TNF-inhibition with etanercept for graft-versus-host disease prevention in high-risk HCT: lower TNFR1 levels correlate with better outcomes.
TNF-inhibition with etanercept for graft-versus-host disease prevention in high-risk HCT: lower TNFR1 levels correlate with better outcomes.
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DOI：
10.1016/j.bbmt.2012.03.013
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发表时间：
2012-10
影响因子：
4.3
通讯作者：
Levine, John E.
中科院分区：
文献类型：
--
作者：
Choi, Sung W.;Stiff, Patrick;Cooke, Kenneth;Ferrara, James L. M.;Braun, Thomas;Kitko, Carrie;Reddy, Pavan;Yanik, Gregory;Mineishi, Shin;Paczesny, Sophie;Hanauer, David;Pawarode, Attaphol;Peres, Edward;Rodriguez, Tulio;Smith, Scott;Levine, John E.
移植物抗宿主病（GVHD）是替代供者（无关和错配相关）造血细胞移植（HCT）后最常见的非复发性死亡（NRM）。我们先前表明，清髓性HCT后第+7天TNF-受体-1（TNFR 1）比值（移植后第+7天/移植前基线）的增加与包括GVHD、NRM和生存率在内的结局相关。因此，我们在两个中心进行了一项II期试验，测试在标准GVHD预防中加入TNF抑制剂依那西普（25 mg，每周两次，从开始预处理到第56天）是否会降低TNFR 1水平，降低GVHD发生率，并改善NRM和生存率。使用基于全身照射（TBI）的预处理（N= 29）或基于非TBI的预处理（N = 71），患者接受了来自匹配的无关供体（N=71）、单抗原不匹配的无关供体（N = 26）或单抗原不匹配的相关供体（N=3）的清髓性HCT。与历史对照组相比，接受基于TBI的预处理的患者中移植后第+7天TNFR 1比率的增加没有改变，但接受非基于TBI的预处理的患者中降低了40%。后一组经历了相对较低的3-4级严重GVHD（14%），一年NRM（16%）和高一年生存率（69%）。这些发现表明：（1）依那西普抑制TNF的有效性可能取决于预处理方案，（2）减弱移植后早期TNFR 1水平的预期升高与良好结局相关。
Graft-versus-host disease (GVHD) causes most non-relapse mortality (NRM) following alternative donor (unrelated and mismatched related) hematopoietic cell transplant (HCT). We previously showed that increases in day +7 TNF-receptor-1 (TNFR1) ratios (post-transplant day +7/pre-transplant baseline) after myeloablative HCT correlate with outcomes including GVHD, NRM and survival. Therefore, we conducted a phase II trial at two centers testing whether the addition of the TNF-inhibitor etanercept (25 mg twice weekly from start of conditioning to day +56) to standard GVHD prophylaxis would lower TNFR1 levels, reduce GVHD rates, and improve NRM and survival. Patients underwent myeloablative HCT from a matched unrelated donor (N=71), one-antigen mismatched unrelated donor (N=26) or one-antigen mismatched related donor (N=3) using either total body irradiation (TBI)-based conditioning (N=29) or non-TBI-based conditioning (N=71). Compared to historical controls, the increase in post-transplant day +7 TNFR1 ratios was not altered in patients who received TBI-based conditioning, but was 40% lower in patients receiving non-TBI-based conditioning. The latter group experienced relatively low rates of severe grade 3-4 GVHD (14%), one-year NRM (16%), and high one-year survival (69%). These findings suggest that (1) the effectiveness of TNF-inhibition with etanercept may depend on the conditioning regimen, and (2) attenuating the expected rise in TNFR1 levels early post-transplant correlates with good outcomes.
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影响因子：
4.8
作者：
Uberti JP;Agovi MA;Tarima S;Haagenson M;Gandham S;Anasetti C;Baker KS;Bolwell BJ;Bornhauser M;Chan KW;Copelan E;Davies SM;Finke J;Hale GA;Kollman C;McCarthy PL;Ratanatharathorn V;Ringdén O;Weisdorf DJ;Rizzo JD
通讯作者：
Rizzo JD
影响因子：
11.8
作者：
Ascioglu, S;Rex, JH;Walsh, TJ
通讯作者：
Walsh, TJ
影响因子：
3.1
作者：
Giles, Jon T;Bathon, Joan M
通讯作者：
Bathon, Joan M
使用来自匹配的非相关供体的同种异体造血干细胞移植治疗的骨髓恶性肿瘤患者的结果与使用 10 个位点的 HLA 分型的一种人类白细胞抗原不匹配的相关供体进行比较。
影响因子：
4.3
作者：
Ciurea, Stefan O.;Saliba, Rima M.;Rondon, Gabriela;Patah, Paliana A.;Aung, Fleur;Cano, Pedro;Andersson, Borje S.;Kebriaei, Partow;Papat, Uday;Fernandez-Vina, Marcelo;Champlin, Richard E.;de Lima, Marcos
通讯作者：
de Lima, Marcos
影响因子：
10.1
作者：
Juvonen, Eeva;Aalto, Sanna;Ruutu, Tapani
通讯作者：
Ruutu, Tapani