Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post-allogeneic HCT
Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post-allogeneic HCT
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DOI：
10.1182/blood-2016-08-735324
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发表时间：
2017-01-12
期刊：
影响因子：
20.3
通讯作者：
Choi, Sung Won
中科院分区：
文献类型：
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作者：
Abu Zaid, Mohammad;Wu, Juan;Choi, Sung Won
最近，一项比较他克莫司/西罗莫司（Tac/Sir）与他克莫司/甲氨蝶呤（Tac/Mtx）作为匹配相关异基因造血细胞移植（HCT）后移植物抗宿主病（GVHD）预防的III期临床试验（BMT CTN 0402）显示，研究组间急性无GVHD生存期无差异。在这一前瞻性、多中心研究的背景下，采用统一的GVHD预防、预处理方案和供体来源，我们探讨了10种先前确定的生物标志物与同种异体HCT后临床结局的相关性。我们使用酶联免疫吸附试验（Tac/Sir 5 = 104，Tac/ Mtx =107）测量了211例患者血浆样本中的生物标志物。多变量分析显示，第28天致瘤性-2（ST 2）和T细胞免疫球蛋白粘蛋白-3（TIM 3）的高度抑制与2年非复发死亡率相关（分别为P = 0.0050，P = 0.0075）和具有时间依赖性协变量的比例风险模型（校正风险比：2.43 [1.49-3.95]，P =.0038和4.87 [2.53-9.34]，P
A phase 3 clinical trial (BMT CTN 0402) comparing tacrolimus/sirolimus (Tac/Sir) vs tacrolimus/methotrexate (Tac/Mtx) as graft-versus-host disease (GVHD) prophylaxis after matched-related allogeneic hematopoietic cell transplantation (HCT) recently showed no difference between study arms in acute GVHD-free survival. Within this setting of a prospective, multicenter study with uniform GVHD prophylaxis, conditioning regimen, and donor source, we explored the correlation of 10 previously identified biomarkers with clinical outcomes after allogeneic HCT. We measured biomarkers from plasma samples collected in 211 patients using enzyme-linked immunosorbent assay (Tac/Sir5 104, Tac/ Mtx =107). High suppression of tumorigenicity-2 (ST2) and T-cell immunoglobulin mucin-3 (TIM3) at day 28 correlated with 2-year nonrelapse mortality in multivariate analysis (P =.0050, P =.0075, respectively) and in a proportional hazards model with time-dependent covariates (adjusted hazard ratio: 2.43 [1.49-3.95], P =.0038 and 4.87 [2.53-9.34], P