Artz Andrew S, Wickrema Amittha, Dinner Shira, Godley Lucy A, Kocherginsky Masha, Odenike Olatoyosi, Rich Elizabeth S, Stock Wendy, Ulaszek Jodie, Larson Richard A, van Besien Koen
Section of Hematology/Oncology, Department of Medicine, University of Chicago, The University of Chicago Cancer Research Center, Chicago, Illinois 60637, USA.
Biol Blood Marrow Transplant. 2008 Nov;14(11):1209-16. doi: 10.1016/j.bbmt.2008.08.004.
We tested the independent prognostic impact of 2 commonly used biomarkers, C-reactive protein (CRP) and interleukin (IL)-6, on the outcomes of allogeneic hematopoietic cell transplantation (HCT). Consecutive patients who underwent a uniform reduced-intensity conditioning (RIC) regimen of fludarabine (Flu), melphalan (Mel), and alemtuzumab were evaluated retrospectively. Cryopreserved serum samples drawn before the RIC were available to measure CRP levels in 81 patients and IL-6 levels in 79 patients. Patients with CRP levels above the median of 18.5 mg/L had significantly more grade 3-4 hepatic toxicity (P=.01), longer HCT hospital stay (P=.005), more acute graft-versus-host disease (aGVHD) (P=.003), greater nonrelapse mortality (NRM) (P=.01), and inferior overall survival (OS; P=.02). Higher baseline CRP showed no significant correlation with grade 3-4 infectious toxicity (P=.09). In contrast to CRP, pre-HCT IL-6 levels above the median of 78.3 pg/mL did not confer a statistically significant increased risk of toxicity or mortality. An elevated HCT comorbidity index (HCT-CI) did not predict for any measure of HCT morbidity. After adjustment for disease status, comorbidity, performance status, and age, elevated CRP concentration remained predictive of NRM. These data require confirmation in non-T cell-depleted conditioning regimens. If validated, they suggest that preconditioning CRP holds promise for enhancing estimates of transplantation tolerance.
我们测试了两种常用生物标志物——C反应蛋白(CRP)和白细胞介素(IL)-6对异基因造血细胞移植(HCT)结局的独立预后影响。对接受氟达拉滨(Flu)、美法仑(Mel)和阿仑单抗统一减低强度预处理(RIC)方案的连续患者进行回顾性评估。在RIC之前采集的冷冻保存血清样本可用于测量81例患者的CRP水平和79例患者的IL-6水平。CRP水平高于中位数18.5mg/L的患者有显著更多的3-4级肝毒性(P = 0.01)、更长的HCT住院时间(P = 0.005)、更多的急性移植物抗宿主病(aGVHD)(P = 0.003)、更高的非复发死亡率(NRM)(P = 0.01)以及更差的总生存期(OS;P = 0.02)。较高的基线CRP与3-4级感染毒性无显著相关性(P = 0.09)。与CRP相反,HCT前IL-6水平高于中位数78.3pg/mL并未导致毒性或死亡率的统计学显著增加风险。升高的HCT合并症指数(HCT-CI)不能预测任何HCT发病率指标。在对疾病状态、合并症、体能状态和年龄进行调整后,升高的CRP浓度仍然是NRM的预测指标。这些数据需要在非T细胞去除预处理方案中得到证实。如果得到验证,它们表明预处理CRP有望提高对移植耐受性的评估。