Kamari-Kany Nakisa, Weischendorff Sarah, Ifversen Marianne, Horan Denise Elbæk, Enevold Christian, Kielsen Katrine, Müller Klaus
Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Institute For Inflammation Research, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Pediatr Blood Cancer. 2025 Nov;72(11):e31995. doi: 10.1002/pbc.31995. Epub 2025 Sep 8.
The suppressor of tumorigenesis 2 (ST2) has emerged as one of the most promising biomarkers for predicting mortality of acute graft-versus-host disease (aGvHD) when measured at the onset of symptoms, but detailed time course studies are needed to understand the potential of ST2 as a risk marker of both aGvHD and chronic graft-versus-host disease (cGvHD), potentially allowing pre-emptive adjustment of immunosuppressive treatment.
We measured ST2 levels in 117 children undergoing standard hematopoietic stem cell transplantation (HSCT) before conditioning and at regular intervals post-HSCT.
ST2 levels were significantly increased from Day +7 in patients developing aGvHD of any grade (no GvHD: 23.6 ng/mL; Grade I: 31.9 ng/mL; Grade II: 33.2 ng/mL; Grade III-IV: 59.1 ng/mL; p < 0.0001) and in patients developing aGvHD with visceral involvement (no GvHD: 23.6 ng/mL; skin only aGvHD: 24.9 ng/mL; GI and/or liver aGvHD: 59.8 ng/mL; p < 0.0001). The association between ST2 levels and aGvHD Grade II-IV was confirmed in a multivariable logistic regression analysis, adjusting for diagnosis, conditioning regimen, and donor type (OR = 1.99 per doubling in ST2, 95% confidence interval [CI] = 1.40-2.92; p = 0.00025). Patients developing cGvHD had significantly higher ST2 levels before conditioning and from Day +21 to Day +180 (all p < 0.05). ST2 levels at Day +90 were significantly associated with later development of cGvHD after adjusting for diagnosis, conditioning regimen, donor type, and prior aGvHD (HR = 2.1 per doubling in ST2, 95% CI = 1.51-2.91, p < 0.0001).
This study confirms ST2 as a biomarker reflecting risk of aGvHD and prognosis in pediatric allogeneic HSCT, and our findings indicate a role of ST2 as an early risk marker of cGvHD.
肿瘤发生抑制因子2（ST2）已成为预测急性移植物抗宿主病（aGvHD）死亡率最有前景的生物标志物之一，在症状出现时进行检测即可，但需要详细的时间进程研究来了解ST2作为aGvHD和慢性移植物抗宿主病（cGvHD）风险标志物的潜力，这可能使免疫抑制治疗得以提前调整。
我们检测了117例接受标准造血干细胞移植（HSCT）的儿童在预处理前及HSCT后定期的ST2水平。
在发生任何级别的aGvHD的患者中，从第7天起ST2水平显著升高（无移植物抗宿主病：23.6 ng/mL；I级：31.9 ng/mL；II级：33.2 ng/mL；III-IV级：59.1 ng/mL；p<0.0001），在发生有内脏受累的aGvHD的患者中也是如此（无移植物抗宿主病：23.6 ng/mL；仅皮肤aGvHD：24.9 ng/mL；胃肠道和/或肝脏aGvHD：59.8 ng/mL；p<0.0001）。在多变量逻辑回归分析中，校正诊断、预处理方案和供体类型后，证实了ST2水平与II-IV级aGvHD之间的关联（ST2每增加一倍，比值比[OR]=1.99，95%置信区间[CI]=1.40-2.92；p=0.00025）。发生cGvHD的患者在预处理前以及从第21天到第180天的ST2水平显著更高（所有p<0.05）。校正诊断、预处理方案、供体类型和既往aGvHD后，第90天的ST2水平与cGvHD的后期发生显著相关（ST2每增加一倍，风险比[HR]=2.1，95%CI=1.51-2.91，p<0.0001）。
本研究证实ST2是反映儿童异基因HSCT中aGvHD风险和预后的生物标志物，我们的研究结果表明ST2作为cGvHD的早期风险标志物具有一定作用。
