血管免疫母细胞性T细胞淋巴瘤患者的临床特点及其预后相关因素分析

Analysis of clinical characteristics and prognosis factors in patients with angioimmunoblastic T-cell lymphoma

目的探讨血管免疫母细胞性T细胞淋巴瘤(AITL)患者的临床特点及预后因素。方法选择2012年1月至12月,空军军医大学第一附属医院收治的44例初诊AITL患者为研究对象。其中,男性患者为36例,女性为8例,年龄为18~78岁,中位年龄为57.5岁。44例AITL患者接受CHOP(环磷酰胺+吡柔比星+长春新碱+泼尼松)方案治疗,其中4例联合应用西达苯胺、硼替佐米,6例接受自体造血干细胞移植(auto-HSCT)。回顾性分析AITL患者的临床特点。采用Kaplan-Meier法绘制接受与未接受auto-HSCT患者的总体生存(OS)曲线。采用Log-rank检验对未接受auto-HSCT患者OS率进行单因素分析,纳入分析的影响因素包括性别、国际预后指数(IPI)评分、外周T细胞淋巴瘤预后指数(PIT)评分、年龄、B症状、皮疹、胸腔/腹腔积液、骨髓受累、白细胞计数(WBC)、血红蛋白(Hb)值、血小板计数、血清乳酸脱氢酶(LDH)水平、铁蛋白水平、β2-微球蛋白(MG)水平。将单因素分析结果中有统计学意义,以及有临床指导意义的影响因素,纳入COX比例风险回归模型进行多因素分析。本研究遵循的程序符合2008及2013年修订版《世界医学会赫尔辛基宣言》的要求。结果①本研究44例AITL患者中,有B症状的患者为34例(77.3%)。Ann Arbor分期为Ⅰ~Ⅱ期的患者为5例(11.4%),Ⅲ~Ⅳ期者为39例(88.6%);美国东部协作肿瘤组体能状况评分(ECOG-PS)<2分者为20例(45.5%),ECOG-PS≥2分者为24例(54.5%);IPI评分系0~1分者为9例(20.5%),2分者为12例(27.2%),3~5分者为23例(52.3%);PIT评分系0分者为10例(22.7%),1分者为5例(11.4%),2分者为12例(27.3%),3~4分者为17例(38.6%)。②本研究44例AITL患者血常规检查结果示,中位WBC为6.2×109/L,中位Hb值为125 g/L,中位血小板计数为163×109/L。中位血清LDH水平为292 U/L,中位铁蛋白水平为171μg/L,中位β2-MG水平为3.8 mg/L。14例(31.8%)患者原发病累及骨髓。免疫组织化学检查结果示,27例(61.4%)患者检测到CD21、CD23、CD35表达呈阳性的滤泡树突状细胞(FDC)。③本研究44例AITL患者完全缓解(CR)率为13.6%(6/44),部分缓解(PR)率为38.7%(17/44),疾病稳定(SD)率为22.7%(10/44),疾病进展(PD)率为25.0%(11/44)。44例患者5年OS率为50.0%,中位OS期为14.5个月(8 d^60.0个月)。④仅接受CHOP方案化疗的AITL患者5年OS率为44.1%;接受CHOP方案联合西达苯胺、硼替佐米等新药治疗的患者5年OS率为75.0%。接受auto-HSCT的AITL患者5年OS率为83.3%,高于未接受auto-HSCT者的22.9%,并且差异有统计学意义(χ2=6.001,P=0.014)。38例未接受auto-HSCT的AITL患者预后相关因素的单因素分析结果显示,年龄≤60岁的患者5年OS率为37.8%,显著高于年龄>60岁者的11.8%,并且差异有统计学意义(χ2=0.139,P=0.023)。血清β2-MG水平<4 mg/L的患者5年OS率为23.9%,显著高于β2-MG水平≥4 mg/L者的18.6%,并且差异亦有统计学意义(χ2=5.520,P=0.019)。⑤对38例未接受auto-HSCT患者预后相关因素进行多因素分析发现,年龄>60岁(HR=2.716,P=0.031),骨髓受累(HR=2.696,P=0.042),血清β2-MG水平≥4 mg/L(HR=4.927,P=0.004)为AITL患者预后的独立危险因素。结论AITL患者以中、老年男性为主,常合并皮疹、浆膜腔积液等,首诊时Ann Arbor分期晚。年龄>60岁、骨髓受累、血清β2-MG水平≥4 mg/L可以作为未接受auto-HSCT AITL患者的预后独立危险因素。西达苯胺、硼替佐米等新药可以提高AITL患者疗效,auto-HSCT能够有效改善患者OS。

Objective To investigate the clinical characteristics and prognostic factors of patients with angioimmunoblastic T-cell lymphoma(AITL).Methods From January to December,2012,a total of 44 AITL patients admitted to Department of Hematology,First Affiliated Hospital of Air Force Medical University were included as study subjects.There were 36 males and 8 females,with age of 18-78 years and median age of 57.5 years.All 44 patients were treated with CHOP(cyclophosphamide+pirarubicin+vincristine+prednisone)regimen,4 of them were combined with chidamide or bortezomib,6 of them were combined with autologous hematopoietic stem cell transplantation(auto-HSCT).Clinical characteristics of AITL patients were retrospectively analyzed.Kaplan-Meier method was used to map overall survival(OS)curves of patients treated with and without auto-HSCT.And univariate analysis of OS rate was performed in patients treated without auto-HSCT using Log-rank test.Influencing factors included gender,age,International Prognostic Index(IPI)score,Prognostic Index for peripheral T-cell lymphoma(PIT)score,B symptoms,skin rashes,chest/abdominal cavity effusion,bone marrow involvement,white blood cell count(WBC),hemoglobin(Hb)value,platelet count,serum lactate dehydrogenase(LDH)level,ferritin level,β2-microglobulin(MG)level.Factors with statistical significance in univariate analysis and clinical guiding significance were included in COX proportional hazards regression model for multivariate analysis.The procedure of this study was accordance with the requirement of the revised World Medical Association Declaration of Helsinki in 2008 and 2013.Results①Among 44 AITL patients,34 cases(77.3%)had B symptoms.Five cases(11.4%)were Ann ArborⅠ-Ⅱstage,39 cases(88.6%)wereⅢ-Ⅳstage.Twenty cases(45.5%)had Eastern Cooperative Oncology Group,performance status(ECOG-PS)score<2,24 cases(54.5%)had ECOG-PS score≥2.Nine cases(20.5%)had IPI score of 0-1,12 cases(27.2%)had score of 2,23 cases(52.3%)had score of 3-5.Ten cases(22.7%)had PIT score of 0,5 cases(11.4%)had score of 1,12 cases(27.3%)had score of 2,and 17 cases(38.6%)had score of 3-4.②Blood routine test of 44 cases of AITL patients showed that median WBC was 6.2×109/L,median Hb value was 125 g/L,and median platelet count was 163×109/L.Median serum LDH level was 292 U/L,median ferritin level was 171μg/L,and medianβ2-MG level was 3.8 mg/L.Bone marrow was involved by lesion in 14 cases(31.8%).Results of immunohistochemistry showed that follicular dendritic cell(FDC)with positive CD21,CD23,and CD35 expression was detected in 27 patients(61.4%).③Complete remission(CR)rate of 44 AITL patients was 13.6%(6/44),partial remission(PR)rate was 38.7%(17/44),stable disease(SD)rate was 22.7%(10/44),progressive disease(PD)rate was 25.0%(11/44).The 5-year OS rate was 50.0%,and the median OS time was 14.5 months(8 d-60.0 months).④The 5-year OS rate of patients who only received CHOP regimen chemotherapy was 44.1%,and patients who treated combined with new drugs(chidamide or bortezomib)was 75.0%.The 5-year OS rate of AITL patients receiving auto-HSCT was 83.3%,and was higher than that of 22.9%patients who didn′t receive auto-HSCT,and the difference was statistically significant(χ2=6.001,P=0.014).Univariate analysis of prognostic factors in 38 AITL patients treated without auto-HSCT showed that the 5-year OS rate was 37.8%in patients aged≤60 years,and significantly higher than that of 11.8%in patients aged>60 years,and the difference was statistically significant(χ2=0.139,P=0.023).The 5-year OS rate in patients with serumβ2-MG level<4 mg/L was 23.9%,and significantly higher than that of 18.6%in patients with serumβ2-MG level≥4 mg/L,and the difference was also statistically significant(χ2=5.520,P=0.019).⑤Multivariate analysis of prognostic factors in 38 patients treated without auto-HSCT showed that age>60 years(HR=2.716,P=0.031),bone marrow involvement(HR=2.696,P=0.042),serumβ2-MG level≥4 mg/L(HR=4.927,P=0.004)were independent risk factors for AITL prognosis.Conclusions Majority of AITL patients are middle-aged and elderly males,often accompanied by skin rash and serous effusion.The disease was first diagnosed late-stage in Ann Arbor.Age>60 years,bone marrow involvement and serumβ2-MG level≥4 mg/L,can be used as independent indicators of poor prognosis of patients treated without auto-HSCT.New drugs such as chidamide and bortezomib could improve curative effect of AITL patients.auto-HSCT coukl effectively improve the OS of patients.