M.;de Wreede, L. C.;Ruutu, T.
异基因干细胞移植后，通过供体T淋巴细胞识别组织相容性错配而发生移植物抗宿主病（GvHD）。同样的机制也可以消除恶性细胞（移植物抗肿瘤效应或GvT效应）。我们假设，比较GvHD和复发之间的相关性可能会提供一个替代标志物的疾病的易感性同种免疫效应。我们研究了1998年至2007年间进行的48111例首次同种异体移植。在慢性粒细胞白血病（CML）中，复发风险明显下降，并与急性和慢性GvHD的严重程度成比例。急性淋巴细胞白血病和BCR-ABL阴性骨髓增生性肿瘤对GvHD的敏感性低于CML，而骨髓增生异常综合征和淋巴增生性疾病的敏感性居中。GvHD仅与急性髓性白血病（AML）和浆细胞疾病（PCD）复发风险的适度降低相关。除PCD外，所有疾病的复发风险率在随访48个月时几乎降至0。这些数据证实了与GvHD相关的有效GvT效应的观察结果。GvHD/GvT相关性的强度在血液系统恶性肿瘤之间显著不同。尽管GvHD/GvT比值存在差异，但不同疾病的复发率平行下降，表明GvT效应可能在没有GvHD的情况下起作用，特别是在AML中。
After allogeneic stem cell transplantation, graft-versus-host disease (GvHD) occurs through recognition of histocompatibility mismatches by donor T lymphocytes. The same mechanism operates in eliminating malignant cells (the graft-versus-tumor or GvT effect). We hypothesized that comparing the correlation between GvHD and relapse might provide a surrogate marker for the susceptibility of diseases to allo-immune effects. We studied 48 111 first allogeneic transplants performed between 1998 and 2007. In chronic myeloid leukemia (CML), the relapse risk declined clearly and proportionally to severity of acute and chronic GvHD. Acute lymphoblastic leukemia and BCR-ABL-negative myeloproliferative neoplasias were comparably sensitive to GvHD as CML, whereas myelodysplastic syndromes and lymphoproliferative disorders showed intermediate sensitivity. GvHD was only associated with modest reductions in relapse risk in acute myeloid leukemia (AML) and plasma cell disorders (PCDs). Except for PCD, hazard rates for relapse decreased to almost 0 at 48 months of follow-up in all diseases. These data confirm observations of potent GvT effects associated with GvHD. The strength of the GvHD/GvT correlation differs significantly between hematological malignancies. The parallel drop of relapse rates in different diseases despite differences in GvHD/GvT ratios suggests that GvT effects might operate in the absence of GvHD, particularly in AML.