CD5和B细胞淋巴瘤/白血病蛋白-2对老年弥漫大B细胞淋巴瘤患者预后的影响

目的探讨CD5和B细胞淋巴瘤/白血病蛋白-2(Bcl-2)对老年弥漫大B细胞淋巴瘤(DLBCL)患者预后的影响。方法回顾性分析2007年1月至2013年12月空军军医大学西京医院血液内科被诊断为DLBCL、年龄60岁的患者35例,对入选患者进行2年随访。收集入选患者临床病理资料及治疗预后信息,免疫组织化学检测CD5、Bcl-2表达,并分别根据CD5、Bcl-2是否为阳性表达(以肿瘤细胞染色阳性30%)、中枢神经累及与否以及肿瘤临床分期对患者进行分组,并比较各组患者间生存情况。采用SPSS 22.0统计软件对数进行分析。组间比较采用Fisher精确检验法。应用Kaplan-Meier法绘制生存曲线,Log-Rank法进行曲线间单因素分析;多因素分析采用Cox回归模型。结果研究最终有3例失访,失访率8.6%。入选患者CD5阳性率为21.9%(7/32),Bcl-2阳性率为46.9%(15/32),CD5及Bcl-2共阳性15.6%(5/32)。21.9%(7/32)患者出现中枢累及。10例患者为肿瘤临床Ⅲ期,22例为临床Ⅳ期。患者中位总生存期(OS)为24个月,中位无进展生存期(PFS)为18个月。1年生存率为96.9%(31/32),2年生存率为71.9%(23/32)。单因素分析显示,与CD5-和Bcl-2~-患者比较,CD5~+和Bcl-2~+患者OS和PFS均较低(P0.05);临床Ⅲ期及Ⅳ期患者PFS(P=0.055)及OS(P=0.076)比较差异均无统计学意义;与无中枢累及患者相比,中枢累及患者OS和PFS较低(均为P=0.004)。另外,CD5~+患者中枢累及率显著大于CD5-患者(57.1%vs 12.0%;P=0.026),Bcl-2~+患者中枢累及率显著大于Bcl-2~-患者(40.0%vs 5.9%;P=0.033),差异均有统计学意义。多因素Cox分析显示,CD5阳性为影响DLBCL患者OS的独立危险因素(OR=11.205,95%CI1.717~73.112;P=0.012)。结论 CD5阳性表达可作为影响老年DLBCL患者预后不良的独立危险因素,对预后判断和未来治疗策略的选择具有重要的临床价值。     

弥漫大B细胞淋巴瘤的预后及分层治疗

弥漫大 B 细胞淋巴瘤（DLBCL）是最常见的非霍奇金淋巴瘤（NHL）,占成人 NHL 的30％～40％。尽管淋巴瘤的治疗已经有很大的进步,仍然有40％的 DLBCL患者死于疾病复发。随着对 DLBCL 临床、病理及分子病理研究的深入,新药物引入 DLBCL 的治疗,需要大样本的随机临床研究来评估新方案的疗效。目前国际预后指数（IPI,表1）已经不能满足临床预后评估。我们将近年来新的对临床及预后有重要影响的预后因素进行概述,以更好地指导临床治疗。     

原发性胃肠道弥漫大B细胞淋巴瘤的预后因素分析

目的 :探讨原发性胃肠道弥漫大B细胞淋巴瘤(PGI-DLBCL)的临床特点、免疫表型及治疗方案与预后的关系。方法:收集我院2000年4月至2014年6月诊治的91例PGI-DLBCL患者的临床资料,对其临床特征、治疗方案、免疫分型以及疗效进行回顾性分析。结果:随访时间为3~166个月,中位随访时间49个月。91例PGI-DLBCL患者中,男女比例为1.22∶1,中位年龄57(17~79)岁。Ann Arbor分期Ⅰ~Ⅱ期49例(53.8%),Ⅲ~Ⅳ期42例(46.2%);血清乳酸脱氢酶(LDH)正常者75例(82.4%),升高者16例(17.6%);国际预后指数(IPI)低/低中危患者73例(80.2%),中/中高危患者18例(19.8%);生发中心B细胞(GCB)患者22例(34.9%),非GCB(non GCB)患者41例(65.1%);采用CHOP(环磷酰胺、长春地辛、表柔比星、甲泼尼龙)方案治疗的55例(60.4%),利妥昔单抗联合CHOP方案化学治疗(化疗)36例(39.6%),5年总生存(OS)率分别为75.5%、95.7%。单因素分析结果显示IPI、Ann Arbor临床分期、LDH水平、免疫分型以及是否联合利妥昔单抗化疗对生存率有显著影响(均P     

老年EB病毒阳性弥漫大B细胞淋巴瘤的研究进展

EB病毒(EBV)是人类疱疹病毒科γ亚科的DNA病毒,也是惟一引起人类感染的淋巴滤泡病毒,有嗜B淋巴细胞特性,90％～95％的成人有血清学感染证据.老年EBV阳性弥漫大B细胞淋巴瘤(DLBCL)又称为年龄相关EBV阳性B细胞增生性疾病,是非霍奇金淋巴瘤中最常见类型,主要发生于50岁以上,无任何免疫缺陷或曾患淋巴瘤的老年患者.2008年版造血与淋巴组织肿瘤WHO分类中,老年EBV阳性DLBCL作为新的类型被单独列出[1].Oyama等[2]检测到DLBCL患者中存在EBV,并发现患病人群年龄较高,无免疫缺陷性疾病,认为年龄相关的免疫系统恶化可与和EBV阳性DLBCL中B淋巴细胞增殖紊乱相关.老年EBV阳性DLBCL亚洲国家发病率为8％ ～ 10％、西方国家为1％ ～3％[3],临床过程为进展性疾病,预后不良.EBV感染可能是本病的一个危险因素,现对EBV感染DLBCL的发病机制等方面的研究进展综述如下.     

R-CHOP方案治疗老年弥漫大B细胞淋巴瘤患者疗效分析

目的:评价R-CHOP方案治疗老年弥漫大B细胞淋巴瘤(DLBCL)患者的疗效及不良反应.方法:观察25例70～86岁DLBCL患者,用R-CHOP方案治疗8疗程,之后用美罗华单药维持(每3个月1次,维持2年);分析化疗的疗效及不良反应.结果:19例达到完全缓解(CR),6例达到部分缓解(PR),无严重的不良反应.12例...     

弥漫大B细胞淋巴瘤预后新指标

弥漫大B 细胞淋巴瘤(DLBCL) 是一种高度异质性的疾病, 临床表现和预后差异较大。经典的预后评价系统 国际预后指数(IPI) 评分是基于年龄、疾病分期和体能状态等简单的临床参数, 由于其自身的局限性和利妥昔单抗 纳入DLBCL 的一线治疗, 经典指标的预后价值存在争议。随着对于DLBCL 认识的深入和新技术的出现, 越来越 多新DLBCL 预后评价指标涌现, 这些新指标的出现将更加有利于丰富和完善DLBCL 的预后评价系统, 以利于更 好的为患者提供精确的诊断分层和个体化治疗。     

弥漫大B细胞淋巴瘤患者治疗前FDG-PET/CT检查与预后的相关性分析

目的:评估治疗前18氟-氟代脱氧葡萄糖-正电子发射计算机断层显像(18F-FDG-PET)/CT的最大标化摄取值(SUVmax)对弥漫大B细胞淋巴瘤(DLBCL)预后预测价值。方法:回顾分析76例新发DLBCL患者初次PET/CT检查中最大SUVmax与疾病分期、乳酸脱氢酶(LDH)、校正国际预后指数(R-IPI)等预后因素之间的相关性以及预后分析。结果:初发DLBL患者PET/CT的SUVmax与疾病分期、B症状、LDH、β2微球蛋白(β2-MG)、美国东部肿瘤协作组(ECOG)评分呈正相关。R-IPI3个预后组中的SUVmax有显著区别,R-IPI预后差的一组SUVmax均值明显高于前2组,有统计学意义(P<10与SUVmax≥10组总有效率分别为87.9%和55.8%(P     

治疗前血浆纤维蛋白原水平在弥漫大B细胞淋巴瘤患者预后判断中的价值

目的:探讨治疗前血浆纤维蛋白原(Fib)水平在初治弥漫大B细胞淋巴瘤(DLBCL)患者预后判断中的价值.方法:回顾性分析符合入选标准的389例初治DLBCL患者治疗前血浆Fib水平与患者临床病理特征及预后的关系.采用受试者工作特征曲线确定治疗前血浆Fib截断值,按截断值将患者分为Fib高水平组(245例)和Fib低水平...     

乙型肝炎病毒感染与弥漫大B细胞淋巴瘤临床、病理及预后的关系

目的探讨乙型肝炎病毒(HBV)感染与弥漫大B细胞淋巴瘤(DLBCL)临床、病理及预后的关系。方法采用酶联免疫吸附试验(ELISA)检测2004年1月至2013年1月该院收治的150例DLBCL患者的乙肝5项和肝功能,并选取同期住院的其他肿瘤患者150例及门诊健康体检者150例作为对照。结果 DLBCL患者乙型肝炎表面抗原(HBs Ag)的阳性率(22.7%)显著高于其他肿瘤组患者(9.3%)和健康对照组(8.0%)(P<0.05)。HBs Ag阳性组及HBs Ag阴性组DLBCL临床分期、肝脾受累、乳酸脱氢酶(LDH)含量、结节外受累区域和国际预后指数评分(IPI)差异具有统计学意义(P<0.05),且二组患者化疗前后肝功能损伤情况比较亦有统计学差异(P<0.05)。HBs Ag阴性组治疗完全缓解率及生存期均显著高于HBs Ag阳性组(P<0.05)。结论 DLBCL患者HBs Ag阳性率显著高于其他恶性肿瘤患者及健康对照,且HBV感染与DLBCL患者临床病理特征及预后相关。     

Prognostic significance of hepatocyte growth factor and c-MET expression in patients with diffuse large B-cell lymphoma

The expression and prognostic significance of hepatocyte growth factor (HGF) and its receptor c-MET (MET proto-oncogene) was analysed in 96 cases of diffuse large B-cell lymphoma (DLBCL). Tissue sections were immunohistochemically stained for HGF and c-Met. The prognosis of HGF-positive and c-Met-positive cases was significantly worse than negative cases (HGF: P = 0.0036; c-Met: P = 0.0002). In addition, in the low-risk international prognostic index group, HGF-negative and c-Met-negative cases had a significantly better prognosis than positive cases (HGF: P = 0.0009; c-Met: P < 0.0001). Our results suggest that HGF/c-MET is a useful clinical marker of prognosis for patients with DLBCL.     

Serum BAFF predicts prognosis better than APRIL in diffuse large B-cell lymphoma patients treated with rituximab plus CHOP chemotherapy

Objectives:  B-cell activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) regulate survival and proliferation of B cells. Thus the association of elevated serum levels of BAFF and APRIL with worse prognosis has been suggested in B-cell lymphoid malignancies. However, the prognostic relevance of BAFF and APRIL is unknown in patients treated with rituximab, a monoclonal antibody targeting B-cell depletion.
Methods:  We measured serum levels of BAFF and APRIL by enzyme-linked immunosorbent assay in 66 patients newly diagnosed as diffuse large B-cell lymphoma (DLBCL). All patients were treated with rituximab-CHOP chemotherapy.
Results:  The mean (±standard deviation) serum level of BAFF (1 970.21 ± 1 979.45 pg/mL) was higher in DLBCL than in controls (861.03 ± 194.92 pg/mL, Mann–Whitney U -test, P  < 0.001). When the patients were dichotomized into high and low BAFF group based on the median value (1 258.00 pg/mL), high BAFF group had less numbers of complete responders to rituximab-CHOP, and more relapses or progression after or during treatment. In multivariate analysis, serum BAFF was an independent prognostic factor for overall survival and progression-free survival ( P  < 0.05). Although serum levels of APRIL was also higher than controls (10.60 ± 19.08 ng/mL vs. 1.10 ± 0.30 ng/mL, P  = 0.023), it failed to show prognostic significance.
Conclusions:  Serum BAFF may be a useful indicator predicting prognosis in DLBCL patients treated with rituximab-containing chemotherapy.     

Primary diffuse large B-cell lymphoma of the uterus: A SEER database analysis

Uterine diffuse large B-cell lymphoma (DLBCL) is a rare clinical condition. Most studies for uterine DLBCL are derived from case reports and series. Our main objective was to present a new case while also investigating the demographic, clinical characteristics, and survival of women with primary uterine DLBCL as compared to non-uterine DLBCL using the Surveillance, Epidemiology, and End Results incidence database. We queried the Surveillance, Epidemiology, and End Results database for women aged 18 years or older with a diagnosis of primary DLBCL from 1975 to 2017. The most common site of primary uterine DLBCL is the cervix uteri not otherwise specified, followed by endometrium, uterus not otherwise specified, corpus uteri, myometrium and isthmus uteri. Non-uterine DLBCL cases tend to be older than uterine DLBCL cases. Uterine DLBCL is most common among women aged 40 to 64 years. Patients with uterine DLBCL showed greater survival than non-uterine DLBCL patients, and patients treated in the rituximab era also exhibited a survival benefit. Both the elderly and African American cohorts experienced worse overall survival.     

Recent advances in the understanding and management of diffuse large B-cell lymphoma in children

Diffuse large B-cell lymphomas (DLBCL) are neoplasms of transformed mature B cells, accounting for approximately 10% of non-Hodgkin lymphomas (NHL) of childhood. Increasing evidence indicates that DLBCL are composed of biologically distinct subsets. Clinical features of children with DLBCL differ from those with other NHL entities, e.g. by a lower frequency of bone-marrow and central nervous sytem involvement. Treatment strategies originally designed for Burkitt lymphoma appear to be efficacious for children with DLBCL. However, children with primary mediastinal large B-cell lymphoma may need a more specific treatment approach, given their inferior outcome in recent studies. The addition of the monoclonal anti-CD20 antibody rituximab to standard CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy improved outcome of adults with DLBCL significantly. However, preliminary data suggest differences between DLBCL of children and adults concerning cell of origin, genetic abnormalities and responsiveness to current treatments. Thus, the potential role of monoclonal antibodies in the treatment of children with DLBCL remains to be determined. The availability of new methodological tools, such as gene expression profiling, will greatly enhance our insights into the biology of childhood DLBCL and its similarities and disparities compared to adult DLBCL. Furthermore, these tools may enable a more risk-adapted and rationally targeted subtype-specific therapy in the future.     

De novo CD5-positive diffuse large B-cell lymphoma: clinical characteristics and therapeutic outcome

To determine the clinical significance of CD5 expression in diffuse large B-cell lymphoma (DLBL) without a clinical history of low-grade B-cell lymphoma, we have reviewed the clinical features and therapeutic outcome of 25 patients with de novo CD5-positive DLBL, and compared the results with those of 87 patients with CD5-negative DLBL and 22 patients with mantle cell lymphoma (MCL). The patients with de novo CD5-positive DLBL had clinical characteristics of elderly onset (median age 63, range 37-91), and female predominance (male/female 10/15). 21 (84%) of these patients had extranodal involvement at presentation, with great variation in the sites. In comparison with the patients with CD5-negative DLBL, the treatment outcome for the patients with de novo CD5-positive DLBL was very poor with frequent relapse. The failure-free survival curve was almost identical to that of patients with MCL, showing that standard chemotherapy for DLBL was not effective for most of the patients with de novo CD5-positive DLBL. These findings suggest that de novo CD5-positive DLBL forms a distinct subgroup of DLBL.     

Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms

This study was undertaken to further elucidate the biological mechanisms underlying the frequent event of transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL). The gene expression profiles of 20 paired lymph node biopsies, derived from the same patient pre- and post-transformation, were analysed using the Lymphochip cDNA microarray. TP53 mutation analysis was performed and copy number alterations at the c-REL and CDNK2A examined. Immunohistochemistry was performed on an independent panel of paired transformation paraffin-embedded samples. Transformed follicular lymphoma was predominantly of the germinal centre B-like phenotype both at the mRNA and protein level. Despite this homogeneity, transformation proceeded by at least two pathways. One mechanism was characterised by high proliferation, as assessed by the co-ordinately expressed genes of the proliferation signature. This group was associated with the presence of recurrent oncogenic abnormalities. In the remaining cases, proliferation was not increased and transformation proceeded by alternative routes as yet undetermined. Genes involved in cellular proliferation prevailed amongst those that were significantly increased upon transformation and T cell and follicular dendritic-associated genes predominated amongst those that decreased. t-FL is a germinal centre B (GCB)-like malignancy that evolves by two pathways, one that is similar in proliferation rate to the antecedent FL and the other that has a higher proliferation rate and is characterised by the presence of recognised oncogenic abnormalities.     

Profiling of diffuse large B-cell lymphoma by immunohistochemistry: identification of prognostic subgroups

Diffuse large B-cell lymphoma (DLBCL) is a frequent lymphoma subtype with a heterogeneous behavior and a variable response to conventional chemotherapy. This clinical diversity is believed to reflect differences in the molecular pathways leading to lymphomagenesis. In this study, we have analyzed pretreatment, diagnostic samples from 108 DLBCL by immunohistology for expression of four markers linked to germinal center B-cells (CD10, Bcl-6), postgerminal center B-cells (MUM1) and apoptosis (Bcl-2). The results indicate that both CD10 and Bcl-6 are favorable prognostic indicators, in contrast to Bcl-2, which is an adverse parameter. Furthermore, using two algorithms for distinction between low- and high-risk patients proposed by Hans et al. (Blood, 2004; 103:275) and Muris et al. (Journal of Pathology, 2006; 208:714), it is shown that both are useful for predicting outcome in DLBCL. However, in this report, the algorithm of Hans et al. was superior to that of Muris et al. These findings confirm and extend other studies and indicate that different prognostic subgroups of DLBCL can be distinguished by simple immunohistological investigations for a limited number of markers. Whether these groups are also relevant for individual treatment decisions will be important to investigate in prospective studies.     

双侧卵巢非霍奇金淋巴瘤弥漫大B细胞型2例

1病历资料例1.女,57岁,以"下腹胀痛、尿频、食欲不振1个月余为主诉"于2008-04-14就诊我院妇产科,拟诊为多发子宫肌瘤。行"经腹全子宫及双附件切除术+病灶切除术"后病理检查诊断双侧卵巢非霍奇金淋巴瘤。住我院血液科,予以CHOP(氟美松10 mg,每日1次静脉滴注,连用