Clinical Research Division, Fred Hutchinson Cancer Research Center and University of Washington Medical Center, 1100Fairview Ave. N, Seattle, WA 98109, USA.
Biol Blood Marrow Transplant. 2011 Nov;17(11):1594-601. doi: 10.1016/j.bbmt.2011.07.021. Epub 2011 Jul 30.
Biomarkers capable of predicting the onset and severity of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HCT) would enable preemptive and risk-stratified therapy. Severe aGVHD leads to gastrointestinal protein loss, resulting in hypoalbuminemia. We hypothesized that decreases in serum albumin at onset of aGVHD would predict the risk of progression to severe aGVHD. We identified 401 patients who developed aGVHD grades II-IV after reduced-intensity allogeneic HCT and reviewed all available serum albumin values from 30 days before HCT to 45 days after initiation of treatment for aGVHD. A ≥0.5 g/dL decrease in serum albumin concentration from pretransplantation baseline to the onset of treatment for aGVHD predicted the subsequent development of grade III/IV aGVHD (versus grade II aGVHD) with a sensitivity of 69% and a specificity of 73%. Overall mortality at 6 months after initiation of aGVHD treatment was 36% versus 17% for patients with and without ≥0.5 g/dL decreases in serum albumin, respectively (P = .0009). We conclude that change in serum albumin concentration from baseline to initiation of aGVHD treatment is an inexpensive, readily available, and predictive biomarker of GVHD severity and mortality after reduced-intensity allogeneic HCT.
生物标志物能够预测异基因造血细胞移植(HCT)后急性移植物抗宿主病(aGVHD)的发作和严重程度,从而实现预防性和风险分层治疗。严重的 aGVHD 会导致胃肠道蛋白质丢失,导致低白蛋白血症。我们假设 aGVHD 发作时血清白蛋白的降低将预测发展为严重 aGVHD 的风险。我们确定了 401 名接受减强度异基因 HCT 后发生 II-IV 级 aGVHD 的患者,并回顾了 HCT 前 30 天至开始治疗 aGVHD 后 45 天所有可用的血清白蛋白值。与发生 II 级 aGVHD 相比,从移植前基线到开始治疗 aGVHD 时血清白蛋白浓度降低≥0.5 g/dL 预测随后发生 III/IV 级 aGVHD 的敏感性为 69%,特异性为 73%。开始治疗 aGVHD 后 6 个月的总死亡率分别为 36%和 17%,对于发生和未发生血清白蛋白降低≥0.5 g/dL 的患者分别为(P =.0009)。我们得出结论,从基线到开始治疗 aGVHD 时血清白蛋白浓度的变化是异基因 HCT 后评估 GVHD 严重程度和死亡率的一种廉价、易于获得且具有预测价值的生物标志物。