Wang Xin Shelley, Shi Qiuling, Shah Nina D, Heijnen Cobi J, Cohen Evan N, Reuben James M, Orlowski Robert Z, Qazilbash Muzaffar H, Johnson Valen E, Williams Loretta A, Mendoza Tito R, Cleeland Charles S
Authors' Affiliations: Departments of Symptom Research, Stem Cell Transplantation, Hematopathology, Lymphoma/Myeloma, and Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res. 2014 Mar 1;20(5):1366-74. doi: 10.1158/1078-0432.CCR-13-2442. Epub 2014 Jan 14.
Increasing research suggests that inflammation mediates symptom development. In this longitudinal study, we examined inflammatory factors related to the development of high symptom burden during autologous hematopoietic stem cell transplant (AuSCT) for multiple myeloma.
Patients (n = 63) repeatedly reported symptom severity on the MD Anderson Symptom Inventory multiple myeloma module (MDASI-MM) and contributed blood samples periodically for up to 100 days after AuSCT for inflammatory marker assays. The temporal associations between serum inflammatory marker concentrations and symptom severity outcomes were examined by nonlinear mixed-effect modeling.
Fatigue, pain, disturbed sleep, lack of appetite, and drowsiness were consistently the most severe MDASI-MM symptoms during the study. Peak symptom severity occurred on day 8 after AuSCT, during white blood cell count nadir. Patterns of serum interleukin (IL)-6 (peak on day 9) and soluble IL-6 receptor (sIL-6R; nadir on day 8) expression paralleled symptom development over time (both P < 0.0001). By univariate analysis, serum IL-6, sIL-6R, IL-10, C-reactive protein, macrophage inflammatory protein (MIP)-1α, sIL-1R2, sIL-1RA, and soluble tumor necrosis factor receptor 1 were significantly related to the most severe symptoms during the first 30 days after AuSCT (all P < 0.05). By multivariate analysis, IL-6 (estimate = 0.170; P = 0.004) and MIP-1α (estimate = -0.172; P = 0.006) were temporally associated with the severity of the component symptom score.
Systemic inflammatory response was associated with high symptom burden during the acute phase of AuSCT. Additional research is needed to understand how the inflammatory response is mechanistically associated with symptom expression and whether suppression of this response can reduce symptoms without compromising tumor control.
越来越多的研究表明炎症介导症状的发展。在这项纵向研究中,我们检测了与多发性骨髓瘤自体造血干细胞移植(AuSCT)期间高症状负担发展相关的炎症因子。
患者(n = 63)在MD安德森症状评估量表多发性骨髓瘤模块(MDASI-MM)上反复报告症状严重程度,并在AuSCT后长达100天定期提供血样用于炎症标志物检测。通过非线性混合效应模型检查血清炎症标志物浓度与症状严重程度结果之间的时间关联。
在研究期间,疲劳、疼痛、睡眠障碍、食欲不振和嗜睡始终是MDASI-MM中最严重的症状。症状严重程度峰值出现在AuSCT后第8天,即白细胞计数最低点时。血清白细胞介素(IL)-6(第9天达到峰值)和可溶性IL-6受体(sIL-6R;第8天达到最低点)的表达模式随时间与症状发展平行(均P < 0.0001)。单因素分析显示,血清IL-6、sIL-6R、IL-10、C反应蛋白、巨噬细胞炎性蛋白(MIP)-1α、sIL-1R2、sIL-1RA和可溶性肿瘤坏死因子受体1与AuSCT后前30天内最严重的症状显著相关(均P < 0.05)。多因素分析显示,IL-6(估计值 = 0.170;P = 0.004)和MIP-1α(估计值 = -0.172;P = 0.006)与组成症状评分的严重程度在时间上相关。
全身炎症反应与AuSCT急性期的高症状负担相关。需要进一步研究以了解炎症反应与症状表达在机制上是如何关联的,以及抑制这种反应是否可以在不影响肿瘤控制的情况下减轻症状。