Takemura Kazuya, Nakamae Mika, Okamura Hiroshi, Sakatoku Kazuki, Ido Kentaro, Makuuchi Yosuke, Kuno Masatomo, Takakuwa Teruhito, Hirose Asao, Nishimoto Mitsutaka, Nakashima Yasuhiro, Koh Hideo, Igarashi Koji, Kubota Hiroshi, Hino Masayuki, Nakamae Hirohisa
Department of Central Clinical Laboratory, Osaka Metropolitan University Hospital, Osaka, Japan.
Department of Hematology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Ann Hematol. 2024 May;103(5):1705-1715. doi: 10.1007/s00277-024-05685-0. Epub 2024 Mar 18.
Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT), and stratification of the high-risk group before transplantation is significant. Serum autotaxin (ATX) levels have been reported to increase in patients with liver fibrosis caused by metabolic inhibition from liver sinusoidal endothelial cells. Considering that the pathophysiology of VOD/SOS begins with liver sinusoidal endothelial cell injury, an increase in serum ATX levels may precede the onset of VOD/SOS. A retrospective study with 252 patients, including 12 patients with VOD/SOS, who had received allo-HCT was performed. The cumulative incidence of VOD/SOS was higher in the group with serum ATX levels before conditioning (baseline ATX) above the upper reference limit (high ATX group, p < 0.001), and 1-year cumulative incidences were 22.7% (95% confidence interval [95%CI], 3.1-42.4%) and 3.5% (95%CI, 1.1-5.8%), respectively. In the multivariate analysis, elevated baseline ATX was identified as an independent risk factor for VOD/SOS development and showed an additive effect on the predictive ability of known risk factors. Furthermore, the incidence of VOD/SOS-related mortality was greater in the high ATX group (16.7% vs. 1.3%; p = 0.005). Serum ATX is a potential predictive marker for the development of VOD/SOS.
静脉闭塞性疾病/肝窦阻塞综合征(VOD/SOS)是异基因造血细胞移植(allo-HCT)后一种危及生命的并发症,移植前对高危组进行分层具有重要意义。据报道,在因肝窦内皮细胞代谢抑制导致肝纤维化的患者中,血清自分泌运动因子(ATX)水平会升高。鉴于VOD/SOS的病理生理学始于肝窦内皮细胞损伤,血清ATX水平升高可能先于VOD/SOS的发病。对252例接受allo-HCT的患者进行了一项回顾性研究,其中包括12例VOD/SOS患者。预处理前血清ATX水平高于参考上限的组(高ATX组,p<0.001)中VOD/SOS的累积发生率更高,1年累积发生率分别为22.7%(95%置信区间[95%CI],3.1-42.4%)和3.5%(95%CI,1.1-5.8%)。在多变量分析中,基线ATX升高被确定为VOD/SOS发生的独立危险因素,并且对已知危险因素的预测能力具有累加效应。此外,高ATX组中VOD/SOS相关死亡率更高(16.7%对1.3%;p=0.005)。血清ATX是VOD/SOS发生的潜在预测标志物。