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移植期循环 IL-17 水平可预测清髓性异基因干细胞移植后早期白血病复发。

Circulating IL-17 levels during the peri-transplant period as a predictor for early leukemia relapse after myeloablative allogeneic stem cell transplantation.

机构信息

Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul, South Korea.

出版信息

Ann Hematol. 2012 Mar;91(3):439-48. doi: 10.1007/s00277-011-1318-9. Epub 2011 Sep 6.

Abstract

IL-17 is involved in inducing and mediating pro-inflammatory responses. The association of IL-17 with tumor growth or graft-versus-host disease (GVHD) has become a subject of controversy. We hypothesized that serum IL-17 (sIL-17) levels during the peri-transplant period may affect alloreactive responses after allogeneic stem cell transplantation (SCT). sIL-17 levels of 95 patients with leukemia who had undergone myeloablative allogeneic SCT were measured using ELISA before conditioning and on day 0, +7, and +14 after transplantation. With a median follow-up of 17 months, the overall survival, disease-free survival, non-relapse mortality, and relapse incidence were 70.9%, 66.3%, 10.3%, and 23.4%, respectively. Ten patients relapsed within 180 days (early relapse, 10.5%) post-transplant. The cumulative incidence of acute GVHD over grade II and chronic GVHD was 55.8% and 69.0%, respectively. Analyses using repeated measures of ANOVA and mean values of sIL-17 revealed that patients relapsed within 180 days had higher sIL-17 levels, whereas no association existed between sIL-17 levels and other clinical outcomes, including acute GVHD. Receiver operating characteristic curve analyses also revealed that sIL-17 levels were available for the prediction of early relapse and that patients with higher sIL-17 levels at each time point had a significantly higher early relapse. Multivariate analyses and subgroup analyses with only standard disease status suggest the association of sIL-17 levels with subsequent early relapse independent of disease status at transplantation. This study is the first one demonstrating the early change in sIL-17 during the peri-transplant period and the association with early relapse in humans.

摘要

IL-17 参与诱导和介导促炎反应。IL-17 与肿瘤生长或移植物抗宿主病 (GVHD) 的关联已成为争议的主题。我们假设移植期间的血清 IL-17 (sIL-17) 水平可能会影响异基因干细胞移植 (SCT) 后的同种反应。使用 ELISA 测量了 95 例接受清髓性异基因 SCT 的白血病患者在预处理前和移植后第 0、+7 和+14 天的 sIL-17 水平。中位随访 17 个月后,总生存率、无病生存率、非复发死亡率和复发率分别为 70.9%、66.3%、10.3%和 23.4%。10 例患者在移植后 180 天内(早期复发,10.5%)复发。Ⅱ级以上急性 GVHD和慢性 GVHD 的累积发生率分别为 55.8%和 69.0%。使用重复测量方差分析和 sIL-17 的平均值进行分析表明,180 天内复发的患者 sIL-17 水平较高,而 sIL-17 水平与其他临床结局(包括急性 GVHD)之间没有关联。受试者工作特征曲线分析还表明,sIL-17 水平可用于预测早期复发,并且每个时间点 sIL-17 水平较高的患者早期复发的风险显著更高。多变量分析和仅标准疾病状态的亚组分析表明,sIL-17 水平与移植时疾病状态无关,与随后的早期复发有关。这项研究首次证明了移植期间 sIL-17 的早期变化与人类的早期复发有关。

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