Tsukasaki Hikaru, Fujita Kei, Lee Shin, Morishita Tetsuji, Oiwa Kana, Negoro Eiju, Hara Takeshi, Tsurumi Hisashi, Ueda Takanori, Yamauchi Takahiro
Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Department of Hematology, Osu Hospital, Aichi, Japan.
Ann Hematol. 2024 Dec;103(12):5549-5555. doi: 10.1007/s00277-024-06064-5. Epub 2024 Oct 25.
Despite an emphasis on the prognostic impact of serum soluble interleukin-2 receptor (sIL-2R) at diagnosis in patients with diffuse large B-cell lymphoma (DLBCL), whether the prognostic impact of elevated sIL-2R is linear remains unclear. To verify the presence of a non-linear association between sIL-2R level at diagnosis and overall survival (OS) in patients with newly diagnosed DLBCL, we conducted a multi-center, observational retrospective study. Among 488 analyzable patients, Cox proportional hazards modeling identified serum sIL-2R level at diagnosis as an independent predictor of OS. Multivariate Cox hazard modeling with restricted cubic spline model demonstrated that the relationship between serum sIL-2R level and OS was clearly non-linear (P for effect of sIL-2R = 0.002; P for non-linearity = 0.015). Mortality risk increased gradually as sIL-2R levels increased and plateaued at approximately 5,000 U/mL. Segmented regression analysis revealed that the trend in negative prognostic impact from a gradual increase in serum sIL-2R level changed significantly, with a breakpoint at approximately 2,000 U/mL. Multivariate receiver operating characteristic curves showed a significant improvement in prediction ability when serum sIL-2R level was added to the International Prognostic Index (IPI). Serum sIL-2R level at diagnosis was not only a prognostic factor, but also improved predictive accuracy for OS when incorporated with the IPI. However, the negative correlation between increasing sIL-2R and prognosis was non-linear.
尽管在弥漫性大B细胞淋巴瘤（DLBCL）患者的诊断中强调了血清可溶性白细胞介素-2受体（sIL-2R）的预后影响，但sIL-2R升高的预后影响是否呈线性仍不清楚。为了验证新诊断的DLBCL患者诊断时sIL-2R水平与总生存期（OS）之间是否存在非线性关联，我们进行了一项多中心观察性回顾性研究。在488例可分析的患者中，Cox比例风险模型将诊断时的血清sIL-2R水平确定为OS的独立预测因素。采用受限立方样条模型的多变量Cox风险模型表明，血清sIL-2R水平与OS之间的关系明显呈非线性（sIL-2R效应的P值 = 0.002；非线性的P值 = 0.015）。随着sIL-2R水平升高，死亡风险逐渐增加，并在约5000 U/mL时趋于平稳。分段回归分析显示，血清sIL-2R水平逐渐升高所带来的负面预后影响趋势发生了显著变化，在约2000 U/mL处出现一个断点。多变量受试者工作特征曲线显示，将血清sIL-2R水平添加到国际预后指数（IPI）中时，预测能力有显著提高。诊断时的血清sIL-2R水平不仅是一个预后因素，而且与IPI结合时还提高了OS的预测准确性。然而，sIL-2R升高与预后之间的负相关是非线性的。
