外周血CD4^+T淋巴细胞绝对数及CD4^+/CD8^+比值在套细胞淋巴瘤中的预后价值

Prognostic value of absolute CD4^+ T cell counts and CD4^+/CD8^+ ratio in peripheral blood of patients with mantle cell lymphoma

目的:探索外周血T淋巴细胞亚群计数在套细胞淋巴瘤(mantle cell lymphoma,MCL)患者中的分布、与临床特征的相关性及预后价值。方法:回顾性分析2006—2017年92例初诊MCL患者的临床资料。使用简化的MCL国际预后指数(s MI-PI)进行预后评分,采用流式细胞术分析T淋巴细胞亚群计数,包括CD4^+T淋巴细胞绝对数(ACD4C)和CD8^+T淋巴细胞绝对数(ACD8C)。Mann-Whitney U及Kruskal-Wallis检验分析T淋巴细胞亚群计数与其他临床指标的相关性。采用Kaplan-Meier法进行生存分析,Cox比例风险模型进行预后因素分析。结果:中位随访51个月(12～150个月),92例患者的中位总生存期(OS)是44个月。1年、3年、5年OS率分别为72%、45%、37%。ACD4C>0.5×10~9个/L的患者较ACD4C≤0.5×10~9个/L的患者的无进展生存期(PFS)和OS更长(P=0.009和P=0.004)。CD4^+/CD8^+比值>1.2的患者较≤1.2的患者有更长的PFS和OS(P=0.025和P=0.009)。单变量Cox回归分析显示:体力状态(ECOG评分)≥2分(P=0.021)、B症状(发热、盗汗或体重下降)(P=0.001)、升高的血清乳酸脱氢酶(LDH)(P=0.027)、高s MIPI评分(P=0.004)、低ACD4C(P=0.013)、低CD4^+/CD8^+比值(P=0.030)与较短的PFS相关。而较短的OS与B症状(P<0.001)、高s MIPI评分(P=0.004)、升高的LDH(P=0.040)、低ACD4C(P=0.006)和低CD4^+/CD8^+比值(P=0.012)相关。多因素Cox回归分析显示:B症状(P=0.006)、低ACD4C(P=0.001)是影响PFS的独立预后因素;B症状(P=0.003)、高sMIPI评分(P=0.047)、低ACD4C(P=0.001)、低CD4^+/CD8^+比值(P=0.031)是影响OS独立的预后因素。结论:低ACD4C、低CD4^+/CD8^+比值与MCL患者不良的预后相关,ACD4C水平、CD4^+/CD8^+比值可作为判断MCL患者预后方便且有效的指标。

Objective:To explore the distribution of T lymphocyte subsets in peripheral blood of patients with mantle cell lymphoma(MCL),and evaluate correlation with clinical baseline characteristics and its prognostic value.Methods:The clinical data of 92 newly diagnosed MCL patients from 2006 to 2017 were analyzed retrospectively.The prognostic stratification was performed using a simplified MCL international prognostic index s MIPI.The T lymphocyte subsets,including the absolute number of CD4^+T lymphocytes(ACD4C)and the absolute number of CD8^+T lymphocytes(ACD8C)were analyzed by flow cytometry.Comparisons of T lymphocyte subsets as continuous parameters in different groups were described using Mann-Whitney U test and Kruskal-Wallis.Kaplan-Meier method was used to survival analysis,and the Cox proportional hazards models were used for the estimation of prognostic factors.Results:The median follow-up was 51 months(12-150 months),and the median overall survival(OS)in 92 patients was 44 months.The OS rate at 1,3 and 5 years was 72%,45%and 37%,respectively.In our cohort,patients with high ACD4C(>0.5×10^9/L)had longer PFS and OS(P=0.009,P=0.004),while patients with low CD4^+/CD8^+ratio(≤1.2)had unfavorable PFS and OS(P=0.025,P=0.009).Univariate Cox regression indicated that ECOG≥2(P=0.021),B symptoms(fever,night sweats or weight loss)(P=0.001),elevated LDH(P=0.027),high s MIPI score(P=0.004),low ACD4C(P=0.013)and low CD4^+/CD8^+ratio(P=0.030)correlated with shorter PFS,while the inferior OS was associated with B symptoms(P<0.001),high sMIPI score(P=0.004),elevated LDH(P=0.040),low ACD4C(P=0.006)and low CD4^+/CD8^+ratio(P=0.012).Multivariate Cox regression showed that B symptoms(P=0.006)and low ACD4C(P=0.001)were the independent prognostic factors of PFS;B symptoms(P=0.003),high sMIPI score(P=0.047),low ACD4C(P=0.001),low CD4^+/CD8^+ratio(P=0.031)were the independent prognostic factors of OS.Conclusion:Low ACD4C and low CD4^+/CD8^+ratio were associated with unfavorable prognosis in MCL patients.ACD4C level and CD4^+/CD8^+ratio proved to be convenient and effective predictors of prognosis in patients with MCL.