Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Hematopoietic Stem Cell Transplant Unit, Department of Hematology L, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Biol Blood Marrow Transplant. 2018 Mar;24(3):600-607. doi: 10.1016/j.bbmt.2017.10.025. Epub 2017 Oct 23.
Acute graft-versus-host disease (aGVHD) remains a cause of excessive morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Primary treatment consists of high-dose corticosteroids, but a small group of patients develop steroid-refractory disease, and their prognosis is especially poor. There is experimental evidence that coexisting inflammation aggravates aGVHD. Because C-reactive protein (CRP) is a systemic inflammatory marker, we aimed to investigate whether plasma CRP concentrations at the diagnosis of aGVHD can predict the risk of failing first-line therapy and developing steroid-refractory disease. We retrospectively studied 461 patients who underwent HSCT between 2010 and 2015. aGVHD grade II-IV was diagnosed in 148 patients (32%). CRP level and total white blood cell, lymphocyte, and neutrophil counts were available for all patients at the time of aGVHD diagnosis. According to local protocol, patients with failed response to high-dose steroid therapy (2 mg/kg) were treated with the TNF-α inhibitor infliximab and categorized as having steroid-refractory disease. Of 148 patients with grade II-IV aGVHD, 28 (19%) developed steroid-refractory disease. In these patients, plasma CRP concentration at diagnosis ranged between <1 and 253 mg/L. CRP levels were significantly higher in patients who developed steroid-refractory disease compared with those who responded to high-dose corticosteroid therapy (odds ratio, 1.50; 95% confidence interval, 1.18-1.93; P = .001). This translated into significantly increased transplantation-related mortality and decreased overall survival in the patients with high CRP levels. Total white blood cell, lymphocyte, and neutrophil counts were not associated with steroid resistance in the patients with aGVHD. These results suggest that CRP level at diagnosis is a valid predictor of the development of steroid-refractory disease in patients who develop grade II-IV aGVHD after HSCT.
急性移植物抗宿主病（aGVHD）仍然是异基因造血干细胞移植（HSCT）后发病率和死亡率过高的原因。主要治疗方法包括大剂量皮质类固醇，但一小部分患者发生类固醇难治性疾病，其预后尤其差。有实验证据表明，并存的炎症会加重 aGVHD。由于 C 反应蛋白（CRP）是一种全身炎症标志物，我们旨在研究 aGVHD 诊断时的血浆 CRP 浓度是否可以预测一线治疗失败和发生类固醇难治性疾病的风险。我们回顾性研究了 2010 年至 2015 年间接受 HSCT 的 461 名患者。148 名患者（32%）诊断为 II-IV 级 aGVHD。所有患者在 aGVHD 诊断时均有 CRP 水平和总白细胞、淋巴细胞和中性粒细胞计数。根据当地方案，对高剂量类固醇治疗反应失败的患者（2mg/kg）用 TNF-α 抑制剂英夫利昔单抗治疗，并归类为类固醇难治性疾病。在 148 名患有 II-IV 级 aGVHD 的患者中，28 名（19%）发生类固醇难治性疾病。在这些患者中，诊断时的血浆 CRP 浓度范围在<1 至 253mg/L 之间。与对大剂量皮质类固醇治疗有反应的患者相比，发生类固醇难治性疾病的患者 CRP 水平显着更高（优势比，1.50；95%置信区间，1.18-1.93；P=0.001）。这导致 CRP 水平较高的患者移植相关死亡率显着增加，总体生存率降低。白细胞、淋巴细胞和中性粒细胞计数与 aGVHD 患者的类固醇耐药性无关。这些结果表明，HSCT 后发生 II-IV 级 aGVHD 的患者中，诊断时的 CRP 水平是发生类固醇难治性疾病的有效预测指标。
