ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death.
ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death.
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DOI：
10.1056/nejmoa1213299
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发表时间：
2013-08-08
期刊：
影响因子：
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通讯作者：
Paczesny S
中科院分区：
文献类型：
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作者：
Vander Lugt MT;Braun TM;Hanash S;Ritz J;Ho VT;Antin JH;Zhang Q;Wong CH;Wang H;Chin A;Gomez A;Harris AC;Levine JE;Choi SW;Couriel D;Reddy P;Ferrara JL;Paczesny S
没有血浆生物标志物与异基因造血干细胞移植后急性移植物抗宿主病（GVHD）治疗的反应相关。我们比较了 10 名在治疗开始后第 28 天完全缓解的患者在治疗开始后中位 16 天时获得的血浆中的 12 种生物标志物，以及从治疗期间患有进展性 GVHD 的 10 名患者获得的血浆中的 12 种生物标志物。在治疗开始时对 381 名患者的血浆中的主要生物标志物致瘤性抑制 2 (ST2) 进行了测量，并在移植后的第一个月内对三组独立的总共 673 名患者进行了测量，以确定该生物标志物与难治性 GVHD 以及治疗或移植后 6 个月死亡率的关联。在 12 种标志物中，ST2 与 GVHD 治疗耐药和随后无复发的死亡具有最显着的相关性。与治疗开始时 ST2 值较低的患者相比，ST2 值较高的患者出现难治性 GVHD 的可能性是其 2.3 倍（95% 置信区间 [CI]，1.5 至 3.6），治疗后 6 个月内死亡的可能性是其 3.7 倍（95% CI，2.3 至 5.9）。无论 GVHD 级别如何，低 ST2 值患者的无复发死亡率均低于高 ST2 值患者（I 级或 II 级 GVHD 患者为 11% vs. 31%，III 级或 IV 级 GVHD 患者为 14% vs. 67%，两种比较 P<0.001）。无论预处理方案的强度如何，移植后第 14 天的血浆 ST2 值与无复发的 6 个月死亡率相关。在 GVHD 治疗开始时和移植后第一个月内测量的 ST2 水平改善了难治性 GVHD 和移植后无复发死亡的风险分层。 （由美国国立卫生研究院资助。）
No plasma biomarkers are associated with the response of acute graft-versus-host disease (GVHD) to therapy after allogeneic hematopoietic stem-cell transplantation. We compared 12 biomarkers in plasma obtained a median of 16 days after therapy initiation from 10 patients with a complete response by day 28 after therapy initiation and in plasma obtained from 10 patients with progressive GVHD during therapy. The lead biomarker, suppression of tumorigenicity 2 (ST2), was measured at the beginning of treatment for GVHD in plasma from 381 patients and during the first month after transplantation in three independent sets totaling 673 patients to determine the association of this biomarker with treatment-resistant GVHD and 6-month mortality after treatment or transplantation. Of the 12 markers, ST2 had the most significant association with resistance to GVHD therapy and subsequent death without relapse. As compared with patients with low ST2 values at therapy initiation, patients with high ST2 values were 2.3 times as likely to have treatment-resistant GVHD (95% confidence interval [CI], 1.5 to 3.6) and 3.7 times as likely to die within 6 months after therapy (95% CI, 2.3 to 5.9). Patients with low ST2 values had lower mortality without relapse than patients with high ST2 values, regardless of the GVHD grade (11% vs. 31% among patients with grade I or II GVHD and 14% vs. 67% among patients with grade III or IV GVHD, P<0.001 for both comparisons). Plasma ST2 values at day 14 after transplantation were associated with 6-month mortality without relapse, regardless of the intensity of the conditioning regimen. ST2 levels measured at the initiation of therapy for GVHD and during the first month after transplantation improved risk stratification for treatment-resistant GVHD and death without relapse after transplantation. (Funded by the National Institutes of Health.)