Ueda Norihiro, Chihara Dai, Kohno Akio, Tatekawa Shotaro, Ozeki Kazutaka, Watamoto Koichi, Morishita Yoshihisa
Division of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan; Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
Biol Blood Marrow Transplant. 2014 Sep;20(9):1335-40. doi: 10.1016/j.bbmt.2014.04.030. Epub 2014 May 2.
Endothelial cell damage has been reported to be associated with noninfectious transplant-related complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among these, noninfectious transplant-related complications with endothelial cell damage (TRC-EC) include sinusoidal occlusive syndrome, transplant-associated microangiopathy, intestinal transplant-associated microangiopathy, capillary leak syndrome, idiopathic pneumonia syndrome, and diffuse alveolar hemorrhage. Because angiopoietin-2 (ANG2) plays an essential role in the endothelial cell damage of various inflammatory disorders, we hypothesized that ANG2 may also play a critical role in TRC-EC. We retrospectively estimated the incidence of TRC-EC and evaluated the association with ANG2 level at transplant. We studied 153 consecutive adult patients who underwent allo-HSCT at our institution between 2000 and 2012. Median patient age was 49 years (range, 16 to 68 years). With a median follow-up of 55 months, 3-year overall survival for all patients was 55%. The incidence of TRC-EC at day 100 was significantly higher in the high-ANG2 group (≥2000 pg/mL; n = 36) than in the low-ANG2 group (<2000 pg/mL; n = 117) (70% [95% confidence interval {CI}, 55% to 84%] versus 16% [95% CI, 11% to 24%]; P < .001). Multivariate analysis revealed that high ANG2 level at transplant was independently associated with higher risk of TRC-EC (hazard ratio, 6.01; 95% CI, 3.16 to 11.43; P < .001) and shorter overall survival (hazard ratio, 2.23; 95% CI, 1.66 to 4.48; P = .002). These results suggest that ANG2 level at transplant may be a useful marker for predicting the risk of TRC-EC after allo-HSCT. Prospective studies are warranted to validate our results.
据报道，内皮细胞损伤与异基因造血干细胞移植（allo-HSCT）后非感染性移植相关并发症有关。其中，伴有内皮细胞损伤的非感染性移植相关并发症（TRC-EC）包括窦性阻塞综合征、移植相关微血管病、肠道移植相关微血管病、毛细血管渗漏综合征、特发性肺炎综合征和弥漫性肺泡出血。由于血管生成素-2（ANG2）在各种炎症性疾病的内皮细胞损伤中起重要作用，我们推测ANG2在TRC-EC中可能也起关键作用。我们回顾性评估了TRC-EC的发生率，并评估了其与移植时ANG2水平的相关性。我们研究了2000年至2012年间在我们机构接受allo-HSCT的153例连续成年患者。患者中位年龄为49岁（范围16至68岁）。中位随访55个月，所有患者的3年总生存率为55%。高ANG2组（≥2000 pg/mL；n = 36）在第100天时TRC-EC的发生率显著高于低ANG2组（<2000 pg/mL；n = 117）（70% [95%置信区间{CI}，55%至84%] 对16% [95% CI，11%至24%]；P <.001）。多变量分析显示，移植时高ANG2水平与TRC-EC风险较高（风险比，6.01；95% CI，3.16至11.43；P <.001）和总生存期较短（风险比，2.23；95% CI，1.66至4.48；P =.002）独立相关。这些结果表明，移植时的ANG2水平可能是预测allo-HSCT后TRC-EC风险的有用标志物。有必要进行前瞻性研究以验证我们的结果。
