Lu Yaxiao, Yu Jingwei, Gong Wenchen, Su Liping, Sun Xiuhua, Bai Ou, Zhou Hui, Guan Xue, Zhang Tingting, Li Lanfang, Qiu Lihua, Qian Zhengzi, Zhou Shiyong, Meng Bin, Ren Xiubao, Wang Xianhuo, Zhang Huilai
Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China.
Departments of Pathology and Immunology/Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Front Oncol. 2021 Jul 13;11:708784. doi: 10.3389/fonc.2021.708784. eCollection 2021.
Although the role of tumor-infiltrating T cells in follicular lymphoma (FL) has been reported previously, the prognostic value of peripheral blood T lymphocyte subsets has not been systematically assessed. Thus, we aim to incorporate T-cell subsets with clinical features to develop a predictive model of clinical outcome.
We retrospectively screened a total of 1,008 patients, including 252 newly diagnosed FL patients with available peripheral blood T lymphocyte subsets who were randomized to different sets (177 in the training set and 75 in the internal validation set). A nomogram and a novel immune-clinical prognostic index (ICPI) were established according to multivariate Cox regression analysis for progression-free survival (PFS). The concordance index (C-index), Akaike's information criterion (AIC), and likelihood ratio chi-square were employed to compare the ICPI's discriminatory capability and homogeneity to that of FLIPI, FLIPI2, and PRIMA-PI. Additional external validation was performed using a dataset (n = 157) from other four centers.
In the training set, multivariate analysis identified five independent prognostic factors (Stage III/IV disease, elevated lactate dehydrogenase (LDH), Hb <120g/L, CD4+ <30.7% and CD8+ >36.6%) for PFS. A novel ICPI was established according to the number of risk factors and stratify patients into 3 risk groups: high, intermediate, and low-risk with 4-5, 2-3, 0-1 risk factors respectively. The hazard ratios for patients in the high and intermediate-risk groups than those in the low-risk were 27.640 and 2.758. The ICPI could stratify patients into different risk groups both in the training set (P < 0.0001), internal validation set (P = 0.0039) and external validation set (P = 0.04). Moreover, in patients treated with RCHOP-like therapy, the ICPI was also predictive (P < 0.0001). In comparison to FLIPI, FLIPI2, and PRIMA-PI (C-index, 0.613-0.647), the ICPI offered adequate discrimination capability with C-index values of 0.679. Additionally, it exhibits good performance based on the lowest AIC and highest likelihood ratio chi-square score.
The ICPI is a novel predictive model with improved prognostic performance for patients with FL treated with R-CHOP/CHOP chemotherapy. It is capable to be used in routine practice and guides individualized precision therapy.
尽管先前已报道肿瘤浸润性T细胞在滤泡性淋巴瘤（FL）中的作用，但外周血T淋巴细胞亚群的预后价值尚未得到系统评估。因此，我们旨在将T细胞亚群与临床特征相结合，以建立临床结局预测模型。
我们回顾性筛选了总共1008例患者，其中包括252例新诊断的FL患者，这些患者具有可用的外周血T淋巴细胞亚群，并被随机分为不同组（训练组177例，内部验证组75例）。根据多因素Cox回归分析无进展生存期（PFS），建立了列线图和新的免疫临床预后指数（ICPI）。采用一致性指数（C指数）、赤池信息准则（AIC）和似然比卡方检验，比较ICPI与FLIPI、FLIPI2和PRIMA-PI的鉴别能力和同质性。使用来自其他四个中心的数据集（n = 157）进行额外的外部验证。
在训练组中，多因素分析确定了PFS的五个独立预后因素（III/IV期疾病、乳酸脱氢酶（LDH）升高、血红蛋白<120g/L、CD4+<30.7%和CD8+>36.6%）。根据危险因素数量建立了新的ICPI，并将患者分为3个风险组：高、中、低风险组，分别有4 - 5个、2 - 3个、0 - 1个危险因素。高风险组和中风险组患者的风险比分别是低风险组患者的27.640倍和2.758倍。ICPI在训练组（P < 0.0001）、内部验证组（P = 0.0039）和外部验证组（P = 0.04）中均能将患者分为不同风险组。此外，在接受RCHOP样治疗的患者中，ICPI也具有预测性（P < 0.0001）。与FLIPI、FLIPI2和PRIMA-PI（C指数，0.613 - 0.647）相比，ICPI具有足够的鉴别能力，C指数值为0.679。此外，基于最低的AIC和最高的似然比卡方评分，它表现出良好的性能。
ICPI是一种新型预测模型，对接受R-CHOP/CHOP化疗的FL患者具有更好的预后性能。它能够用于常规实践并指导个体化精准治疗。
