摘要
背景与目的:在套细胞淋巴瘤(mantle cell lymphoma,MCL)中,骨髓侵犯十分常见。目前骨髓活检(bone marrow biopsy,BMB)仍是判断淋巴瘤患者骨髓侵犯的金标准,但易出现假阴性结果且会增加患者的痛苦。同时,骨髓侵犯在MCL中的预后预测价值也不明确。因此,本研究旨在研究流式细胞术(flow cytometry,FCM)在MCL骨髓侵犯诊断及预后评估中的应用价值,并进一步探讨骨髓侵犯状态对MCL患者预后的影响。方法:收集2010年1月—2024年4月在郑州大学第一附属医院初治的MCL患者的病历资料,对其中具有治疗前^(18)F-氟代脱氧葡萄糖正电子发射断层显像/计算机断层扫描(^(18)Ffluorodeoxyglucose positron emission tomography/computed tomography,^(18)F-FDG PET/CT)、骨髓穿刺及活检结果和有效随访数据的患者进行回顾性队列研究。通过受试者工作特征(receiver operating characteristic,ROC)曲线分析确定骨髓FC阳性的判断阈值,采用配对χ^(2)检验进行灵敏度和特异度分析,采用Kaplan-Meier法进行生存分析,采用COX回归模型分析影响无进展生存期(progression-free survival,PFS)、总生存期(overall survival,OS)的独立预后危险因素,采用列线图构建预后模型并通过ROC曲线、校准曲线及限制性立方样条(restricted cubic spline,RCS)进行验证。结果:共97例患者纳入本研究。利用FCM检测的不同淋巴瘤细胞比例与BMB结果进行拟合绘制ROC曲线,确定骨髓FCM中的淋巴瘤细胞比例>5.31%为骨髓FCM阳性的判断阈值。以此为标准,FCM检测骨髓侵犯的灵敏度为93.3%(42/45),特异度为73.1%(38/52),阳性预测值为75.0%(42/56),阴性预测值为92.7%(38/41)。Kaplan-Meier生存分析结果显示,基于BMB、^(18)F-FDG PET/CT及FCM判定的骨髓侵犯阳性与否,对患者PFS(P=0.956、0.964、0.748)及OS(P=0.900、0.852、0.145)均无显著影响,而骨髓FCM中的淋巴瘤细胞比例≥30.0%组的PFS和OS均显著短于对照组(2年PFS率:42.4%vs 62.5%,P=0.010;2年OS率:63.6%vs 82.8%,P=0.011)。多因素回归分析显示,年龄、套细胞淋巴瘤国际预后指数(mantle cell lymphoma international prognostic index,MIPI)评分≥6分、MCL分型均为MCL患者PFS、OS的独立预后危险因素,而骨髓FCM中的淋巴瘤细胞比例≥30%仅为PFS的独立预后危险因素(P均<0.05)。进一步将上述潜在预后危险因素纳入构建PFS风险预测模型,结果显示,年龄、MIPI评分、MCL病理学分型及骨髓淋巴瘤细胞比例在模型中均表现出优异的预测效能。从多维度对预测模型及骨髓淋巴瘤细胞比例的临床价值进行验证后展现出与研究结果良好的一致性。结论:采用传统定性方法判定的骨髓侵犯状态对MCL患者的预后无显著影响;而骨髓FCM检测的淋巴瘤细胞比例在诊断骨髓侵犯和预后评估中均展现出良好的效能。将该指标纳入预后模型并校正其他混杂因素后,仍保持稳定且优异的预测性能,提示其具备精准、客观的临床应用价值。
Background and purpose:In mantle cell lymphoma(MCL),bone marrow involvement is prevalent.Currently,bone marrow biopsy(BMB)is considered the gold standard for detecting bone marrow involvement.However,BMB is associated with a high risk of false-negative results and can cause discomfort and pain.Meanwhile,the prognostic value of bone marrow involvement remains ambiguous.Therefore,this research aims to explore the clinical significance of flow cytometry(FCM)in the diagnosis of bone marrow involvement and prognostic evaluation of MCL,and further investigate the association between bone marrow involvement and the prognosis.Methods:A retrospective analysis was conducted on patients with newly diagnosed MCL who were treated at the First Affiliated Hospital of Zhengzhou University from January 2010 to April 2024.Among them,patients had pre-treatment ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT),bone marrow examination results as well as effective follow-up data.Receiver operating characteristic(ROC)curve analysis was conducted to determine the optimal diagnostic threshold for FCM positive,pairedχ^(2) test was employed to analyze the sensitivity and specificity,survival analysis was performed using the Kaplan-Meier method,and independent prognostic risk factors affecting progression-free survival(PFS)and overall survival(OS)were analyzed using the COX regression model.A nomogram was constructed to predict prognosis and was verified using ROC curves,calibration curves,and restricted cubic splines(RCS).Results:A total of 97 patients were enrolled in this study.The various ratios of lymphoma cells detected by FCM were fitted with BMB results to construct the ROC curve.Through this analysis,a ratio of lymphoma cells>5.31%was determined as the threshold to define the FCM positive.Based on this standard,the sensitivity of FCM increased to 93.3%(42/45),and the specificity was 73.1%(38/52).The positive predictive value(PPV)was 75.0%(42/56),and the negative predictive value(NPV)was 92.7%(38/41).Whether bone marrow involvement was positive or negative,as determined by BMB,PET/CT and FCM,there was no significant impact on the PFS(0.956,0.964 and 0.748 respectively)and OS(0.900,0.852 and 0.145 respectively)of patients.The PFS and OS rates for the group with a ratio of lymphoma cells≥30.0%were significantly shorter compared to those in the control group(2-year PFS rate:42.4%vs 62.5%,P=0.010;2-year OS rate:63.6%vs 82.8%,P=0.011).Multivariate analysis showed that age,mantle cell lymphoma international prognostic index(MIPI)score≥6 and morphological variants were independent prognostic risk factors for PFS and OS(All P<0.05),and a ratio of lymphoma cells≥30%was solely an independent prognostic risk factor for PFS.The PFS risk prediction model was constructed by incorporating collected potential prognostic variables.The results indicated that age,MIPI score,MCL pathological classification,and the ratio of lymphoma cells all demonstrated excellent predictive performance within the model.Subsequent multi-dimensional validation of the predictive model and the clinical significance of the ratio of lymphoma cells in bone marrow fluid revealed a strong alignment with the research findings.Conclusion:In MCL,conventional qualitative assessments of bone marrow involvement have no impact on survival prognosis.The ratio of lymphoma cells in bone marrow fluid exhibits considerable clinical utility in both the diagnosis of bone marrow involvement and the assessment of prognosis,and it retains stable and robust predictive performance when incorporated into the prognostic model and adjusted for other confounding variables,indicating its precise,objective clinical utility.
作者
王迪
李梦涵
吴皓辰
孙金淼
谢紫腾
李继伟
张蕾
张明智
常宇
WANG Di;LI Menghan;WU Haochen;SUN Jinmiao;XIE Ziteng;LI Jiwei;ZHANG Lei;ZHANG Mingzhi;CHANG Yu(Department of Oncology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,Henan Province,China)
出处
《中国癌症杂志》
北大核心
2026年第1期67-76,共10页
China Oncology
